Next-Generation Strategies for Neural Repair and Regeneration: Neural Organoid Transplantation in the CNS

Abstract

Neurological disorders are often devastating and notoriously difficult to repair, creating an urgent need for novel research models and therapeutic strategies. Neural organoids—three-dimensional, self-assembling structures derived from stem cells—have emerged as a powerful platform to address this challenge. Supported by enabling technologies like bioreactors and 3D printing, advanced maturation protocols have significantly enhanced their cellular diversity and functional utility. This progress has paved the way for their widespread application in developmental studies, disease modelling, and notably, regenerative medicine. Focusing specifically on the latter, this article reviews how neural organoid transplantation opens new avenues for treating CNS injuries and degeneration. We first elaborate on the development, characteristics, and maturation strategies of neural organoids. We then summarise the translational applications and achievements of transplanting both whole neural organoids and their derived vesicles, analyse the prevailing challenges in the field, and finally, outline future directions to advance the therapeutic potential of this technology.

Keywords

characteristics / maturation / neural organoids / repair and regeneration / transplantation

References

[1] C. Zivko, R. Sagar, A. Xydia, et al., “iPSC-Derived Hindbrain Organoids to Evaluate Escitalopram Oxalate Treatment Responses Targeting Neuropsychiatric Symptoms in Alzheimer's Disease,” Molecular Psychiatry 29, no. 11 (2024): 3644–3652.

[2] T. Fang, H. Zhang, Y. Xie, et al., “Centimeter-Scale Self-Assembling Tendon Organoids Drive Tissue Regeneration,” Advanced Science 12 (2025): e09453.

[3] S. E. Spirig and M. Renner, “Toward Retinal Organoids in High-Throughput,” Cold Spring Harbor Perspectives in Medicine 14, no. 3 (2024): a041275.

[4] C. S. Cowan, M. Renner, M. De Gennaro, et al., “Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution,” Cell 182, no. 6 (2020): 1623–1640.e34.

[5] D. Di Lisa, A. Andolfi, G. Masi, et al., “Impact of Perfusion on Neuronal Development in Human Derived Neuronal Networks,” APL Bioengineering 8, no. 4 (2024): 046102.

[6] D. N. A. Suong, K. Imamura, I. Inoue, et al., “Induction of Inverted Morphology in Brain Organoids by Vertical-Mixing Bioreactors,” Communications Biology 4, no. 1 (2021): 1213.

[7] S. Y. Tan, X. Feng, L. K. W. Cheng, and A. R. Wu, “Vascularized Human Brain Organoid On-Chip,” Lab on a Chip 23, no. 12 (2023): 2693–2709.

[8] Y. Huang, T. Liu, Q. Huang, and Y. Wang, “From Organ-on-a-Chip to Human-on-a-Chip: A Review of Research Progress and Latest Applications,” ACS Sensors 9, no. 7 (2024): 3466–3488.

[9] P. J. Obeid, P. Yammine, H. El-Nakat, et al., “Organ-on-a-Chip Devices: Technology Progress and Challenges,” ChemBioChem: A European Journal of Chemical Biology 25, no. 23 (2024): e202400580.

[10] D. Patel, S. Shetty, C. Acha, et al., “Microinstrumentation for Brain Organoids,” Advanced Healthcare Materials 13, no. 21 (2024): e2302456.

[11] M. A. Cadena, A. Sing, K. Taylor, et al., “A 3D Bioprinted Cortical Organoid Platform for Modeling Human Brain Development,” Advanced Healthcare Materials 13, no. 27 (2024): e2401603.

[12] Y. Yan, X. Li, Y. Gao, et al., “3D Bioprinting of Human Neural Tissues With Functional Connectivity,” Cell Stem Cell 31, no. 2 (2024): 260–274.e7.

[13] P. Asadi Sarabi, M. Shabanpouremam, A. R. Eghtedari, et al., “AI-Based Solutions for Current Challenges in Regenerative Medicine,” European Journal of Pharmacology 984 (2024): 177067.

[14] L. Bai, Y. Wu, G. Li, W. Zhang, H. Zhang, and J. Su, “AI-Enabled Organoids: Construction, Analysis, and Application,” Bioactive Materials 31 (2024): 525–548.

[15] T. van der Molen, A. Spaeth, M. Chini, et al., “Preconfigured Neuronal Firing Sequences in Human Brain Organoids,” Nature Neuroscience 29 (2025): 123–135.

[16] H. Zhu, C. Yao, Z. Xu, et al., “Recent Advances in 3D Models of the Nervous System for Neural Regeneration Research and Drug Development,” Acta Biomaterialia 202 (2025): 1–26.

[17] Y. Yin, D. Su, J. S. T. Lam, and T. Feng, “Advances in Clinical Neurorestorative Treatments of Parkinson's Disease,” Journal of Neurorestoratology 13, no. 3 (2025): 100204.

[18] Y. Zhao, S. Li, L. Zhu, et al., “Personalized Drug Screening Using Patient-Derived Organoid and Its Clinical Relevance in Gastric Cancer,” Cell Reports Medicine 5, no. 7 (2024): 101627.

[19] Q. Yao, S. Cheng, Q. Pan, et al., “Organoids: Development and Applications in Disease Models, Drug Discovery, Precision Medicine, and Regenerative Medicine,” MedComm (2020) 5, no. 10 (2024): e735.

[20] S. Vijayavenkataraman, W. C. Yan, W. F. Lu, C. H. Wang, and J. Y. H. Fuh, “3D Bioprinting of Tissues and Organs for Regenerative Medicine,” Advanced Drug Delivery Reviews 132 (2018): 296–332.

[21] H. Liu, S. S. Huang, G. Lingam, D. Kai, X. Su, and Z. Liu, “Advances in Retinal Pigment Epithelial Cell Transplantation for Retinal Degenerative Diseases,” Stem Cell Research & Therapy 15, no. 1 (2024): 390.

[22] J. Pardieck and S. Sakiyama-Elbert, “Genome Engineering for CNS Injury and Disease,” Current Opinion in Biotechnology 52 (2018): 89–94.

[23] C. E. Dorrier, H. E. Jones, L. Pintarić, J. A. Siegenthaler, and R. Daneman, “Emerging Roles for CNS Fibroblasts in Health, Injury and Disease,” Nature Reviews. Neuroscience 23, no. 1 (2022): 23–34.

[24] R. Rust, L. R. Nih, L. Liberale, et al., “Brain Repair Mechanisms After Cell Therapy for Stroke,” Brain 147, no. 10 (2024): 3286–3305.

[25] H. Li, C. Guan, D. Fang, et al., “Research Hotspots and Global Trends in Transcranial Magnetic Stimulation for Stroke Neurorestoration: A 30-Year Bibliometric Analysis,” Journal of Neurorestoratology 13, no. 1 (2025): 100148.

[26] V. O'Connor, R. Shura, P. Armistead-Jehle, and D. B. Cooper, “Neuropsychological Evaluation in Traumatic Brain Injury,” Physical Medicine and Rehabilitation Clinics of North America 35, no. 3 (2024): 593–605.

[27] Q. Zhou, W. Shen, and L. Wen, “Advances in Clinical Neurorestorative Treatments in Brain Trauma,” Journal of Neurorestoratology 13, no. 3 (2025): 100191.

[28] G. Han, N. S. Lavoie, N. Patil, et al., “3D-Printed Scaffolds Promote Enhanced Spinal Organoid Formation for Use in Spinal Cord Injury,” Advanced Healthcare Materials 14 (2025): e04817.

[29] B. Tao, J. Pei, H. Li, et al., “Inhibition of P2X7R Alleviates Neuroinflammation and Brain Edema After Traumatic Brain Injury by Suppressing the NF-κB/NLRP3 Inflammasome Pathway,” Journal of Neurorestoratology 12, no. 2 (2024): 100106.

[30] S. Shaikh, L. Siddique, H. T. Khalifey, et al., “Brain Organoid Model Systems of Neurodegenerative Diseases: Recent Progress and Future Prospects,” Frontiers in Neuroscience 19 (2025): 1604435.

[31] R. E. Handsaker, S. Kashin, N. M. Reed, et al., “Long Somatic DNA-Repeat Expansion Drives Neurodegeneration in Huntington's Disease,” Cell 188, no. 3 (2025): 623–639.e19.

[32] S. Williams, S. D. Relton, H. Fang, et al., “Supervised Classification of Bradykinesia in Parkinson's Disease From Smartphone Videos,” Artificial Intelligence in Medicine 110 (2020): 101966.

[33] R. Marcus, “What Is Multiple Sclerosis?,” Journal of the American Medical Association 328, no. 20 (2022): 2078.

[34] H. K. Hopkins, E. M. Traverse, and K. L. Barr, “Methodologies for Generating Brain Organoids to Model Viral Pathogenesis in the CNS,” Pathogens 10, no. 11 (2021): 1510.

[35] S. Padmakumar, A. D'Souza, N. N. Parayath, B. S. Bleier, and M. M. Amiji, “Nucleic Acid Therapies for CNS Diseases: Pathophysiology, Targets, Barriers, and Delivery Strategies,” Journal of Controlled Release 352 (2022): 121–145.

[36] M. S. Yekaninejad, N. Derakhshanrad, E. Kazemi, A. Derakhshanrad, and H. Saberi, “Influential Factors for Final Neurorehabilitation Outcome Scores in Patients With Spinal Cord Injury: A Longitudinal Cohort Study,” Journal of Neurorestoratology 12, no. 2 (2024): 100117.

[37] R. Sharma, C. R. M. Oyagawa, H. Abbasi, M. Dragunow, and D. Conole, “Phenotypic Approaches for CNS Drugs,” Trends in Pharmacological Sciences 45, no. 11 (2024): 997–1017.

[38] J. W. Adams, F. R. Cugola, and A. R. Muotri, “Brain Organoids as Tools for Modeling Human Neurodevelopmental Disorders,” Physiology 34, no. 5 (2019): 365–375.

[39] C. A. Trujillo and A. R. Muotri, “Brain Organoids and the Study of Neurodevelopment,” Trends in Molecular Medicine 24, no. 12 (2018): 982–990.

[40] A. V. Eremeev, O. S. Lebedeva, M. E. Bogomiakova, M. A. Lagarkova, and A. N. Bogomazova, “Cerebral Organoids-Challenges to Establish a Brain Prototype,” Cells 10, no. 7 (2021): 1790.

[41] A. O. Ajongbolo and S. A. Langhans, “Brain Organoids and Assembloids-From Disease Modeling to Drug Discovery,” Cells 14, no. 11 (2025): 842.

[42] K. W. Kelley and S. P. Pașca, “Human Brain Organogenesis: Toward a Cellular Understanding of Development and Disease,” Cell 185, no. 1 (2022): 42–61.

[43] C. Corrò, L. Novellasdemunt, and V. S. W. Li, “A Brief History of Organoids,” American Journal of Physiology. Cell Physiology 319, no. 1 (2020): C151–C165.

[44] H. V. Wilson, “A New Method by Which Sponges May be Artificially Reared,” Science 25, no. 649 (1907): 912–915.

[45] J. A. Thomson, J. Itskovitz-Eldor, S. S. Shapiro, et al., “Embryonic Stem Cell Lines Derived From Human Blastocysts,” Science 282, no. 5391 (1998): 1145–1147.

[46] S.-C. Zhang, M. Wernig, I. D. Duncan, O. Brüstle, and J. A. Thomson, “In Vitro Differentiation of Transplantable Neural Precursors From Human Embryonic Stem Cells,” Nature Biotechnology 19, no. 12 (2001): 1129–1133.

[47] Y. Elkabetz, G. Panagiotakos, G. Al Shamy, N. D. Socci, V. Tabar, and L. Studer, “Human ES Cell-Derived Neural Rosettes Reveal a Functionally Distinct Early Neural Stem Cell Stage,” Genes & Development 22, no. 2 (2008): 152–165.

[48] K. Takahashi and S. Yamanaka, “Induction of Pluripotent Stem Cells From Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors,” Cell 126, no. 4 (2006): 663–676.

[49] M. Eiraku, K. Watanabe, M. Matsuo-Takasaki, et al., “Self-Organized Formation of Polarized Cortical Tissues From ESCs and Its Active Manipulation by Extrinsic Signals,” Cell Stem Cell 3, no. 5 (2008): 519–532.

[50] M. A. Lancaster, M. Renner, C. A. Martin, et al., “Cerebral Organoids Model Human Brain Development and Microcephaly,” Nature 501, no. 7467 (2013): 373–379.

[51] D. Jgamadze, J. T. Lim, Z. Zhang, et al., “Structural and Functional Integration of Human Forebrain Organoids With the Injured Adult Rat Visual System,” Cell Stem Cell 30, no. 2 (2023): 137–152.e7.

[52] H. Shimada, Y. Sato, T. Sasaki, et al., “A Next-Generation iPSC-Derived Forebrain Organoid Model of Tauopathy With Tau Fibrils by AAV-Mediated Gene Transfer,” Cell Reports Methods 2, no. 9 (2022): 100289.

[53] L. Muok, C. Liu, X. Chen, et al., “Inflammatory Response and Exosome Biogenesis of Choroid Plexus Organoids Derived From Human Pluripotent Stem Cells,” International Journal of Molecular Sciences 24, no. 8 (2023): 7660.

[54] T. Zhao, L. Pellegrini, B. van der Hee, et al., “Choroid Plexus Organoids Reveal Mechanisms of Streptococcus suis Translocation at the Blood-Cerebrospinal Fluid Barrier,” Fluids and Barriers of the CNS 22, no. 1 (2025): 14.

[55] M. A. Lancaster, N. S. Corsini, S. Wolfinger, et al., “Guided Self-Organization and Cortical Plate Formation in Human Brain Organoids,” Nature Biotechnology 35, no. 7 (2017): 659–666.

[56] B.-Q. Lai, B. Feng, M.-T. Che, et al., “A Modular Assembly of Spinal Cord–Like Tissue Allows Targeted Tissue Repair in the Transected Spinal Cord,” Advanced Science 5, no. 9 (2018): 1800261.

[57] M. N. Vergara, M. Flores-Bellver, S. Aparicio-Domingo, et al., “Three-Dimensional Automated Reporter Quantification (3D-ARQ) Technology Enables Quantitative Screening in Retinal Organoids,” Development 144, no. 20 (2017): 3698–3705.

[58] S. Velasco, A. J. Kedaigle, S. K. Simmons, et al., “Individual Brain Organoids Reproducibly Form Cell Diversity of the Human Cerebral Cortex,” Nature 570, no. 7762 (2019): 523–527.

[59] Z. He, L. Dony, J. S. Fleck, et al., “An Integrated Transcriptomic Cell Atlas of Human Neural Organoids,” Nature 635, no. 8039 (2024): 690–698.

[60] K. Kiaee, Y. A. Jodat, N. J. Bassous, N. Matharu, and S. R. Shin, “Transcriptomic Mapping of Neural Diversity, Differentiation and Functional Trajectory in iPSC-Derived 3D Brain Organoid Models,” Cells 10, no. 12 (2021): 3422.

[61] J. G. Camp, F. Badsha, M. Florio, et al., “Human Cerebral Organoids Recapitulate Gene Expression Programs of Fetal Neocortex Development,” Proceedings of the National Academy of Sciences of the United States of America 112, no. 51 (2015): 15672–15677.

[62] X. Zhao, V. Mouilleau, Y. Wang, et al., “PCM1 Coordinates Centrosome Asymmetry With Polarized Endosome Dynamics to Regulate Daughter Cell Fate,” Nature Communications 16, no. 1 (2025): 10728.

[63] X. Wu, K. Zhang, N. Kuang, et al., “Developing Brain Asymmetry Shapes Cognitive and Psychiatric Outcomes in Adolescence,” Nature Communications 16, no. 1 (2025): 4480.

[64] G. Yu, Z. Liu, X. Wu, et al., “Common and Disorder-Specific Cortical Thickness Alterations in Internalizing, Externalizing and Thought Disorders During Early Adolescence: An Adolescent Brain and Cognitive Development Study,” Journal of Psychiatry & Neuroscience 48, no. 5 (2023): E345.

[65] H. Fan, Z. Liu, X. Wu, et al., “Decoding Anxiety-Impulsivity Subtypes in Preadolescent Internalising Disorders: Findings From the Adolescent Brain Cognitive Development Study,” British Journal of Psychiatry 223, no. 6 (2023): 542–554.

[66] N. Kuang, Z. Liu, G. Yu, et al., “Neurodevelopmental Risk and Adaptation as a Model for Comorbidity Among Internalizing and Externalizing Disorders: Genomics and Cell-Specific Expression Enriched Morphometric Study,” BMC Medicine 21, no. 1 (2023): 291.

[67] D. Reis de Assis, A. B. Pentz, J. Requena Osete, et al., “Investigating Neural Impairments in Psychotic Disorders Using Electroencephalography and Cortical Spheroids,” Translational Psychiatry 16, no. 1 (2026): 114.

[68] M. Notaras, A. Lodhi, F. Dündar, et al., “Schizophrenia Is Defined by Cell-Specific Neuropathology and Multiple Neurodevelopmental Mechanisms in Patient-Derived Cerebral Organoids,” Molecular Psychiatry 27, no. 3 (2022): 1416–1434.

[69] Y. Sasai, “Cytosystems Dynamics in Self-Organization of Tissue Architecture,” Nature 493, no. 7432 (2013): 318–326.

[70] A. Jain, G. Gut, F. Sanchis-Calleja, et al., “Morphodynamics of Human Early Brain Organoid Development,” bioRxiv (2023): 2023.08.21.553827.

[71] A. Mousley, R. A. I. Bethlehem, F. C. Yeh, and D. E. Astle, “Topological Turning Points Across the Human Lifespan,” Nature Communications 16, no. 1 (2025): 10055.

[72] S. A. Sloan, J. Andersen, A. M. Pașca, F. Birey, and S. P. Pașca, “Generation and Assembly of Human Brain Region-Specific Three-Dimensional Cultures,” Nature Protocols 13, no. 9 (2018): 2062–2085.

[73] L. Sarrafha, G. M. Parfitt, R. Reyes, et al., “High-Throughput Generation of Midbrain Dopaminergic Neuron Organoids From Reporter Human Pluripotent Stem Cells,” STAR Protocols 2, no. 2 (2021): 100463.

[74] F. R. Kiral, B. Cakir, Y. Tanaka, et al., “Generation of Ventralized Human Thalamic Organoids With Thalamic Reticular Nucleus,” Cell Stem Cell 30, no. 5 (2023): 677–688.e5.

[75] T. Kamei, A. Tamada, T. Kimura, A. Kakizuka, A. Asai, and K. Muguruma, “Survival and Process Outgrowth of Human iPSC-Derived Cells Expressing Purkinje Cell Markers in a Mouse Model for Spinocerebellar Degenerative Disease,” Experimental Neurology 369 (2023): 114511.

[76] J. Xu, S. Fang, S. Deng, et al., “Generation of Neural Organoids for Spinal-Cord Regeneration via the Direct Reprogramming of Human Astrocytes,” Nature Biomedical Engineering 7, no. 3 (2023): 253–269.

[77] J. H. Lee, H. Shin, M. R. Shaker, et al., “Production of Human Spinal-Cord Organoids Recapitulating Neural-Tube Morphogenesis,” Nature Biomedical Engineering 6, no. 4 (2022): 435–448.

[78] W. Pang, J. Zhu, K. Yang, et al., “Generation of Human Region-Specific Brain Organoids With Medullary Spinal Trigeminal Nuclei,” Cell Stem Cell 31, no. 10 (2024): 1501–1512.e8.

[79] Y. Shi, L. Sun, M. Wang, et al., “Vascularized Human Cortical Organoids (vOrganoids) Model Cortical Development In Vivo,” PLoS Biology 18, no. 5 (2020): e3000705.

[80] M. Nishimura, S. Adachi, T. Kodera, A. Y. Sato, R. F. Takeuchi, and F. Osakada, “Thalamus-Cortex Interactions Drive Cell Type-Specific Cortical Development in Human Pluripotent Stem Cell-Derived Assembloids,” Proceedings of the National Academy of Sciences of the United States of America 122, no. 47 (2025): e2506573122.

[81] A. E. Stanton, A. Bubnys, E. Agbas, et al., “Engineered 3D Immuno-Glial-Neurovascular Human miBrain Model,” Proceedings of the National Academy of Sciences of the United States of America 122, no. 42 (2025): e2511596122.

[82] X. Liang, L. Sun, M. Xia, et al., “Dissecting Human Cortical Similarity Networks Across the Lifespan,” Neuron 113, no. 19 (2025): 3275–3295.e11.

[83] A. Jourdon, F. Wu, J. Mariani, et al., “Modeling Idiopathic Autism in Forebrain Organoids Reveals an Imbalance of Excitatory Cortical Neuron Subtypes During Early Neurogenesis,” Nature Neuroscience 26, no. 9 (2023): 1505–1515.

[84] J. O. de Jong, C. Llapashtica, M. Genestine, et al., “Cortical Overgrowth in a Preclinical Forebrain Organoid Model of CNTNAP2-Associated Autism Spectrum Disorder,” Nature Communications 12, no. 1 (2021): 4087.

[85] E. Frattini, G. Faustini, G. Lopez, et al., “Lewy Pathology Formation in Patient-Derived GBA1 Parkinson's Disease Midbrain Organoids,” Brain 148, no. 4 (2025): 1242–1257.

[86] H. Cai, C. Tian, L. Chen, et al., “Vascular Network-Inspired Diffusible Scaffolds for Engineering Functional Midbrain Organoids,” Cell Stem Cell 32, no. 5 (2025): 824–837.e5.

[87] I. Pavlinov, M. Tambe, J. Abbott, et al., “In Depth Characterization of Midbrain Organoids Derived From Wild Type iPSC Lines,” PLoS One 18, no. 10 (2023): e0292926.

[88] G. Gomez-Giro, D. Frangenberg, D. Vega, et al., “α-Synuclein Pathology Spreads in a Midbrain-Hindbrain Assembloid Model,” Advanced Science 12, no. 20 (2025): e2409040.

[89] P. Valiulahi, V. Vidyawan, L. Puspita, et al., “Generation of Caudal-Type Serotonin Neurons and Hindbrain-Fate Organoids From hPSCs,” Stem Cell Reports 16, no. 8 (2021): 1938–1952.

[90] A. Atamian, M. Birtele, N. Hosseini, et al., “Human Cerebellar Organoids With Functional Purkinje Cells,” Cell Stem Cell 31, no. 1 (2024): 39–51.e6.

[91] A. Atamian, M. Birtele, N. Hosseini, and G. Quadrato, “Generation and Long-Term Culture of Human Cerebellar Organoids From Pluripotent Stem Cells,” Nature Protocols 20, no. 6 (2025): 1584–1615.

[92] Y. Chen, L. A. Bury, F. Chen, K. A. Aldinger, H. C. Miranda, and A. Wynshaw-Boris, “Generation of Advanced Cerebellar Organoids for Neurogenesis and Neuronal Network Development,” Human Molecular Genetics 32, no. 18 (2023): 2832–2841.

[93] J. Brás, D. Henriques, R. Moreira, et al., “Establishment and Characterization of Human Pluripotent Stem Cells-Derived Brain Organoids to Model Cerebellar Diseases,” Scientific Reports 12, no. 1 (2022): 12513.

[94] M. Ikeda, D. Doi, H. Ebise, et al., “Validation of Non-Destructive Morphology-Based Selection of Cerebral Cortical Organoids by Paired Morphological and Single-Cell RNA-Seq Analyses,” Stem Cell Reports 19, no. 11 (2024): 1635–1646.

[95] A. Bhaduri, M. G. Andrews, W. Mancia Leon, et al., “Cell Stress in Cortical Organoids Impairs Molecular Subtype Specification,” Nature 578, no. 7793 (2020): 142–148.

[96] C. Cheroni, S. Trattaro, N. Caporale, et al., “Benchmarking Brain Organoid Recapitulation of Fetal Corticogenesis,” Translational Psychiatry 12, no. 1 (2022): 520.

[97] Y. Wu, J. Cheng, J. Qi, et al., “Three-Dimensional Liquid Metal-Based Neuro-Interfaces for Human Hippocampal Organoids,” Nature Communications 15, no. 1 (2024): 4047.

[98] Y. Xiang, Y. Tanaka, B. Cakir, et al., “hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused With Cortical Organoids,” Cell Stem Cell 24, no. 3 (2019): 487–497.e7.

[99] D. Shin, C. N. Kim, J. Ross, et al., “Thalamocortical Organoids Enable In Vitro Modeling of 22q11.2 Microdeletion Associated With Neuropsychiatric Disorders,” Cell Stem Cell 31, no. 3 (2024): 421–432.e8.

[100] R. Matsumoto, H. Suga, Y. Takahashi, T. Aoi, and T. Yamamoto, “Prediction of the Hypothalamus-Pituitary Organoid Formation Using Machine Learning,” Cell Reports Methods 5, no. 8 (2025): 101119.

[101] L. Sarrafha, D. R. Neavin, G. M. Parfitt, et al., “Novel Human Pluripotent Stem Cell-Derived Hypothalamus Organoids Demonstrate Cellular Diversity,” iScience 26, no. 9 (2023): 107525.

[102] A. Ozgun, D. J. Lomboni, A. Aylsworth, et al., “Unraveling the Assembloid: Real-Time Monitoring of Dopaminergic Neurites in an Inter-Organoid Pathway Connecting Midbrain and Striatal Regions,” Materials Today Bio 25 (2024): 100992.

[103] Y. Miura, M. Y. Li, F. Birey, et al., “Generation of Human Striatal Organoids and Cortico-Striatal Assembloids From Human Pluripotent Stem Cells,” Nature Biotechnology 38, no. 12 (2020): 1421–1430.

[104] X. Chen, H. Saiyin, Y. Liu, et al., “Human Striatal Organoids Derived From Pluripotent Stem Cells Recapitulate Striatal Development and Compartments,” PLoS Biology 20, no. 11 (2022): e3001868.

[105] L. H. Chew, E. Mercier, J. C. Rogalski, S. Pippard, and E. Knock, “Methods to Extract and Analyze Fluid From Human Pluripotent Stem Cell-Derived Choroid Plexus Organoids,” Frontiers in Molecular Neuroscience 16 (2023): 1243499.

[106] H. Sasaki, H. Suga, K. Takeuchi, et al., “Subcutaneous Transplantation of Human Embryonic Stem Cells-Derived Pituitary Organoids,” Frontiers in Endocrinology 14 (2023): 1130465.

[107] S. Wang, D. Jiang, Y. Xiao, et al., “Human Pituitary Organoids: Transcriptional Landscape Deciphered by scRNA-Seq and Stereo-Seq, With Insights Into SOX3's Role in Pituitary Development,” Advanced Science 12, no. 14 (2025): e2414230.

[108] H. Gao, Y. Zeng, X. Huang, et al., “Extracellular Vesicles From Organoid-Derived Human Retinal Progenitor Cells Prevent Lipid Overload-Induced Retinal Pigment Epithelium Injury by Regulating Fatty Acid Metabolism,” Journal of Extracellular Vesicles 13, no. 1 (2024): e12401.

[109] J. Harkin, K. H. Peña, C. Gomes, et al., “A Highly Reproducible and Efficient Method for Retinal Organoid Differentiation From Human Pluripotent Stem Cells,” Proceedings of the National Academy of Sciences of the United States of America 121, no. 25 (2024): e2317285121.

[110] S. Lee, W. G. Chung, H. Jeong, et al., “Electrophysiological Analysis of Retinal Organoid Development Using 3D Microelectrodes of Liquid Metals,” Advanced Materials 36, no. 35 (2024): e2404428.

[111] N. K. Mullin, L. R. Bohrer, A. P. Voigt, et al., “NR2E3 Loss Disrupts Photoreceptor Cell Maturation and Fate in Human Organoid Models of Retinal Development,” Journal of Clinical Investigation 134, no. 11 (2024): e173892.

[112] X. Chen, C. Liu, G. McDaniel, et al., “Viscoelasticity of Hyaluronic Acid Hydrogels Regulates Human Pluripotent Stem Cell-Derived Spinal Cord Organoid Patterning and Vascularization,” Advanced Healthcare Materials 13, no. 32 (2024): e2402199.

[113] W. H. Chooi, C. Y. Ng, V. Ow, et al., “Defined Alginate Hydrogels Support Spinal Cord Organoid Derivation, Maturation, and Modeling of Spinal Cord Diseases,” Advanced Healthcare Materials 12, no. 9 (2023): e2202342.

[114] J. P. Licata, K. H. Schwab, Y. E. Har-El, J. A. Gerstenhaber, and P. I. Lelkes, “Bioreactor Technologies for Enhanced Organoid Culture,” International Journal of Molecular Sciences 24, no. 14 (2023): 11427.

[115] M. A. Lancaster and J. A. Knoblich, “Generation of Cerebral Organoids From Human Pluripotent Stem Cells,” Nature Protocols 9, no. 10 (2014): 2329–2340.

[116] E. Gabriel and J. Gopalakrishnan, “Generation of Ipsc-Derived Human Brain Organoids to Model Early Neurodevelopmental Disorders,” Journal of Visualized Experiments 2017, no. 122 (2017): 55372.

[117] J. Z. Kiss, C. Wolverton, S. E. Wyatt, K. H. Hasenstein, and J. J. W. A. van Loon, “Comparison of Microgravity Analogs to Spaceflight in Studies of Plant Growth and Development,” Frontiers in Plant Science 10 (2019): 1577.

[118] T. DiStefano, H. Y. Chen, C. Panebianco, et al., “Accelerated and Improved Differentiation of Retinal Organoids From Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors,” Stem Cell Reports 10, no. 1 (2018): 300–313.

[119] A. Eremeev, L. Belikova, E. Ruchko, et al., “Brain Organoid Generation From Induced Pluripotent Stem Cells in Home-Made Mini Bioreactors,” Journal of Visualized Experiments 178 (2021): e62987.

[120] X. Qian, F. Jacob, M. M. Song, H. N. Nguyen, H. Song, and G. L. Ming, “Generation of Human Brain Region-Specific Organoids Using a Miniaturized Spinning Bioreactor,” Nature Protocols 13, no. 3 (2018): 565–580.

[121] P. Saglam-Metiner, U. Devamoglu, Y. Filiz, et al., “Spatio-Temporal Dynamics Enhance Cellular Diversity, Neuronal Function and Further Maturation of Human Cerebral Organoids,” Communications Biology 6, no. 1 (2023): 173.

[122] S. Charles, E. Jackson-Holmes, G. Sun, et al., “Non-Invasive Quality Control of Organoid Cultures Using Mesofluidic CSTR Bioreactors and High-Content Imaging,” Advanced Materials Technologies 10, no. 3 (2025): 2400473.

[123] H. Cai, Z. Ao, Z. Wu, S. Song, K. Mackie, and F. Guo, “Intelligent Acoustofluidics Enabled Mini-Bioreactors for Human Brain Organoids,” Lab on a Chip 21, no. 11 (2021): 2194–2205.

[124] S.-M. Kang, “Recent Advances in Microfluidic-Based Microphysiological Systems,” BioChip Journal 16, no. 1 (2022): 13–26.

[125] A. G. Monteduro, S. Rizzato, G. Caragnano, A. Trapani, G. Giannelli, and G. Maruccio, “Organs-on-Chips Technologies—A Guide From Disease Models to Opportunities for Drug Development,” Biosensors & Bioelectronics 231 (2023): 115271.

[126] S. G. Uzel, O. C. Amadi, T. M. Pearl, R. T. Lee, P. T. So, and R. D. Kamm, “Simultaneous or Sequential Orthogonal Gradient Formation in a 3D Cell Culture Microfluidic Platform,” Small 12, no. 5 (2016): 612–622.

[127] C. J. Demers, P. Soundararajan, P. Chennampally, et al., “Development-On-Chip: In Vitro Neural Tube Patterning With a Microfluidic Device,” Development 143, no. 11 (2016): 1884–1892.

[128] A. Abdulla, S. Chen, Z. Chen, et al., “Three-Dimensional Microfluidics With Dynamic Fluidic Perturbation Promotes Viability and Uniformity of Human Cerebral Organoids,” Biosensors & Bioelectronics 240 (2023): 115635.

[129] X. Xue, Y. S. Kim, A. I. Ponce-Arias, et al., “A Patterned Human Neural Tube Model Using Microfluidic Gradients,” Nature 628, no. 8007 (2024): 391–399.

[130] A. Abdulla, H. Yan, S. Chen, et al., “A Multichannel Microfluidic Device for Revealing the Neurotoxic Effects of Bisphenol S on Cerebral Organoids Under Low-Dose Constant Exposure,” Biosensors & Bioelectronics 267 (2025): 116754.

[131] G. Saorin, I. Caligiuri, and F. Rizzolio, “Microfluidic Organoids-On-a-Chip: The Future of Human Models,” Seminars in Cell & Developmental Biology 144 (2023): 41–54.

[132] P. Sokolowska, A. Zuchowska, and Z. Brzozka, “Why Can Organoids Improve Current Organ-On-Chip Platforms?,” Organoids 1, no. 1 (2022): 69–84.

[133] E. Berger, C. Magliaro, N. Paczia, et al., “Millifluidic Culture Improves Human Midbrain Organoid Vitality and Differentiation,” Lab on a Chip 18, no. 20 (2018): 3172–3183.

[134] G. D. Vatine, R. Barrile, M. J. Workman, et al., “Human iPSC-Derived Blood-Brain Barrier Chips Enable Disease Modeling and Personalized Medicine Applications,” Cell Stem Cell 24, no. 6 (2019): 995–1005.e6.

[135] F. Alghannam, M. Alayed, S. Alfihed, et al., “Recent Progress in PDMS-Based Microfluidics Toward Integrated Organ-on-a-Chip Biosensors and Personalized Medicine,” Biosensors-Basel 15, no. 2 (2025): 76.

[136] S. Zhang, Z. Wan, and R. D. Kamm, “Vascularized Organoids on a Chip: Strategies for Engineering Organoids With Functional Vasculature,” Lab on a Chip 21, no. 3 (2021): 473–488.

[137] Y. J. Shin, D. Safina, Y. Zheng, and S. Levenberg, “Microvascularization in 3D Human Engineered Tissue and Organoids,” Annual Review of Biomedical Engineering 27, no. 1 (2025): 473–498.

[138] M. A. Lancaster, “Brain Organoids Get Vascularized,” Nature Biotechnology 36, no. 5 (2018): 407–408.

[139] E. E. Crouch, A. Bhaduri, M. G. Andrews, et al., “Ensembles of Endothelial and Mural Cells Promote Angiogenesis in Prenatal Human Brain,” Cell 185, no. 20 (2022): 3753–3769.e18.

[140] X. Zhao, Z. Xu, L. Xiao, et al., “Review on the Vascularization of Organoids and Organoids-on-a-Chip,” Frontiers in Bioengineering and Biotechnology 9 (2021): 637048.

[141] M. Shaji, A. Tamada, K. Fujimoto, K. Muguruma, S. L. Karsten, and R. Yokokawa, “Deciphering Potential Vascularization Factors of On-Chip Co-Cultured hiPSC-Derived Cerebral Organoids,” Lab on a Chip 24, no. 4 (2024): 680–696.

[142] L. Dao, Z. You, L. Lu, et al., “Modeling Blood-Brain Barrier Formation and Cerebral Cavernous Malformations in Human PSC-Derived Organoids,” Cell Stem Cell 31, no. 6 (2024): 818–833.e11.

[143] Y. Ahn, J. H. An, H. J. Yang, et al., “Human Blood Vessel Organoids Penetrate Human Cerebral Organoids and Form a Vessel-Like System,” Cells 10, no. 8 (2021): 2036.

[144] I. Salmon, S. Grebenyuk, A. R. Abdel Fattah, et al., “Engineering Neurovascular Organoids With 3D Printed Microfluidic Chips,” Lab on a Chip 22, no. 8 (2022): 1615–1629.

[145] L. Kistemaker, E. J. van Bodegraven, H. E. de Vries, and E. M. Hol, “Vascularized Human Brain Organoids: Current Possibilities and Prospects,” Trends in Biotechnology 43, no. 6 (2025): 1275–1285.

[146] C. D'Antoni, L. Mautone, C. Sanchini, et al., “Unlocking Neural Function With 3D In Vitro Models: A Technical Review of Self-Assembled, Guided, and Bioprinted Brain Organoids and Their Applications in the Study of Neurodevelopmental and Neurodegenerative Disorders,” International Journal of Molecular Sciences 24, no. 13 (2023): 10762.

[147] Q. Gu, E. Tomaskovic-Crook, R. Lozano, et al., “Functional 3D Neural Mini-Tissues From Printed Gel-Based Bioink and Human Neural Stem Cells,” Advanced Healthcare Materials 5, no. 12 (2016): 1429–1438.

[148] R. M. Ferraro, P. S. Ginestra, M. Seiti, et al., “Three-Dimensional-Bioprinted Embedded-Based Cerebral Organoids: An Alternative Approach for Mini-Brain In Vitro Modeling Beyond Conventional Generation Methods,” Gels 11, no. 4 (2025): 284.

[149] A. Orr, F. Kalantarnia, S. Nazir, et al., “Recent Advances in 3D Bioprinted Neural Models: A Systematic Review on the Applications to Drug Discovery,” Advanced Drug Delivery Reviews 218 (2025): 115524.

[150] L. Xu, H. Ding, S. Wu, et al., “Artificial Meshed Vessel-Induced Dimensional Breaking Growth of Human Brain Organoids and Multiregional Assembloids,” ACS Nano 18, no. 38 (2024): 26201–26214.

[151] B. Rezaei, J. Giacomoni, F. Nilsson, et al., “Modular 3D Printed Platform for Fluidically Connected Human Brain Organoid Culture,” Biofabrication 16, no. 1 (2023): 015014.

[152] D. Joung, V. Truong, C. C. Neitzke, et al., “3D Printed Stem-Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds,” Advanced Functional Materials 28, no. 39 (2018): 1801850.

[153] J. Koffler, W. Zhu, X. Qu, et al., “Biomimetic 3D-Printed Scaffolds for Spinal Cord Injury Repair,” Nature Medicine 25, no. 2 (2019): 263–269.

[154] G. Ricci, F. Gibelli, and A. Sirignano, “Three-Dimensional Bioprinting of Human Organs and Tissues: Bioethical and Medico-Legal Implications Examined Through a Scoping Review,” Bioengineering 10, no. 9 (2023): 1052.

[155] Y. Qiang, P. Artoni, K. J. Seo, et al., “Transparent Arrays of Bilayer-Nanomesh Microelectrodes for Simultaneous Electrophysiology and Two-Photon Imaging in the Brain,” Science Advances 4, no. 9 (2018): eaat0626.

[156] O. Revah, F. Gore, K. W. Kelley, et al., “Maturation and Circuit Integration of Transplanted Human Cortical Organoids,” Nature 610, no. 7931 (2022): 319–326.

[157] T. Sharf, T. van der Molen, S. M. K. Glasauer, et al., “Functional Neuronal Circuitry and Oscillatory Dynamics in Human Brain Organoids,” Nature Communications 13, no. 1 (2022): 4403.

[158] Q. Huang, B. Tang, J. C. Romero, et al., “Shell Microelectrode Arrays (MEAs) for Brain Organoids,” Science Advances 8, no. 33 (2022): eabq5031.

[159] P. Le Floch, Q. Li, Z. Lin, et al., “Stretchable Mesh Nanoelectronics for 3D Single-Cell Chronic Electrophysiology From Developing Brain Organoids,” Advanced Materials 34, no. 11 (2022): e2106829.

[160] D. Linaro, B. Vermaercke, R. Iwata, et al., “Xenotransplanted Human Cortical Neurons Reveal Species-Specific Development and Functional Integration Into Mouse Visual Circuits,” Neuron 104, no. 5 (2019): 972–986.e6.

[161] K. Tasnim and J. Liu, “Emerging Bioelectronics for Brain Organoid Electrophysiology,” Journal of Molecular Biology 434, no. 3 (2022): 167165.

[162] M. O'Hara-Wright, S. Mobini, and A. Gonzalez-Cordero, “Bioelectric Potential in Next-Generation Organoids: Electrical Stimulation to Enhance 3D Structures of the Central Nervous System,” Frontiers in Cell and Development Biology 10 (2022): 901652.

[163] X. H. Li, N. Hu, Z. H. Chang, et al., “Brain Organoid Maturation and Implantation Integration Based on Electrical Signals Input,” Journal of Advanced Research 73 (2025): 375–395.

[164] Q. Wang, X. Dong, D. Jiang, et al., “Bioelectronic Interfaces and Sensors for Neural Organoids,” Microsystems & Nanoengineering 11, no. 1 (2025): 172.

[165] J. T. Kim, T. Y. Kim, D. H. Youn, et al., “Human Embryonic Stem Cell-Derived Cerebral Organoids for Treatment of Mild Traumatic Brain Injury in a Mouse Model,” Biochemical and Biophysical Research Communications 635 (2022): 169–178.

[166] C. L. Fu, B. C. Dong, X. Jiang, D. Li, and J. Yao, “A Cell Therapy Approach Based on iPSC-Derived Midbrain Organoids for the Restoration of Motor Function in a Parkinson's Disease Mouse Model,” Heliyon 10, no. 2 (2024): e24234.

[167] M. Kano, H. Sasaki, T. Miwata, and H. Suga, “Recipe for Pituitary Organoids,” Frontiers in Endocrinology 13 (2022): 1025825.

[168] S. Taga, H. Suga, T. Nakano, et al., “Generation and Purification of ACTH-Secreting hPSC-Derived Pituitary Cells for Effective Transplantation,” Stem Cell Reports 18, no. 8 (2023): 1657–1671.

[169] Y. Li, Y. Gu, Z. Wang, et al., “GelMA Hydrogel Encapsulating iPSC-Derived Human Spinal Cord Organoids Enhances Neural Regeneration and Restores Motor Function in Rat Spinal Cord Injury,” Journal of Biomedical Materials Research Part A 113, no. 10 (2025): e38001.

[170] B. B. Thomas, B. Lin, J. C. Martinez-Camarillo, et al., “Co-Grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons Rats,” Frontiers in Neuroscience 15 (2021): 752958.

[171] Z. Wang, S. N. Wang, T. Y. Xu, et al., “Cerebral Organoids Transplantation Improves Neurological Motor Function in Rat Brain Injury,” CNS Neuroscience & Therapeutics 26, no. 7 (2020): 682–697.

[172] Z. Bao, K. Fang, Z. Miao, et al., “Human Cerebral Organoid Implantation Alleviated the Neurological Deficits of Traumatic Brain Injury in Mice,” Oxidative Medicine and Cellular Longevity 2021 (2021): 6338722.

[173] K. Yamagami, B. Samata, D. Doi, et al., “Progranulin Enhances the Engraftment of Transplanted Human iPS Cell-Derived Cerebral Neurons,” Stem Cells Translational Medicine 13, no. 11 (2024): 1113–1128.

[174] S. B. Xu, X. R. Li, P. Fan, et al., “Single-Cell Transcriptome Landscape and Cell Fate Decoding in Human Brain Organoids After Transplantation,” Advanced Science 11, no. 28 (2024): e2402287.

[175] S. N. Wang, Z. Wang, T. Y. Xu, M. H. Cheng, W. L. Li, and C. Y. Miao, “Cerebral Organoids Repair Ischemic Stroke Brain Injury,” Translational Stroke Research 11, no. 5 (2020): 983–1000.

[176] S. Y. Cao, D. Yang, Z. Q. Huang, et al., “Cerebral Organoids Transplantation Repairs Infarcted Cortex and Restores Impaired Function After Stroke,” NPJ Regenerative Medicine 8, no. 1 (2023): 27.

[177] T. Kitahara, H. Sakaguchi, A. Morizane, T. Kikuchi, S. Miyamoto, and J. Takahashi, “Axonal Extensions Along Corticospinal Tracts From Transplanted Human Cerebral Organoids,” Stem Cell Reports 15, no. 2 (2020): 467–481.

[178] S. W. Kim, H. J. Woo, E. H. Kim, et al., “Neural Stem Cells Derived From Human Midbrain Organoids as a Stable Source for Treating Parkinson's Disease: Midbrain Organoid-NSCs (Og-NSC) as a Stable Source for PD Treatment,” Progress in Neurobiology 204 (2021): 102086.

[179] X. Zheng, D. Han, W. Liu, et al., “Human iPSC-Derived Midbrain Organoids Functionally Integrate Into Striatum Circuits and Restore Motor Function in a Mouse Model of Parkinson's Disease,” Theranostics 13, no. 8 (2023): 2673–2692.

[180] X. Zheng, J. Chen, Z. Huang, Y. Zhang, and L. Zhou, “Efficacy and Safety Assessment of Homotopical Transplantation of iPSCs-Derived Midbrain Organoids Into the Substantia Nigra of Parkinsonian Rats,” Bioengineering & Translational Medicine 10, no. 5 (2025): e70014.

[181] Z. Wang, H. Zhao, X. Tang, et al., “CNS Organoid Surpasses Cell-Laden Microgel Assembly to Promote Spinal Cord Injury Repair,” Research 2022 (2022): 9832128.

[182] L. Ma, Z. Zhang, Y. Mu, et al., “Generation of Engineered Human Spinal Cord Organoid in Channel-Patterned Collagen and Transplantation for Spinal Cord Regeneration,” Biomaterials 327 (2025): 123753.

[183] Y. Zhu, R. Huang, L. Yu, et al., “Engineered Thoracic Spinal Cord Organoids for Transplantation After Spinal Cord Injury,” Nature Biomedical Engineering (2025).

[184] B. Lin, B. T. McLelland, R. B. Aramant, et al., “Retina Organoid Transplants Develop Photoreceptors and Improve Visual Function in RCS Rats With RPE Dysfunction,” Investigative Ophthalmology & Visual Science 61, no. 11 (2020): 34.

[185] N. Zhao, C. J. Zhang, X. Zhang, W. Wang, K. Jin, and Z. B. Jin, “Transplantation of Derivative Retinal Organoids From Chemically Induced Pluripotent Stem Cells Restored Visual Function,” NPJ Regenerative Medicine 9, no. 1 (2024): 42.

[186] Y. Iwama, Y. Sugase-Miyamoto, K. Onoue, et al., “Transplantation of Human Pluripotent Stem Cell-Derived Retinal Sheet in a Primate Model of Macular Hole,” Stem Cell Reports 19, no. 11 (2024): 1524–1533.

[187] B. T. McLelland, B. Lin, A. Mathur, et al., “Transplanted hESC-Derived Retina Organoid Sheets Differentiate, Integrate, and Improve Visual Function in Retinal Degenerate Rats,” Investigative Ophthalmology & Visual Science 59, no. 6 (2018): 2586–2603.

[188] K. Watari, S. Yamasaki, H. Y. Tu, et al., “Self-Organization, Quality Control, and Preclinical Studies of Human iPSC-Derived Retinal Sheets for Tissue-Transplantation Therapy,” Communications Biology 6, no. 1 (2023): 164.

[189] H. Y. Tu, T. Watanabe, H. Shirai, et al., “Medium- To Long-Term Survival and Functional Examination of Human iPSC-Derived Retinas in Rat and Primate Models of Retinal Degeneration,” eBioMedicine 39 (2019): 562–574.

[190] Q. Lei, R. Zhang, F. Yuan, and M. Xiang, “Integration and Differentiation of Transplanted Human iPSC-Derived Retinal Ganglion Cell Precursors in Murine Retinas,” International Journal of Molecular Sciences 25, no. 23 (2024): 12947.

[191] M. Mandai, M. Fujii, T. Hashiguchi, et al., “iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice,” Stem Cell Reports 8, no. 1 (2017): 69–83.

[192] Y. Hirami, M. Mandai, S. Sugita, et al., “Safety and Stable Survival of Stem-Cell-Derived Retinal Organoid for 2 Years in Patients With Retinitis Pigmentosa,” Cell Stem Cell 30, no. 12 (2023): 1585–1596.e6.

[193] D. S. Rajendran Nair, M. J. Seiler, J. C. Martinez-Camarillo, et al., “Stem Cell-Derived Co-Grafts Contribute to Retinal Reconstruction and Visual Functional Improvement in a Laser Damaged Rat Model,” Military Medical Research 12, no. 1 (2025): 23.

[194] N. Daviaud, R. H. Friedel, and H. Zou, “Vascularization and Engraftment of Transplanted Human Cerebral Organoids in Mouse Cortex,” eNeuro 5, no. 6 (2018): ENEURO.0219.

[195] A. A. Mansour, J. T. Gonçalves, C. W. Bloyd, et al., “An In Vivo Model of Functional and Vascularized Human Brain Organoids,” Nature Biotechnology 36, no. 5 (2018): 432–441.

[196] N. Altinisik, D. Rathinam, M. Tran, and J. Gopalakrishnan, “Brain Organoids Restore Cortical Damage,” Cell Stem Cell 30, no. 3 (2023): 241–242.

[197] X. Dong, S. B. Xu, X. Chen, et al., “Human Cerebral Organoids Establish Subcortical Projections in the Mouse Brain After Transplantation,” Molecular Psychiatry 26, no. 7 (2021): 2964–2976.

[198] M. N. Wilson, M. Thunemann, X. Liu, et al., “Multimodal Monitoring of Human Cortical Organoids Implanted in Mice Reveal Functional Connection With Visual Cortex,” Nature Communications 13, no. 1 (2022): 7945.

[199] M. Wang, L. Zhang, S. W. Novak, et al., “Morphological Diversification and Functional Maturation of Human Astrocytes in Glia-Enriched Cortical Organoid Transplanted in Mouse Brain,” Nature Biotechnology 43, no. 1 (2025): 52–62.

[200] K. W. Kelley, O. Revah, F. Gore, et al., “Host Circuit Engagement of Human Cortical Organoids Transplanted in Rodents,” Nature Protocols 19, no. 12 (2024): 3542–3567.

[201] G. Teasdale, A. Maas, F. Lecky, G. Manley, N. Stocchetti, and G. Murray, “The Glasgow Coma Scale at 40 Years: Standing the Test of Time,” Lancet Neurology 13, no. 8 (2014): 844–854.

[202] B. D. Greenwald, K. A. Harris, H. Ayyala, and D. J. Gordon, “Community Reintegration After Traumatic Brain Injury,” Physical Medicine and Rehabilitation Clinics of North America 35, no. 3 (2024): 637–650.

[203] N. S. Graham and D. J. Sharp, “Dementia After Traumatic Brain Injury,” BMJ 383 (2023): 2065.

[204] A. Khellaf, D. Z. Khan, and A. Helmy, “Recent Advances in Traumatic Brain Injury,” Journal of Neurology 266, no. 11 (2019): 2878–2889.

[205] The Lancet Neurology, “The Future Research Path of Traumatic Brain Injury,” Lancet Neurology 21, no. 4 (2022): 295.

[206] S. Péron, M. Droguerre, F. Debarbieux, et al., “A Delay Between Motor Cortex Lesions and Neuronal Transplantation Enhances Graft Integration and Improves Repair and Recovery,” Journal of Neuroscience 37, no. 7 (2017): 1820–1834.

[207] Z. He, C. H. P. Ong, J. Halper, and A. Bateman, “Progranulin Is a Mediator of the Wound Response,” Nature Medicine 9, no. 2 (2003): 225–229.

[208] M. Kanazawa, K. Kawamura, T. Takahashi, et al., “Multiple Therapeutic Effects of Progranulin on Experimental Acute Ischaemic Stroke,” Brain 138, no. 7 (2015): 1932–1948.

[209] V. L. Feigin, M. Brainin, B. Norrving, et al., “World Stroke Organization: Global Stroke Fact Sheet 2025,” International Journal of Stroke 20, no. 2 (2025): 132–144.

[210] V. L. Feigin and M. O. Owolabi, “Pragmatic Solutions to Reduce the Global Burden of Stroke: A World Stroke Organization-Lancet Neurology Commission,” Lancet Neurology 22, no. 12 (2023): 1160–1206.

[211] J. L. Saver, G. C. Fonarow, E. E. Smith, et al., “Time to Treatment With Intravenous Tissue Plasminogen Activator and Outcome From Acute Ischemic Stroke,” Journal of the American Medical Association 309, no. 23 (2013): 2480–2488.

[212] N. A. Hilkens, B. Casolla, T. W. Leung, and F. E. de Leeuw, “Stroke,” Lancet 403, no. 10446 (2024): 2820–2836.

[213] T. G. Jovin, R. G. Nogueira, M. G. Lansberg, et al., “Thrombectomy for Anterior Circulation Stroke Beyond 6 h From Time Last Known Well (AURORA): A Systematic Review and Individual Patient Data Meta-Analysis,” Lancet 399, no. 10321 (2022): 249–258.

[214] H. Fan, H. Wang, Z. Lian, et al., “Dynamic Interactions Between Hemispheres Reveal a Compensatory Pathway for Motor Recovery in Moderate-To-Severe Subcortical Stroke,” Journal of Stroke 28, no. 1 (2026): 97–114.

[215] K. Yuan, X. Wang, C. Chen, C. C. Lau, W. C. Chu, and R. K. Tong, “Interhemispheric Functional Reorganization and Its Structural Base After BCI-Guided Upper-Limb Training in Chronic Stroke,” IEEE Transactions on Neural Systems and Rehabilitation Engineering 28, no. 11 (2020): 2525–2536.

[216] G. Yu, X. Wu, Z. Liu, et al., “Genetic Influence and Neural Pathways Underlying the Dose-Response Relationships Between Wearable-Measured Physical Activity and Mental Health in Adolescence,” Psychiatry Research 349 (2025): 116503.

[217] Y. Liu, S. Peng, X. Wu, et al., “Neural, Cognitive and Psychopathological Signatures of a Prosocial or Delinquent Peer Environment During Early Adolescence,” Developmental Cognitive Neuroscience 73 (2025): 101566.

[218] S. P. Yu, J. K. Tung, Z. Z. Wei, et al., “Optochemogenetic Stimulation of Transplanted iPS-NPCs Enhances Neuronal Repair and Functional Recovery After Ischemic Stroke,” Journal of Neuroscience 39, no. 33 (2019): 6571–6594.

[219] G. Song, M. Zhao, H. Chen, et al., “The Application of Brain Organoid Technology in Stroke Research: Challenges and Prospects,” Frontiers in Cellular Neuroscience 15 (2021): 646921.

[220] K. Takahashi, K. Tanabe, M. Ohnuki, et al., “Induction of Pluripotent Stem Cells From Adult Human Fibroblasts by Defined Factors,” Cell 131, no. 5 (2007): 861–872.

[221] Y. X. Hao, C. R. Li, Z. J. Lu, et al., “Remodeling and Repair of the Damaged Brain: The Potential and Challenges of Organoids for Ischaemic Stroke,” Journal of Translational Medicine 23, no. 1 (2025): 767.

[222] D. K. Cullen, W. J. Gordián-Vélez, L. A. Struzyna, et al., “Bundled Three-Dimensional Human Axon Tracts Derived From Brain Organoids,” iScience 21 (2019): 57–67.

[223] C. J. Sommer, “Ischemic Stroke: Experimental Models and Reality,” Acta Neuropathologica 133, no. 2 (2017): 245–261.

[224] S. Y. Cao, M. D. Tao, S. N. Lou, et al., “Functional Reconstruction of the Impaired Cortex and Motor Function by hMGEOs Transplantation in Stroke,” Biochemical and Biophysical Research Communications 671 (2023): 87–95.

[225] F. Fu, Z. Qin, C. Xu, et al., “Magnetic Resonance Imaging-Three-Dimensional Printing Technology Fabricates Customized Scaffolds for Brain Tissue Engineering,” Neural Regeneration Research 12, no. 4 (2017): 614–622.

[226] H. Sun, C. Dong, Y. Li, et al., “Topographic and Temporal Patterns of Dyskinesia in Multiple System Atrophy With Predominant Parkinsonism,” Journal of Neurorestoratology 12, no. 4 (2024): 100145.

[227] Y. J. Yeap, T. J. W. Teddy, M. J. Lee, M. Goh, and K. L. Lim, “From 2D to 3D: Development of Monolayer Dopaminergic Neuronal and Midbrain Organoid Cultures for Parkinson's Disease Modeling and Regenerative Therapy,” International Journal of Molecular Sciences 24, no. 3 (2023): 2523.

[228] T. W. Kim, J. Piao, S. Y. Koo, et al., “Biphasic Activation of WNT Signaling Facilitates the Derivation of Midbrain Dopamine Neurons From hESCs for Translational Use,” Cell Stem Cell 28, no. 2 (2021): 343–355.e5.

[229] B. Ballion, M. L. Bonnet, S. Brot, and A. Gaillard, “Electrophysiological Characterisation of Intranigral-Grafted hiPSC-Derived Dopaminergic Neurons in a Mouse Model of Parkinson's Disease,” Stem Cell Research & Therapy 16, no. 1 (2025): 232.

[230] N. Sawamoto, D. Doi, E. Nakanishi, et al., “Phase I/II Trial of iPS-Cell-Derived Dopaminergic Cells for Parkinson's Disease,” Nature 641, no. 8064 (2025): 971–977.

[231] C. L. Fu, X. Jiang, B. C. Dong, D. Li, X. Y. She, and J. Yao, “Protocol for Transplantation of Cells Derived From Human Midbrain Organoids Into a Parkinson's Disease Mouse Model to Restore Motor Function,” STAR Protocols 5, no. 3 (2024): 103251.

[232] N. Prudon, L. Cordero-Espinoza, M. Abarkan, et al., “Bioreactor-Produced iPSCs-Derived Dopaminergic Neuron-Containing Neural Microtissues Innervate and Normalize Rotational Bias in a Dose-Dependent Manner in a Parkinson Rat Model,” Neurotherapeutics 21, no. 5 (2024): e00436.

[233] C. Li, Z. Wu, L. Zhou, et al., “Temporal and Spatial Cellular and Molecular Pathological Alterations With Single-Cell Resolution in the Adult Spinal Cord After Injury,” Signal Transduction and Targeted Therapy 7, no. 1 (2022): 65.

[234] D. D. Hodgkiss, S. J. T. Balthazaar, J. F. Welch, et al., “Short- and Long-Term Effects of Transcutaneous Spinal Cord Stimulation on Autonomic Cardiovascular Control and Arm-Crank Exercise Capacity in Individuals With a Spinal Cord Injury (STIMEX-SCI): Study Protocol,” BMJ Open 15, no. 1 (2025): e089756.

[235] C. M. de Freria, E. Van Niekerk, A. Blesch, and P. Lu, “Neural Stem Cells: Promoting Axonal Regeneration and Spinal Cord Connectivity,” Cells 10, no. 12 (2021): 3296.

[236] R. C. Assunção Silva, L. Pinto, and A. J. Salgado, “Cell Transplantation and Secretome Based Approaches in Spinal Cord Injury Regenerative Medicine,” Medicinal Research Reviews 42, no. 2 (2022): 850–896.

[237] J. Ribeiro, C. A. Procyk, E. L. West, et al., “Restoration of Visual Function in Advanced Disease After Transplantation of Purified Human Pluripotent Stem Cell-Derived Cone Photoreceptors,” Cell Reports 35, no. 3 (2021): 109022.

[238] H. Liu, Y. Ma, N. Gao, et al., “Identification and Characterization of Human Retinal Stem Cells Capable of Retinal Regeneration,” Science Translational Medicine 17, no. 791 (2025): eadp6864.

[239] Y. Xue, B. Lin, J. T. Chen, W. C. Tang, A. W. Browne, and M. J. Seiler, “The Prospects for Retinal Organoids in Treatment of Retinal Diseases,” Asia-Pacific Journal of Ophthalmology 11, no. 4 (2022): 314–327.

[240] R. Sims, B. Lin, Y. Xue, et al., “Effect of Immunosuppression on hESC-Derived Retina Organoids In Vitro and In Vivo,” Stem Cell Research & Therapy 16, no. 1 (2025): 165.

[241] T. Matsuyama, H. Y. Tu, J. Sun, et al., “Genetically Engineered Stem Cell-Derived Retinal Grafts for Improved Retinal Reconstruction After Transplantation,” iScience 24, no. 8 (2021): 102866.

[242] S. H. Chew, C. Martinez, K. R. Chirco, S. Kandoi, and D. A. Lamba, “Timed Notch Inhibition Drives Photoreceptor Fate Specification in Human Retinal Organoids,” Investigative Ophthalmology & Visual Science 63, no. 10 (2022): 12.

[243] M. Watanabe, T. Yamada, H. Y. Tu, et al., “Graft-Derived Horizontal Cells Contribute to Host-Graft Synapses in Degenerated Retinas After Retinal Organoid Transplantation,” Stem Cell Reports 20, no. 7 (2025): 102545.

[244] K. Kawai, M. T. Ho, Y. Ueno, et al., “Hyaluronan Improves Photoreceptor Differentiation and Maturation in Human Retinal Organoids,” Acta Biomaterialia 181 (2024): 117–132.

[245] E. E. Capowski, K. Samimi, S. J. Mayerl, et al., “Reproducibility and Staging of 3D Human Retinal Organoids Across Multiple Pluripotent Stem Cell Lines,” Development 146, no. 1 (2019): dev171686.

[246] J. D. Lai, J. E. Berlind, G. Fricklas, et al., “KCNJ2 Inhibition Mitigates Mechanical Injury in a Human Brain Organoid Model of Traumatic Brain Injury,” Cell Stem Cell 31, no. 4 (2024): 519–536.e8.

[247] D. Reumann, C. Krauditsch, M. Novatchkova, et al., “In Vitro Modeling of the Human Dopaminergic System Using Spatially Arranged Ventral Midbrain–Striatum–Cortex Assembloids,” Nature Methods 20, no. 12 (2023): 2034–2047.

[248] R. A. Wimmer, A. Leopoldi, M. Aichinger, et al., “Human Blood Vessel Organoids as a Model of Diabetic Vasculopathy,” Nature 565, no. 7740 (2019): 505–510.

[249] S. N. Wang, Z. Wang, X. Y. Wang, X. P. Zhang, T. Y. Xu, and C. Y. Miao, “Humanized Cerebral Organoids-Based Ischemic Stroke Model for Discovering of Potential Anti-Stroke Agents,” Acta Pharmacologica Sinica 44, no. 3 (2023): 513–523.

[250] R. Huang, Y. Zhu, H. Chen, et al., “Progress in Spinal Cord Organoid Research: Advancing Understanding of Neural Development, Disease Modelling, and Regenerative Medicine,” Biomaterials Translational 5, no. 4 (2024): 355–371.

[251] M. Watanabe, T. Yamada, C. Koike, M. Takahashi, M. Tachibana, and M. Mandai, “Transplantation of Genome-Edited Retinal Organoids Restores Some Fundamental Physiological Functions Coordinated With Severely Degenerated Host Retinas,” Stem Cell Reports 20, no. 2 (2025): 102393.

[252] M. B. Woodworth, L. C. Greig, and J. L. Goldberg, “Intrinsic and Induced Neuronal Regeneration in the Mammalian Retina,” Antioxidants & Redox Signaling 39, no. 16–18 (2023): 1039–1052.

[253] G. Zhou, R. Li, S. Sheng, et al., “Organoids and Organoid Extracellular Vesicles-Based Disease Treatment Strategies,” Journal of Nanobiotechnology 22, no. 1 (2024): 679.

[254] J. Zhou, M. Flores-Bellver, J. Pan, et al., “Human Retinal Organoids Release Extracellular Vesicles That Regulate Gene Expression in Target Human Retinal Progenitor Cells,” Scientific Reports 11, no. 1 (2021): 21128.

[255] P. Arthur, S. Kandoi, L. Sun, et al., “Biophysical, Molecular and Proteomic Profiling of Human Retinal Organoid-Derived Exosomes,” Pharmaceutical Research 40, no. 4 (2023): 801–816.

[256] P. Arthur, S. Kandoi, A. Kalvala, et al., “Cannabidiol-Loaded Retinal Organoid-Derived Extracellular Vesicles Protect Oxidatively Stressed ARPE-19 Cells,” Biomedicine 13, no. 5 (2025): 1167.

[257] S. Lee, J. Han, J. Yang, et al., “Exosomes From Human iPSC-Derived Retinal Organoids Enhance Corneal Epithelial Wound Healing,” International Journal of Molecular Sciences 25, no. 16 (2024): 8925.

[258] J. W. Han, H. S. Chang, J. Y. Yang, et al., “Intravitreal Administration of Retinal Organoids-Derived Exosomes Alleviates Photoreceptor Degeneration in Royal College of Surgeons Rats by Targeting the Mitogen-Activated Protein Kinase Pathway,” International Journal of Molecular Sciences 24, no. 15 (2023): 12068.

[259] X. Ji, S. Zhou, N. Wang, et al., “Cerebral-Organoid-Derived Exosomes Alleviate Oxidative Stress and Promote LMX1A-Dependent Dopaminergic Differentiation,” International Journal of Molecular Sciences 24, no. 13 (2023): 11048.

[260] I. Stankovic, P. Smit, J. Cross, et al., “Extracellular Vesicle Profiling Reveals Novel Autism Signatures in Patient-Derived Forebrain Organoids,” Translational Psychiatry 15, no. 1 (2025): 393.

[261] V. V. T. Nguyen, K. W. Witwer, M. C. Verhaar, D. Strunk, and B. W. M. van Balkom, “Functional Assays to Assess the Therapeutic Potential of Extracellular Vesicles,” Journal of Extracellular Vesicles 10, no. 1 (2020): e12033.

[262] Z. Szvicsek, Á. Oszvald, L. Szabó, et al., “Extracellular Vesicle Release From Intestinal Organoids Is Modulated by Apc Mutation and Other Colorectal Cancer Progression Factors,” Cellular and Molecular Life Sciences 76, no. 12 (2019): 2463–2476.

[263] A. Chansaenroj, C. Adine, S. Charoenlappanit, et al., “Magnetic Bioassembly Platforms Towards the Generation of Extracellular Vesicles From Human Salivary Gland Functional Organoids for Epithelial Repair,” Bioactive Materials 18 (2022): 151–163.

[264] A. Al Hrout, M. P. Levesque, and R. Chahwan, “Investigating the Tumor-Immune Microenvironment Through Extracellular Vesicles From Frozen Patient Biopsies and 3D Cultures,” Frontiers in Immunology 14 (2023): 1176175.

[265] A. Sasaki, M. Kuroha, M. Tosa, et al., “Evaluation of Organoid-Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross-Sectional Study,” Clinical and Translational Science 18, no. 6 (2025): e70270.

[266] C. Hering and A. K. Shetty, “Extracellular Vesicles Derived From Neural Stem Cells, Astrocytes, and Microglia as Therapeutics for Easing TBI-Induced Brain Dysfunction,” Stem Cells Translational Medicine 12, no. 3 (2023): 140–153.

[267] K. Xie, Y. Mo, E. Yue, N. Shi, and K. Liu, “Exosomes Derived From M2-Type Microglia Ameliorate Oxygen-Glucose Deprivation/Reoxygenation-Induced HT22 Cell Injury by Regulating miR-124-3p/NCOA4-Mediated Ferroptosis,” Heliyon 9, no. 7 (2023): e17592.

[268] G. Schwarz, X. Ren, W. Xie, H. Guo, Y. Jiang, and J. Zhang, “Engineered Exosomes: A Promising Drug Delivery Platform With Therapeutic Potential,” Frontiers in Molecular Biosciences 12 (2025): 1583992.

[269] Y. Y. Liu, Y. Li, L. Wang, et al., “Mesenchymal Stem Cell-Derived Exosomes Regulate Microglia Phenotypes: A Promising Treatment for Acute Central Nervous System Injury,” Neural Regeneration Research 18, no. 8 (2023): 1657–1665.

[270] X. Pei, Y. Li, L. Zhu, and Z. Zhou, “Astrocyte-Derived Exosomes Transfer miR-190b to Inhibit Oxygen and Glucose Deprivation-Induced Autophagy and Neuronal Apoptosis,” Cell Cycle 19, no. 8 (2020): 906–917.

[271] R. Upadhya, W. Zingg, S. Shetty, and A. K. Shetty, “Astrocyte-Derived Extracellular Vesicles: Neuroreparative Properties and Role in the Pathogenesis of Neurodegenerative Disorders,” Journal of Controlled Release 323 (2020): 225–239.

[272] P. Proia, G. Schiera, M. Mineo, et al., “Astrocytes Shed Extracellular Vesicles That Contain Fibroblast Growth Factor-2 and Vascular Endothelial Growth Factor,” International Journal of Molecular Medicine 21, no. 1 (2008): 63–67.

[273] A. D. Vogel, R. Upadhya, and A. K. Shetty, “Neural Stem Cell Derived Extracellular Vesicles: Attributes and Prospects for Treating Neurodegenerative Disorders,” eBioMedicine 38 (2018): 273–282.

[274] E. J. Lee, Y. Choi, H. J. Lee, D. W. Hwang, and D. S. Lee, “Human Neural Stem Cell-Derived Extracellular Vesicles Protect Against Parkinson's Disease Pathologies,” Journal of Nanobiotechnology 20, no. 1 (2022): 198.

[275] A. Hoshino, H. S. Kim, L. Bojmar, et al., “Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers,” Cell 182, no. 4 (2020): 1044–1061.e18.

[276] Y. Fu, Y. L. Zhang, R. Q. Liu, et al., “Exosome lncRNA IFNG-AS1 Derived From Mesenchymal Stem Cells of Human Adipose Ameliorates Neurogenesis and ASD-Like Behavior in BTBR Mice,” Journal of Nanobiotechnology 22, no. 1 (2024): 66.

[277] C. Vandendriessche, S. Balusu, C. Van Cauwenberghe, et al., “Importance of Extracellular Vesicle Secretion at the Blood-Cerebrospinal Fluid Interface in the Pathogenesis of Alzheimer's Disease,” Acta Neuropathologica Communications 9, no. 1 (2021): 143.

[278] M. Chen, C. Luo, J. Zhao, G. Devarajan, and H. Xu, “Immune Regulation in the Aging Retina,” Progress in Retinal and Eye Research 69 (2019): 159–172.

[279] R. Kubota, J. Gregory, S. Henry, and N. L. Mata, “Pharmacotherapy for Metabolic and Cellular Stress in Degenerative Retinal Diseases,” Drug Discovery Today 25, no. 2 (2020): 292–304.

[280] M. Flores-Bellver, J. Mighty, S. Aparicio-Domingo, et al., “Extracellular Vesicles Released by Human Retinal Pigment Epithelium Mediate Increased Polarised Secretion of Drusen Proteins in Response to AMD Stressors,” Journal of Extracellular Vesicles 10, no. 13 (2021): e12165.

[281] S. Huang, Y. Zeng, Q. Guo, T. Zou, and Z. Q. Yin, “Small Extracellular Vesicles of Organoid-Derived Human Retinal Stem Cells Remodel Müller Cell Fate via miRNA: A Novel Remedy for Retinal Degeneration,” Journal of Controlled Release 370 (2024): 405–420.

[282] Z. Zhu, Y. Cheng, X. Liu, et al., “Advances in the Development and Application of Human Organoids: Techniques, Applications, and Future Perspectives,” Cell Transplantation 34 (2025): 9636897241303271.

[283] H. E. Marei, “Stem Cell Therapy: A Revolutionary Cure or a Pandora's Box,” Stem Cell Research & Therapy 16, no. 1 (2025): 255.

[284] H. Kim, R. D. Kamm, G. Vunjak-Novakovic, and J. C. Wu, “Progress in Multicellular Human Cardiac Organoids for Clinical Applications,” Cell Stem Cell 29, no. 4 (2022): 503–514.

[285] X. Y. Tang, S. Wu, D. Wang, et al., “Human Organoids in Basic Research and Clinical Applications,” Signal Transduction and Targeted Therapy 7, no. 1 (2022): 168.

[286] R. Nishinakamura, “Advances and Challenges Toward Developing Kidney Organoids for Clinical Applications,” Cell Stem Cell 30, no. 8 (2023): 1017–1027.

[287] S. P. Pașca, P. Arlotta, P. Campbell, et al., “The Need for a Global Effort to Attend to Human Neural Organoid and Assembloid Research,” Science 390, no. 6773 (2025): 574–577.

[288] J. Li, S. M. Dang, S. Sengupta, et al., “Organoid Modeling Reveals the Tumorigenic Potential of the Alveolar Progenitor Cell State,” EMBO Journal 44, no. 6 (2025): 1804–1828.

[289] M. R. Sargen, E. K. Cahoon, K. J. Yu, et al., “Spectrum of Nonkeratinocyte Skin Cancer Risk Among Solid Organ Transplant Recipients in the US,” JAMA Dermatology 158, no. 4 (2022): 414–425.

[290] X. Yuan, J. Wu, Z. Sun, et al., “Preclinical Efficacy and Safety of Encapsulated Proliferating Human Hepatocyte Organoids in Treating Liver Failure,” Cell Stem Cell 31, no. 4 (2024): 484–498.e5.

[291] S. M. H. Rizvi, B. Aagnes, H. Holdaas, et al., “Long-Term Change in the Risk of Skin Cancer After Organ Transplantation: A Population-Based Nationwide Cohort Study,” JAMA Dermatology 153, no. 12 (2017): 1270–1277.

[292] P. N. Nwokoye and O. J. Abilez, “Bioengineering Methods for Vascularizing Organoids,” Cell Reports Methods 4, no. 6 (2024): 100779.

[293] E. LaMontagne, A. R. Muotri, and A. J. Engler, “Recent Advancements and Future Requirements in Vascularization of Cortical Organoids,” Frontiers in Bioengineering and Biotechnology 10 (2022): 1048731.

[294] A. Vargas-Valderrama, A. Messina, M. T. Mitjavila-Garcia, and H. Guenou, “The Endothelium, a Key Actor in Organ Development and hPSC-Derived Organoid Vascularization,” Journal of Biomedical Science 27, no. 1 (2020): 67.

[295] S. M. Boutom, T. P. Silva, S. P. Palecek, E. V. Shusta, T. G. Fernandes, and R. S. Ashton, “Central Nervous System Vascularization in Human Embryos and Neural Organoids,” Cell Reports 43, no. 12 (2024): 115068.

[296] X. Y. Sun, X. C. Ju, Y. Li, et al., “Generation of Vascularized Brain Organoids to Study Neurovascular Interactions,” eLife 11 (2022): e76707.

[297] S. Inagaki, S. Nakamura, Y. Kuse, et al., “Establishment of Vascularized Human Retinal Organoids From Induced Pluripotent Stem Cells,” Stem Cells 43, no. 3 (2025): sxae093.

[298] V. S. Shirure, C. C. W. Hughes, and S. C. George, “Engineering Vascularized Organoid-on-a-Chip Models,” Annual Review of Biomedical Engineering 23 (2021): 141–167.

[299] X. Chen, A. S. Aledia, C. M. Ghajar, et al., “Prevascularization of a Fibrin-Based Tissue Construct Accelerates the Formation of Functional Anastomosis With Host Vasculature,” Tissue Engineering, Part A 15, no. 6 (2009): 1363–1371.

[300] D. Li, X. Zhao, W. Kong, et al., “Engineered Subcutaneous Site for Optimal Organoid Transplantation,” Engineering 53, no. 10 (2025).

[301] A. Bond, V. Bruno, N. Sulaiman, J. Johnson, S. George, and R. Ascione, “In-Situ Vascular Regeneration by Host Cells of Acellular Human Saphenous Vein Implanted in Porcine Carotid Artery,” International Journal of Molecular Sciences 26, no. 10 (2025): 4718.

[302] X. Meng, Y. Xing, J. Li, et al., “Rebuilding the Vascular Network: In Vivo and In Vitro Approaches,” Frontiers in Cell and Development Biology 9 (2021): 639299.

[303] D. S. Masson-Meyers, F. Tabatabaei, L. Steinhaus, J. M. Toth, and L. Tayebi, “Development of Fibroblast/Endothelial Cell-Seeded Collagen Scaffolds for In Vitro Prevascularization,” Journal of Biomedical Materials Research. Part B, Applied Biomaterials 111, no. 3 (2023): 633–645.

[304] M. Kataoka, C. Gyngell, J. Savulescu, and T. Sawai, “The Ethics of Human Brain Organoid Transplantation in Animals,” Neuroethics 16, no. 3 (2023): 27.

[305] H. I. Chen, J. A. Wolf, R. Blue, et al., “Transplantation of Human Brain Organoids: Revisiting the Science and Ethics of Brain Chimeras,” Cell Stem Cell 25, no. 4 (2019): 462–472.

[306] X. Gao, Y. Wang, X. Chen, and S. Gao, “Interface, Interaction, and Intelligence in Generalized Brain-Computer Interfaces,” Trends in Cognitive Sciences 25, no. 8 (2021): 671–684.

[307] M. Alam, W. Rodrigues, B. N. Pham, and N. V. Thakor, “Brain-Machine Interface Facilitated Neurorehabilitation via Spinal Stimulation After Spinal Cord Injury: Recent Progress and Future Perspectives,” Brain Research 1646 (2016): 25–33.

[308] Y. P. Shen and Z. Kokaia, “Brain Organoid Transplantation: A Comprehensive Guide to the Latest Advances and Practical Applications-A Systematic Review,” Cells 14, no. 14 (2025): 1074.

[309] D. J. McFarland, “Brain-Computer Interfaces for Amyotrophic Lateral Sclerosis,” Muscle & Nerve 61, no. 6 (2020): 702–707.

[310] H. Lorach, A. Galvez, V. Spagnolo, et al., “Walking Naturally After Spinal Cord Injury Using a Brain-Spine Interface,” Nature 618, no. 7963 (2023): 126–133.

[311] G. Maisumu, S. Willerth, M. W. Nestor, et al., “Brain Organoids: Building Higher-Order Complexity and Neural Circuitry Models,” Trends in Biotechnology 43, no. 7 (2025): 1583–1598.

[312] J. V. Rosenfeld and Y. T. Wong, “Neurobionics and the Brain-Computer Interface: Current Applications and Future Horizons,” Medical Journal of Australia 206, no. 8 (2017): 363–368.

[313] L. He, Z. Sun, J. Li, et al., “Electrical Stimulation at Nanoscale Topography Boosts Neural Stem Cell Neurogenesis Through the Enhancement of Autophagy Signaling,” Biomaterials 268 (2021): 120585.

[314] M. Milosevic, T. Nakanishi, A. Sasaki, et al., “Cortical re-Organization After Traumatic Brain Injury Elicited Using Functional Electrical Stimulation Therapy: A Case Report,” Frontiers in Neuroscience 15 (2021): 693861.

[315] N. Hu, J. X. Shi, C. Chen, et al., “Constructing Organoid-Brain-Computer Interfaces for Neurofunctional Repair After Brain Injury,” Nature Communications 15, no. 1 (2024): 9580.

[316] W. U. Khan, Z. Shen, S. M. Mugo, H. Wang, and Q. Zhang, “Implantable Hydrogels as Pioneering Materials for Next-Generation Brain-Computer Interfaces,” Chemical Society Reviews 54, no. 6 (2025): 2832–2880.

[317] N. Driscoll, R. E. Rosch, B. B. Murphy, et al., “Multimodal In Vivo Recording Using Transparent Graphene Microelectrodes Illuminates Spatiotemporal Seizure Dynamics at the Microscale,” Communications Biology 4, no. 1 (2021): 136.

[318] D. Hernández, L. A. Rooney, M. Daniszewski, et al., “Culture Variabilities of Human iPSC-Derived Cerebral Organoids Are a Major Issue for the Modelling of Phenotypes Observed in Alzheimer's Disease,” Stem Cell Reviews and Reports 18, no. 2 (2022): 718–731.

[319] K. R. Chirco, S. Chew, A. T. Moore, J. L. Duncan, and D. A. Lamba, “Allele-Specific Gene Editing to Rescue Dominant CRX-Associated LCA7 Phenotypes in a Retinal Organoid Model,” Stem Cell Reports 16, no. 11 (2021): 2690–2702.

[320] C. L. Gardner, M. Pavel-Dinu, K. Dobbs, et al., “Gene Editing Rescues In Vitro T Cell Development of RAG2-Deficient Induced Pluripotent Stem Cells in an Artificial Thymic Organoid System,” Journal of Clinical Immunology 41, no. 5 (2021): 852–862.

[321] A. Nash, N. Lokhorst, and O. Veiseh, “Localized Immunomodulation Technologies to Enable Cellular and Organoid Transplantation,” Trends in Molecular Medicine 29, no. 8 (2023): 635–645.

[322] A. Loupy, E. Preka, X. Chen, H. Wang, J. He, and K. Zhang, “Reshaping Transplantation With AI, Emerging Technologies and Xenotransplantation,” Nature Medicine 31, no. 7 (2025): 2161–2173.

[323] S. Arjmandmazidi, H. R. Heidari, T. Ghasemnejad, et al., “An In-Depth Overview of Artificial Intelligence (AI) Tool Utilization Across Diverse Phases of Organ Transplantation,” Journal of Translational Medicine 23, no. 1 (2025): 678.

[324] C. He, N. C. Kalafut, S. O. Sandoval, et al., “BOMA, a Machine-Learning Framework for Comparative Gene Expression Analysis Across Brains and Organoids,” Cell Reports Methods 3, no. 2 (2023): 100409.

[325] S. Maramraju, A. Kowalczewski, A. Kaza, et al., “AI-Organoid Integrated Systems for Biomedical Studies and Applications,” Bioengineering & Translational Medicine 9, no. 2 (2024): e10641.

[326] T. Asano, H. Suga, H. Niioka, et al., “A Deep Learning Approach to Predict Differentiation Outcomes in Hypothalamic-Pituitary Organoids,” Communications Biology 7, no. 1 (2024): 1468.

[327] E. Kegeles, A. Naumov, E. A. Karpulevich, P. Volchkov, and P. Baranov, “Convolutional Neural Networks Can Predict Retinal Differentiation in Retinal Organoids,” Frontiers in Cellular Neuroscience 14 (2020): 171.

[328] J. Badai, Q. Bu, and L. Zhang, “Review of Artificial Intelligence Applications and Algorithms for Brain Organoid Research,” Interdisciplinary Sciences 12, no. 4 (2020): 383–394.

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2026 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.