Aging and rejuvenation of engineered cardiovascular tissues: from research to clinical application

Chang Liu , Jing Guo , Yanan Zhang , Meiyu Hu , Tian Hao , Dragos Cretoiu , Guoping Li , Junjie Xiao

The Journal of Cardiovascular Aging ›› 2024, Vol. 4 ›› Issue (4) : 21

PDF
The Journal of Cardiovascular Aging ›› 2024, Vol. 4 ›› Issue (4) :21 DOI: 10.20517/jca.2024.11
Review

Aging and rejuvenation of engineered cardiovascular tissues: from research to clinical application

Author information +
History +
PDF

Abstract

Aging is a key contributor to the pathogenesis of cardiovascular diseases (CVDs). However, current methods and models of CVD do not include the factor of aging due to the use of premature cardiomyocytes. There is an urgent need for an engineered cardiovascular tissue (ECT) model that includes aging as the greatest CVD risk factor to facilitate drug development for aged CVD patients. Cell therapy, which transplants pluripotent stem cell-derived cardiomyocytes in patients, was proved to be effective for cardiac repair, while the cell retention rate is limited. Alternatively, implantation of ECT could enable long-term retention of cells after translation and may result in rejuvenation in aged hearts. This review summarizes the key features of aging and the influencing factors in engineered cardiovascular tissues. The applications and challenges of engineered myocardium designed for clinical use are also discussed.

Keywords

Cardiovascular aging / engineered cardiovascular tissue / rejuvenation / clinical application

Cite this article

Download citation ▾
Chang Liu, Jing Guo, Yanan Zhang, Meiyu Hu, Tian Hao, Dragos Cretoiu, Guoping Li, Junjie Xiao. Aging and rejuvenation of engineered cardiovascular tissues: from research to clinical application. The Journal of Cardiovascular Aging, 2024, 4(4): 21 DOI:10.20517/jca.2024.11

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Ungvari Z,de Cabo R,Csiszar A.Mechanisms of vascular aging: new perspectives.J Gerontol A Biol Sci Med Sci2010;65:1028-41 PMCID:PMC2950814

[2]

Peiyong Z.Cardiomyocyte senescence and the potential therapeutic role of senolytics in the heart.J Cardiovasc Aging2024;4:18 PMCID:PMC11309366

[3]

López-Otín C,Partridge L,Kroemer G.Hallmarks of aging: An expanding universe.Cell2023;186:243-78

[4]

Bergmann O,Felker A.Dynamics of cell generation and turnover in the human heart.Cell2015;161:1566-75

[5]

Ozcebe SG.In need of age-appropriate cardiac models: impact of cell age on extracellular matrix therapy outcomes.Aging Cell2023;22:e13966 PMCID:PMC10652343

[6]

Feng J,Li Y.Versican promotes cardiomyocyte proliferation and cardiac repair.Circulation2024;149:1004-15

[7]

Budhathoki S,Sethu P.Engineered aging cardiac tissue chip model for studying cardiovascular disease.Cells Tissues Organs2022;211:348-59 PMCID:PMC8818062

[8]

Acun A,Zorlutuna P.In vitro aged, hiPSC-origin engineered heart tissue models with age-dependent functional deterioration to study myocardial infarction.Acta Biomater2019;94:372-91 PMCID:PMC6779061

[9]

Anderson R,Maggiorani D.Length-independent telomere damage drives post-mitotic cardiomyocyte senescence.EMBO J2019;38:e100492 PMCID:PMC6396144

[10]

Ye Y,Liu H.SIRT2 counteracts primate cardiac aging via deacetylation of STAT3 that silences CDKN2B.Nat Aging2023;3:1269-87

[11]

Mone P,Morciano G.Dysfunctional mitochondria elicit bioenergetic decline in the aged heart.J Cardiovasc Aging 42024;13 PMCID:PMC11250775

[12]

Abutaleb NO,Choi L.Lonafarnib and everolimus reduce pathology in iPSC-derived tissue engineered blood vessel model of Hutchinson-Gilford Progeria Syndrome.Sci Rep2023;13:5032 PMCID:PMC10050176

[13]

Atchison L,Cao K.A tissue engineered blood vessel model of hutchinson-gilford progeria syndrome using human iPSC-derived smooth muscle cells.Sci Rep2017;7:8168 PMCID:PMC5557922

[14]

Atchison L,Snyder-Mounts E.iPSC-derived endothelial cells affect vascular function in a tissue-engineered blood vessel model of hutchinson-gilford progeria syndrome.Stem Cell Reports2020;14:325-37 PMCID:PMC7013250

[15]

Miller JD,Kishinevsky S.Human iPSC-based modeling of late-onset disease via progerin-induced aging.Cell Stem Cell2013;13:691-705 PMCID:PMC4153390

[16]

Dechat T,Sengupta K.Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin.Genes Dev2008;22:832-53 PMCID:PMC2732390

[17]

Dogacan Y.From vitality to vulnerability: the impact of oxygen on cardiac function and regeneration.J Cardiovasc Aging2024;4:15 PMCID:PMC11062631

[18]

Ungvari Z,Kiss T.Endothelial dysfunction and angiogenesis impairment in the ageing vasculature.Nat Rev Cardiol2018;15:555-65 PMCID:PMC6612360

[19]

Salmon EE,Truskey GA.Application of oxidative stress to a tissue-engineered vascular aging model induces endothelial cell senescence and activation.Cells2020;9:1292 PMCID:PMC7290800

[20]

Spallarossa P,Aloi C.Doxorubicin induces senescence or apoptosis in rat neonatal cardiomyocytes by regulating the expression levels of the telomere binding factors 1 and 2.Am J Physiol Heart Circ Physiol2009;297:H2169-81

[21]

Maejima Y,Ito H,Isobe M.Induction of premature senescence in cardiomyocytes by doxorubicin as a novel mechanism of myocardial damage.Aging Cell2008;7:125-36

[22]

Liu C,Hu M.Metabolic targets in cardiac aging and rejuvenation.J Cardiovasc Aging2022;2:46

[23]

Bassat E.How can young extracellular matrix promote cardiac regeneration?.Circulation2024;149:1016-8

[24]

Tzahor E.A coalition to heal-the impact of the cardiac microenvironment.Science2022;377:eabm4443

[25]

Sun S,Tang X.Vascular endothelium-targeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model.Sci Adv2020;6:eaay5556 PMCID:PMC7030934

[26]

Zhuang L,Chen C.DYRK1B-STAT3 Drives cardiac hypertrophy and heart failure by impairing mitochondrial bioenergetics.Circulation2022;145:829-46

[27]

Bui L,Hall E.Engineering bioactive nanoparticles to rejuvenate vascular progenitor cells.Commun Biol2022;5:635 PMCID:PMC9243106

[28]

Zhang N,Ma Q.Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair.Stem Cell Res Ther2020;11:273 PMCID:PMC7346506

[29]

Grigorian-Shamagian L,Fereydooni S.Cardiac and systemic rejuvenation after cardiosphere-derived cell therapy in senescent rats.Eur Heart J2017;38:2957-67 PMCID:PMC5837602

[30]

Kang K,Xiao Y.Aged human cells rejuvenated by cytokine enhancement of biomaterials for surgical ventricular restoration.J Am Coll Cardiol2012;60:2237-49

[31]

Omori S,Johmura Y.Generation of a p16 reporter mouse and its use to characterize and target p16(high) cells in vivo.Cell Metab2020;32:814-28

[32]

Wang B,Gasek NS.An inducible p21-Cre mouse model to monitor and manipulate p21-highly-expressing senescent cells in vivo.Nat Aging2021;1:962-73 PMCID:PMC8746571

[33]

Amor C,Leibold J.Senolytic CAR T cells reverse senescence-associated pathologies.Nature2020;583:127-32 PMCID:PMC7583560

[34]

Suda M,Katsuumi G.Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice.Nat Aging2021;1:1117-26

[35]

Baker DJ,Tchkonia T.Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders.Nature2011;479:232-6 PMCID:PMC3468323

[36]

Farr JN,Doolittle ML.Local senolysis in aged mice only partially replicates the benefits of systemic senolysis.J Clin Invest2023;133:e162519 PMCID:PMC10104901

[37]

Demaria M,Youssef SA.An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA.Dev Cell2014;31:722-33 PMCID:PMC4349629

[38]

Ward MR,Connelly KA.Concise review: rational use of mesenchymal stem cells in the treatment of ischemic heart disease.Stem Cells Transl Med2018;7:543-50 PMCID:PMC6052612

[39]

Zhang K.Stem cell-derived exosome versus stem cell therapy.Nat Rev Bioeng2023;12:1-2 PMCID:PMC10092910

[40]

Zhang H,Pan T.Epicardial injection of allogeneic human-induced-pluripotent stem cell-derived cardiomyocytes in patients with advanced heart failure: protocol for a phase I/IIa dose-escalation clinical trial.BMJ Open2022;12:e056264 PMCID:PMC9083430

[41]

Gerbin KA,Murry CE.Enhanced electrical integration of engineered human myocardium via intramyocardial versus epicardial delivery in infarcted rat hearts.PLoS One2015;10:e0131446 PMCID:PMC4498815

[42]

Zhao X,Xiao D.Comparison of non-human primate versus human induced pluripotent stem cell-derived cardiomyocytes for treatment of myocardial infarction.Stem Cell Reports2018;10:422-35 PMCID:PMC5830958

[43]

Shiba Y,Zhu WZ.Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts.Nature2012;489:322-5 PMCID:PMC3443324

[44]

Romagnuolo R,Porta-Sánchez A.Human embryonic stem cell-derived cardiomyocytes regenerate the infarcted pig heart but induce ventricular tachyarrhythmias.Stem Cell Reports2019;12:967-81 PMCID:PMC6524945

[45]

Chong JJ,Don CW.Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.Nature2014;510:273-7 PMCID:PMC4154594

[46]

Liu YW,Yang X.Human embryonic stem cell-derived cardiomyocytes restore function in infarcted hearts of non-human primates.Nat Biotechnol2018;36:597-605 PMCID:PMC6329375

[47]

Nguyen PK,Rhee JW.Potential strategies to address the major clinical barriers facing stem cell regenerative therapy for cardiovascular disease: a review.JAMA Cardiol2016;1:953-62 PMCID:PMC5378463

[48]

Sekine H,Dobashi I.Cardiac cell sheet transplantation improves damaged heart function via superior cell survival in comparison with dissociated cell injection.Tissue Eng Part A2011;17:2973-80

[49]

Riegler J,Ebert A.Human engineered heart muscles engraft and survive long term in a rodent myocardial infarction model.Circ Res2015;117:720-30 PMCID:PMC4679370

[50]

Zimmermann WH,Wasmeier G.Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts.Nat Med2006;12:452-8

[51]

Weinberger F,Pecha S.Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells.Sci Transl Med2016;8:363ra148

[52]

Didié M,Rubart M.Parthenogenetic stem cells for tissue-engineered heart repair.J Clin Invest2013;123:1285-98 PMCID:PMC3582145

[53]

Rubart M,Nakajima H,Nakajima HO.Physiological coupling of donor and host cardiomyocytes after cellular transplantation.Circ Res2003;92:1217-24

[54]

Iseoka H,Fukushima S.Pivotal role of non-cardiomyocytes in electromechanical and therapeutic potential of induced pluripotent stem cell-derived engineered cardiac tissue.Tissue Eng Part A2018;24:287-300 PMCID:PMC5792250

[55]

Li J,Shiozaki M.Human pluripotent stem cell-derived cardiac tissue-like constructs for repairing the infarcted myocardium.Stem Cell Reports2017;9:1546-59 PMCID:PMC5829319

[56]

Jackman CP,Asfour H.Engineered cardiac tissue patch maintains structural and electrical properties after epicardial implantation.Biomaterials2018;159:48-58 PMCID:PMC5801076

[57]

Chachques JC,Lago N.Myocardial assistance by grafting a new bioartificial upgraded myocardium (MAGNUM clinical trial): one year follow-up.Cell Transplant2007;16:927-34

[58]

Menasché P,Hagège A.Transplantation of human embryonic stem cell-derived cardiovascular progenitors for severe ischemic left ventricular dysfunction.J Am Coll Cardiol2018;71:429-38

[59]

Cyranoski D.'Reprogrammed' stem cells approved to mend human hearts for the first time.Nature2018;557:619-20

[60]

Fioretta ES,Motta SE,Hoerstrup SP.Cardiovascular tissue engineering: from basic science to clinical application.Exp Gerontol2019;117:1-12

[61]

Kelm JM,Zürcher A.Functionality, growth and accelerated aging of tissue engineered living autologous vascular grafts.Biomaterials2012;33:8277-85

[62]

Zimmermann W.Tissue engineered heart repair from preclinical models to first-in-patient studies.Current Opinion in Physiology2020;14:70-7

[63]

Li Y,Bursac N.Age-dependent functional crosstalk between cardiac fibroblasts and cardiomyocytes in a 3D engineered cardiac tissue.Acta Biomater2017;55:120-30 PMCID:PMC5509073

[64]

Domae K,Yoshikawa Y.Clinical outcomes of autologous stem cell-patch implantation for patients with heart failure with nonischemic dilated cardiomyopathy.J Am Heart Assoc2021;10:e008649 PMCID:PMC8403293

[65]

Miyagawa S,Yoshikawa Y.Phase I clinical trial of autologous stem cell-sheet transplantation therapy for treating cardiomyopathy.J Am Heart Assoc2017;6:e003918 PMCID:PMC5532985

AI Summary AI Mindmap
PDF

153

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/