Cell-based immunotherapy, recognized as living drugs, is revolutionizing clinical treatment to advanced cancer and shaping the landscape of biomedical research for complex diseases. The differentiation of human pluripotent stem cells (PSCs) emerges as a novel platform with the potential to generate an unlimited supply of therapeutic immune cells, especially when coupled with gene modification techniques. PSC-based immunotherapy is expected to meet the vast clinical demand for living drugs. Here, we examine recent preclinical and clinical advances in PSC-based immunotherapy, focusing on PSC gene modification strategies and differentiation methods for producing therapeutic immune cells. We also discuss opportunities in this field and challenges in cell quality and safety and stresses the need for further research and transparency to unlock the full potential of PSC immunotherapies.
The ovary is a crucial gonadal organ that supports female reproductive and endocrine functions. Ovarian aging can result in decreased fertility and dysfunction across multiple organs. Research has demonstrated that cellular senescence in various cell types within the ovary can trigger a decline in ovarian function through distinct stress responses, resulting in ovarian aging. This review explores how cellular senescence may contribute to ovarian aging and reproductive failure. Additionally, we discuss the factors that cause ovarian cellular senescence, including the accumulation of advanced glycation end products, oxidative stress, mitochondrial dysfunction, DNA damage, telomere shortening, and exposure to chemotherapy. Furthermore, we discuss senescence in six distinct cell types, including oocytes, granulosa cells, ovarian theca cells, immune cells, ovarian surface epithelium, and ovarian endothelial cells, inside the ovary and explore their contribution to the accelerated ovarian aging. Lastly, we describe potential senotherapeutics for the treatment of ovarian aging and offer novel strategies for ovarian longevity.
Systemic lupus erythematosus (SLE) is characterized by the overproduction of autoantibodies, and B cells are considered to be the primary cells involved in the development of SLE. Studies have shown that DNA damage responses play a role in B cell activity in SLE. However, the exact role of DNA damage-induced transcript 3 (DDIT3) in humoral immune response and SLE pathogenesis remains unknown. We observed increased expression of DDIT3 in B cells of SLE patients and this expression was positively correlated with disease activity. In DDIT3-knockout mice, we observed disturbances in B cell development and differentiation, inhibition of B cell activation, and BCR signaling. In addition, DDIT3 deficiency leads to a reduction in T-cell-dependent humoral immune responses. Mechanistically, we found that DDIT3 promotes the transcription and expression of Itgad, which enhances PI3K signaling and B cell activation. Finally, we found that DDIT3 deficiency attenuated lupus autoimmunity and reduced germinal center responses. In conclusion, our study reveals for the first time the role of DDIT3 in adaptive immune responses, especially in B cell homeostasis, B cell activation, BCR signaling, and B cell function. These findings provide a new potential target for therapeutic intervention in SLE.
Hearing is one of the most vital sensory functions in human beings and a crucial means of perceiving and acquiring information from the natural environment. The advancement of human society is closely linked to the development of language, with hearing serving as the foundation for verbal communication. As individuals age, the deterioration of the auditory system becomes a significant factor contributing to sensory impairments in the elderly. In addition to hearing loss, the aging of the auditory system is also associated with cognitive decline and psychosocial disorders, which severely impact the quality of life for older adults. Currently, there are no effective treatments or interventions available for addressing the aging of the auditory system. Therefore, identifying biomarkers of the auditory system aging is of great significance. The Aging Biomarker Consortium of China has conducted a comprehensive evaluation of aging biomarkers in the auditory system, focusing on three dimensions: morphological, functional, and humoral biomarkers. This initiative aims to establish a foundation for assessing the degree of aging in the auditory system and to promote the management of auditory health in an aging society, ultimately enhancing the auditory health of the elderly population both in China and globally.