An immunological perspective is provided on how the breadth of rejection mechanisms that have been uncovered through decades of research and the relative simplicity of designing PSC immune evasion strategies to circumvent these mechanisms apply to the treatment of type 1 diabetes are discussed.
Abstract
Abstract Pluripotent stem cell (PSC)-based therapies hold the potential to unlock cures for numerous diseases, including, but not limited to, Parkinson’s disease, macular degeneration, heart failure, type 1 diabetes, and cancer. Yet as protocols to differentiate PSCs into therapeutically useful cell types have progressed rapidly, immunological rejection remains a major barrier that may limit the widespread use of such PSC-based therapies. In recent years, strategies to genetically modify PSCs to prevent immunological rejection of the downstream cell product have become a point of emphasis. Here, we provide an immunological perspective on these strategies, discussing the breadth of rejection mechanisms that have been uncovered through decades of research and the relative simplicity of designing PSC immune evasion strategies to circumvent these mechanisms. We focus in particular on how these strategies apply to the treatment of type 1 diabetes.
This review traces key field milestones and analyzes prospects and hurdles for next-generation iPSC therapies as autologous and allogeneic iPSC therapies complement each other for distinct clinical demands.
Anmin Wang, Yunpei Zhang, Hongkui Deng et al.· Cell Reports Medicine· 0 citations
Cerebrovascular and neurodegenerative diseases rank among the leading causes of death worldwide and represent an increasing socioeconomic burden, particularly in aging populations. Pluripotent stem cell (PSC)-based therapies have emerged as promising strategies for replacing lost neurons and restoring neural circuits in disorders of the central nervous system (CNS). However, major barriers remain, including poor survival, limited integration, and variable functional maturation of transplanted cells. These challenges currently limit the reproducibility and clinical translation of PSC-based therapies. Here, we examine these barriers with a particular focus on ischemic stroke and Parkinson's disease, two conditions that represent complementary models of acute and chronic neuronal loss and are among the most advanced indications for PSC-based transplantation. We discuss how programmed cell death signaling contributes not only to neuronal loss in these disorders but also to the limited survival of transplanted PSC-derived grafts. Building on this mechanistic framework, we highlight strategies that may improve graft survival and functional integration. Specifically, we propose an integrated approach that combines modulation of programmed cell death pathways, targeted activation of RAS signaling, optimization of mitochondrial health, and use of biocompatible scaffolds to support neuronal maturation and network integration. Together, these strategies provide a conceptual framework for improving the reliability and therapeutic efficacy of PSC-based cell transplantation therapies and accelerating their translation toward clinical application.Overview of strategies to enhance PSC-derived neural graft survival and integration through modulation of cell death pathways, RAS signaling, mitochondrial function, and extracellular scaffolds. Created in BioRender. Raudzus, F. (2026) https://BioRender.com/blr0ycj.
O. Chen, Kelvin K Hui, Fabian Raudzus et al.· Cell Death and Disease· 0 citations
This paper will provide the current information on stem cells used in the treatment of children and the many different types of stem cells, including: hematopoietic stem cells (and their derivatives), mesenchymal stem cells (and their derivatives), induced pluripotent stem cells, embryonic stem cells, tissue-specific progenitor cells, extracellular vesicles, and bioengineered products.
Hany E. Marei· Stem cell research & therape...· 0 citations
The article traces the trend of directed differentiation technologies evolving from two-dimensional culture to three-dimensional organoids and details their practical applications in diseases such as stroke, Alzheimer's disease, and spinal cord injury—particularly in spinal cord injury models, where transplanted cells have achieved long-distance axonal regeneration and circuit reconstruction.
Dai-Yi Yang· International Journal of Bio...· 0 citations
Key applications of iPSC technology in hemato-oncology are summarized, its major advantages and current limitations are discussed, and emerging directions are highlighted, including scalable iPSC-derived blood cell therapies for inherited and acquired bone marrow failure syndromes and leukemia.
Ivan Tesakov, M. Nasri, M. Klimiankou et al.· Frontiers in Immunology· 0 citations
A comprehensive literature review of preclinical models and clinical trials focusing on mesenchymal, hematopoietic, and pluripotent stem cells, evaluating their efficacy, safety, and manufacturing challenges found stem cell therapies demonstrate remarkable healing potential.
Somayeh Shamlou, Hossein Rostami, Ali Hassanzadeh et al.· Journal of Clinical and Tran...· 0 citations
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