International Journal of Molecular and Cellular Medicine (IJMCM)

Induced pluripotent stem cells (iPSCs) represent a transformative approach in regenerative medicine, enabling personalized cell-based therapies while circumventing ethical concerns associated with embryonic stem cells. By December 2024, 115 clinical trials involving 83 human pluripotent stem cell products had been approved globally, with over 1,200 patients treated, primarily targeting ocular, neurological, and oncological conditions. Recent breakthroughs include Phase I/II trials of iPSC-derived dopaminergic progenitors for Parkinson’s disease, advancement of bemdaneprocel to Phase III trials, and successful corneal endothelial substitutes for bullous keratopathy. iPSC-derived natural killer cells engineered with chimeric antigen receptors show enhanced antitumor effects for both solid tumors and hematological malignancies.

Critical safety challenges remain, including functional maturation of iPSC-derived cells, genomic stability during reprogramming and expansion, and tumorigenicity risks from residual undifferentiated cells. Addressing these concerns, researchers have developed enhanced maturation protocols combining extended cultivation, metabolic signaling, 3D scaffolding, and co-culture techniques. Genomic stability is now monitored through stratified frameworks employing karyotyping, high-density arrays, and whole-genome sequencing, complemented by emerging technologies like optical genome mapping. Tumorigenicity controls utilize advanced detection methods including qPCR targeting pluripotency markers, flow cytometry, and refined in vivo models, along with safety mechanisms such as inducible caspase-9 systems.

The future of iPSC therapies requires balanced innovation with rigorous safety measures, comprehensive registries for outcomes tracking, standardized potency protocols, and global regulatory harmonization. Through careful implementation of maturation enhancements, stability safeguards, and risk mitigation strategies, iPSC therapies continue advancing from laboratory promise to clinical reality.