TY - JOUR
KW - Axon growth
KW - glial cells
KW - iPSCs
KW - Neural repair
KW - Neuromuscular junctions
KW - Organoids and assembloids
KW - Regeneration
AU - Manasi Agrawal
AU - Meghal Desai
AU - Shruti Ghumra
AU - Yashashree Bhorkar
AU - Pabitra K. Sahoo
AB - Injuries and degenerative diseases of the human nervous system result in irreversible functional loss, reflecting the limited regenerative capacity of the central nervous system and the slow repair rate of the peripheral nervous system. Progress has been hindered by the lack of human-relevant experimental models that accurately capture the cellular diversity, long axonal architecture, and species-specific regulatory mechanisms underlying neural injury and repair. Human induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to bridge this gap, enabling the generation of diverse neuronal and glial subtypes, reconstruction of complex neural circuits, and modeling of injury and regeneration in a human-specific context. In this review, we discuss the recent advances in the use of human iPSC-derived systems to study neural repair, spanning two-dimensional cultures, three-dimensional organoids and assembloids, microengineered axon injury platforms, and in vivo transplantation models. We highlight how these approaches have revealed key intracellular regulators of neurite growth, clarified the impact of disease-associated mutations on axonal integrity, and enabled high-throughput screening of neuroprotective and pro-regenerative compounds. We further discuss the role of iPSC-derived glial cells, Schwann cells, and neuromuscular junction models in elucidating axon-glia interactions, remyelination, and circuit-level repair mechanisms. Together, human iPSC-based models offer unprecedented insight into the cellular and molecular determinants of human neural regeneration, thereby overcoming the limitations of animal systems. While challenges remain in standardization, maturation, and clinical translation, these platforms are redefining regenerative neuroscience and hold promise for the development of patient-specific therapies aimed at restoring function after nervous system injury.
BT - Progress in Neurobiology
DA - 2026-05-01
DO - 10.1016/j.pneurobio.2026.102907
N2 - Injuries and degenerative diseases of the human nervous system result in irreversible functional loss, reflecting the limited regenerative capacity of the central nervous system and the slow repair rate of the peripheral nervous system. Progress has been hindered by the lack of human-relevant experimental models that accurately capture the cellular diversity, long axonal architecture, and species-specific regulatory mechanisms underlying neural injury and repair. Human induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to bridge this gap, enabling the generation of diverse neuronal and glial subtypes, reconstruction of complex neural circuits, and modeling of injury and regeneration in a human-specific context. In this review, we discuss the recent advances in the use of human iPSC-derived systems to study neural repair, spanning two-dimensional cultures, three-dimensional organoids and assembloids, microengineered axon injury platforms, and in vivo transplantation models. We highlight how these approaches have revealed key intracellular regulators of neurite growth, clarified the impact of disease-associated mutations on axonal integrity, and enabled high-throughput screening of neuroprotective and pro-regenerative compounds. We further discuss the role of iPSC-derived glial cells, Schwann cells, and neuromuscular junction models in elucidating axon-glia interactions, remyelination, and circuit-level repair mechanisms. Together, human iPSC-based models offer unprecedented insight into the cellular and molecular determinants of human neural regeneration, thereby overcoming the limitations of animal systems. While challenges remain in standardization, maturation, and clinical translation, these platforms are redefining regenerative neuroscience and hold promise for the development of patient-specific therapies aimed at restoring function after nervous system injury.
PY - 2026
EP - 102907
T2 - Progress in Neurobiology
TI - Human induced pluripotent stem cell-based models for studying neural repair
UR - https://www.sciencedirect.com/science/article/pii/S030100822600033X
VL - 260
Y2 - 2026-03-23
SN - 0301-0082
ER -