Functional recovery by transplantation of human iPSC-derived A2B5 positive neural progenitor cell after spinal cord injury in mice.
Article
Zheng, Yiyan, Chen, Xiaohui, Bu, Ping et al. (2025). Functional recovery by transplantation of human iPSC-derived A2B5 positive neural progenitor cell after spinal cord injury in mice.
. 10.1101/2025.08.12.669912
Zheng, Yiyan, Chen, Xiaohui, Bu, Ping et al. (2025). Functional recovery by transplantation of human iPSC-derived A2B5 positive neural progenitor cell after spinal cord injury in mice.
. 10.1101/2025.08.12.669912
Human induced pluripotent stem cells (hiPSCs) hold great potential for patient-specific therapies. Transplantation of hiPSC-derived neural progenitor cells (NPCs) is a promising reparative strategy for spinal cord injury (SCI), but clinical translation requires efficient differentiation into desired neural lineages and purification before transplantation. Here, differentiated hiPSCs-reprogrammed from human skin fibroblasts using Sendai virus-mediated expression of OCT4, SOX2, KLF4, and C-MYC-into neural rosettes expressing SOX1 and PAX6, followed by neuronal precursors (β-tubulin III⁺/NESTIN⁺) and glial precursors (GFAP⁺/NESTIN⁺). Both neuronal and glial precursors expressed the A2B5 surface antigen. A2B5+ NPCs, purified by fluorescence-activated cell sorting (FACS), proliferated in vitro with mitogens and differentiated into mature neurons and astrocytes under lineage-specific conditions. NOD-SCID mice received a T9 contusion injury followed by transplantation of A2B5+ NPCs, human fibroblasts, or control medium at 8 days post-injury. At two months, grafted NPCs showed robust survival, progressive neuronal maturation (β-tubulin III⁺ → doublecortin⁺ → NeuN⁺), and astrocytic differentiation (GFAP⁺), particularly in spared white matter. Transplantation significantly increased spared white matter volume and improved hindlimb locomotor recovery, with no teratoma formation observed. These results demonstrate that hiPSC-derived, FACS-purified A2B5+ NPCs can survive, differentiate into neurons and astrocytes, and enhance functional recovery after SCI. This approach offers a safe and effective candidate cell source for treating SCI and potentially other neurological disorders.
