Intracerebral transplantation of HLA‐homozygous human iPSC‐derived neural precursors ameliorates the behavioural and pathological deficits in a rodent model of ischaemic stroke
Jeong‐Eun Noh, Seung‐Hun Oh, Suji Lee, Soo Hyun Lee, Young Hoon Kim, Hyun-Jung Park, Ji Hyeon Ju, Hyun Sook Kim, Ji Young Huh, Jihwan Song
Abstract
OBJECTIVES: Human-induced pluripotent stem cells (hiPSCs) are a promising cell source for treating ischaemic stroke. Although autologous hiPSCs provide the advantage of avoiding immune rejection, their practical limitations, such as substantial amount of time and costs to generate individual iPSC lines, have hampered their widespread application in clinical settings. In this study, we investigated the therapeutic potential of neural precursor cells derived from human HLA-homozygous induced pluripotent stem cells (hiPSC-NPCs) following intracerebral transplantation into a rodent model of middle cerebral artery occlusion (MCAo). MATERIALS AND METHODS: We differentiated a GMP-grade HLA-homozygous hiPSC line (CMC-hiPSC-004) into neural precursor cells for transplantation into rats at the subacute stage of ischaemic stroke (ie at 7 days after the induction of MCAo). To investigate functional recovery, the transplanted animals were subjected to five behavioural tests, namely the rotarod, stepping, mNSS, staircase and apomorphine-induced rotation tests, for up to 12 weeks, followed by histological analyses. RESULTS: medium spiny neurons. The transplanted cells formed neuronal connections with striatal neurons in the host brain. In addition, hiPSC-NPC transplantation gave rise to enhanced endogenous repair processes, including decreases of post-stroke neuroinflammation and glial scar formation and an increase of proliferating endogenous neural stem cells in the subventricular zone as well as the perilesional capillary networks. CONCLUSIONS: These results strongly suggest that HLA-homozygous hiPSC-NPCs may be useful for treating ischaemic stroke patients.