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Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury.

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Li, Qian 
Liu, Sumei 
Zheng, Tianqi 
Li, Mo 
Qi, Boling 


BACKGROUND: Spinal cord injury (SCI) is a devastating disease that causes extensive damage to oligodendrocytes and neurons leading to demyelination and axonal degeneration. In this study, we co-transplanted cell grafts containing oligodendrocyte progenitor cells (OPCs) derived from human-induced pluripotent stem cells (iPSCs) combined with human umbilical vein endothelial cells (HUVECs), which were reported to promote OPCs survival and migration, into rat contusion models to promote functional recovery after SCI. METHODS: OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo. RESULTS: Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery. CONCLUSIONS: Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.


Acknowledgements: We would like to thank Prof. Yuejun Chen for the gift of hESC-EGFP.


HUVECs, Induced pluripotent stem cells, Oligodendrocyte progenitor cells, Spinal cord injury, Rats, Humans, Animals, Oligodendrocyte Precursor Cells, Human Umbilical Vein Endothelial Cells, Recovery of Function, Induced Pluripotent Stem Cells, Spinal Cord Injuries, Oligodendroglia, Spinal Cord, Cell Differentiation

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Stem Cell Res Ther

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Springer Science and Business Media LLC
Stem Cell and Translation National Key Project (2016YFA0101403)
National Natural Science Foundation of China (82171250, 81973351)
Beijing Municipal Natural Science Foundation (5142005)
Beijing Talents Foundation (2017000021223TD03)
Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan (CIT, TCD20180333)
Beijing Municipal Health Commission Fund (PXM2020_026283_000005)
Beijing One Hundred, Thousand, and Ten Thousand Talents Fund (2018A03)
Royal Society-Newton Advanced Fellowship (NA150482)
National Science Foundation for Young Scientists of China (31900740)