hiPSC-derived NSCs effectively promote the functional recovery of acute spinal cord injury in mice

Stem Cell Research & Therapy

Baofeng Feng¹  Boxin Liu¹  Asiamah Ernest Amponsah¹  Jingjing He¹  Xin Liu¹  Ruiyun Guo¹  Xiaofeng Du¹  Shuhan Zhang¹  Fei Lv¹  Desheng Kong¹  Huixian Cui²  Jun Ma² 

[1] Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, 050017, Shijiazhuang, Hebei Province, China;Hebei Research Center for Stem Cell Medical Translational Engineering, 050017, Shijiazhuang, Hebei Province, China;Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, 050017, Shijiazhuang, Hebei Province, China;Hebei Research Center for Stem Cell Medical Translational Engineering, 050017, Shijiazhuang, Hebei Province, China;Human Anatomy Department, Hebei Medical University, 050017, Shijiazhuang, Hebei Province, China;

关键词: Spinal cord injury;    Induced pluripotent stem cell;    Neural stem cell;    Mesenchymal stem cell;   

DOI  :  10.1186/s13287-021-02217-9

来源: Springer

【 摘 要 】

BackgroundSpinal cord injury (SCI) is a common disease that results in motor and sensory disorders and even lifelong paralysis. The transplantation of stem cells, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), or subsequently generated stem/progenitor cells, is predicted to be a promising treatment for SCI. In this study, we aimed to investigate effect of human iPSC-derived neural stem cells (hiPSC-NSCs) and umbilical cord-derived MSCs (huMSCs) in a mouse model of acute SCI.MethodsAcute SCI mice model were established and were randomly treated as phosphate-buffered saline (PBS) (control group), repaired with 1 × 105 hiPSC-NSCs (NSC group), and 1 × 105 huMSCs (MSC group), respectively, in a total of 54 mice (n = 18 each). Hind limb motor function was evaluated in open-field tests using the Basso Mouse Scale (BMS) at days post-operation (dpo) 1, 3, 5, and 7 after spinal cord injury, and weekly thereafter. Spinal cord and serum samples were harvested at dpo 7, 14, and 21. Haematoxylin-eosin (H&E) staining and Masson staining were used to evaluate the morphological changes and fibrosis area. The differentiation of the transplanted cells in vivo was evaluated with immunohistochemical staining.ResultsThe hiPSC-NSC-treated group presented a significantly smaller glial fibrillary acidic protein (GFAP) positive area than MSC-treated mice at all time points. Additionally, MSC-transplanted mice had a similar GFAP+ area to mice receiving PBS. At dpo 14, the immunostained hiPSC-NSCs were positive for SRY-related high-mobility-group (HMG)-box protein-2 (SOX2). Furthermore, the transplanted hiPSC-NSCs differentiated into GFAP-positive astrocytes and beta-III tubulin-positive neurons, whereas the transplanted huMSCs differentiated into GFAP-positive astrocytes. In addition, hiPSC-NSC transplantation reduced fibrosis formation and the inflammation level. Compared with the control or huMSC transplanted group, the group with transplantation of hiPSC-NSCs exhibited significantly improved behaviours, particularly limb coordination.ConclusionsHiPSC-NSCs promote functional recovery in mice with acute SCI by replacing missing neurons and attenuating fibrosis, glial scar formation, and inflammation.Graphical abstract

【 授权许可】

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