Engrafted peripheral blood-derived mesenchymal stem cells promote locomotive recovery in adult rats after spinal cord injury

Spinal cord injury (SCI) is a severe trauma of central nervous system (CNS). Numerous stem cells have been applied for SCI therapy. Peripheral blood-derived mesenchymal stem cells (PBMSCs) have captured researchers' attention by virtue of pluripotency and effectiveness. However, little work has been performed on whether PBMSCs play roles and what role, if any, in the lesion microenvironment. Through the investigation of the differentiation, neuroprotection and immunoloregulation of engrafted PBMSCs, we found that the expression of glial fibrillary acidic protein (GFAP) was inhibited. Meanwhile, myelin basic protein (MBP), neurofilament protein-200 (NF-200) and microtubule associated protein-2 (MAP-2) were promoted after PBMSC transplantation (PBMSCT) by immunohistochemistry. Though engrafted PKH26+PBMSCs could survive in vivo for at least 8 w, they could not respectively express GFAP, MBP and neuronal specific neucleoprotein (NeuN) by immunofluorescence. Additionally, Flow cytometry demonstrated that the number of CD4+IL17+Th17 cells decreased while CD4+CD25+Foxp3+Treg ones increased after PBMSCT (P < 0.01). Immunohistochemistry and Elisa both showed a lower expression of IL-6 and IL-17a while a higher expression of TGF-β after PBMSCT (P < 0.05). RT-PCR indicated that Th17-relevant genes including RORγT, IL-6 and IL-21 were inhibited and resulted in the decrease of IL-23a and IL-22 secretion (P < 0.05); Treg-relevant genes including FoxP3 and TGF-β and the secretion of IL-10 were improved (P < 0.05). Accordingly, we concluded that the PBMSCT-relevant therapy took effect not through the differentiation of PBMSCs into CNS cells, but through regulating Th17/Treg-relevant gene expression, inhibiting Th17-relevant gene expression and meanwhile promoting Treg-relevant gene expression, and eventually resulted in promotion of the functional recovery of SCI rats.

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