A comparative study of three different types of stem cells for treatment of rat spinal cord injury.

Abstract Three different sources of human stem cells a#8211; bone marrow mesenchymal stem cells (MSCs), and two neural progenitors (NPs) derived from immortalized spinal fetal cell line (SPC 01), or induced pluripotent stem cells (iPS-NPs) a#8211; were compared in the treatment of a balloon-induced spinal cord compression lesion in rats. One week after lesioning, the rats received either MSCs (intrathecally) or NPs (SPC-01 cells, or iPS-NPs, intraspinally), or saline. The rats were assessed for their locomotor skills (BBB, flat beam test, rotarod). Morphometric analyses of spared white and grey matter, axonal sprouting and glial scar formation, as well as qPCR and Luminex assay were conducted to detect endogenous gene expression, while inflammatory cytokine levels were performed to evaluate the host tissue response to stem cell therapy. The highest locomotor recovery was observed in iPS-NP-grafted animals, which also displayed the highest amount of preserved white and grey matter. Grafted iPS-NPs and SPC-01 cells significantly increased the number of GAP43+ axons, reduced astrogliosis, downregulated Casp 3 expression and increased IL-6 and IL-12 levels. hMSCs transiently decreased levels of inflammatory IL-2 and TNF-a#945;. These findings correlate with the hMSCs short survival, while NPs survived for 2 months and matured slowly into glia and tissue specific neuronal precursors. SPC-01 cells differentiated more in astroglial phenotypes with dense structure of the implant, whereas iPS-NPs displayed a more neuronal phenotype with loose structure of the graft. We concluded that the BBB scores of iPSNPs and hMSC injected rats were superior to the SPC-01 treated group. The iPS-NP treatment of spinal cord injury (SCI) provided the highest recovery of locomotor function due to robust graft survival, and its effect on tissue sparing, reduction of glial scarring and increased axonal sprouting.