Cografted Wharton’s Jelly Cells-derived Neurospheres and BDNF Promote Functional Recovery After Rat Spinal Cord Transection

Abstract

An animal model of transected spinal cord injury (SCI) was used to test the hypothesis that cografted human umbilical mesenchymal stem cells-derived neurospheres (HUMSC-NSs) and BDNF can promote morphologic and functional recoveries of injured spinal cord. In vitro, HUMSC-NSs terminally differentiated into higher percentages of cells expressing neuronal markers: beta-tubulin III and MAP2ab by the supplement with BDNF. Following grafted into injured spinal cord, very few grafted cells survived in the HUMSC-NSs + BDNF-treated (<3%) and HUMSC-NSs-treated (<1%) groups. The survived cells were differentiated into various cells, which were confirmed by double staining of BrdU and neural or glia markers. In comparison, more grafted cells in the HUMSC-NSs + BDNF group transformed into mature neural-like cells, while more grafted cells in the HUMSC-NSs group transformed into oligodendrocyte-like cells. HUMSC-NSs + BDNF-treated group had more greatly improved BBB scores, compared with HUMSC-NSs-treated and medium-treated groups. Additionally, axonal regeneration showed significant improvement in rats receiving HUMSC-NSs + BDNF, compared with HUMSC-NSs-treated and medium-treated groups, as demonstrated by the NF-200-positive staining and Fluorogold (FG) retrograde tracing study. Lastly, a significant reduction in the percentage cavitation was seen in the two cell-treated groups compared with medium control group. These results means BDNF could promote the neural differentiation of HUMSC-NSs in vitro and in vivo. However, cellular replacement is unlikely to explain the improvement in functional outcome. The functional recovery might more rely on the axonal regeneration and neuroprotective action that active by the grafted cells. Cografted HUMSCs and BDNF is a potential therapy for SCI.

Transplantation of umbilical cord–derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives

“…Some studies have shown the survival of numerous transplanted cells for periods as long as 4 mo, even though no immunosuppression was used (6,59,97). Contrarily, in similar animal models, few transplanted cells could be identified a few weeks after transplantation in immunosuppressed animals (98). Further studies are therefore required to clarify whether immunosuppression is a help or a hindrance in obtaining the most beneficial outcomes in xenotransplantation experiments.…”

Mesenchymal stem cells in the treatment of spinal cord injuries: A review

“…Zhang et al [83] , used an animal model of transected SCI to test the hypothesis that cografted human umbilical mesenchymal stem cells-derived neurospheres (HUMSC-NSs) and BDNF can promote morphologic and functional recoveries of the injured spinal cord. Recovery of hindlimb locomotor function in SCI rats was significantly enhanced in human umbilical cord mesenchymal stem cells-grafted animals at five weeks as compared to control sham-grafted animals [84] .…”

Stem cell therapies in the treatment of diabetic retinopathy and keratopathy

“…In this respect, it is worth mentioning that MSCs can self-renew and differentiate into tissues of mesodermal origin. 37,38 However, some data also suggest their ability to turn into other cell types, such as glial and neural cells, [46][47][48][49] or pancreatic [50][51][52] and hepatocyte-like cells. 53,54 Despite considerable debate regarding the ability of MSCderived cells to express markers' characteristic for fully differentiated ecto-and endodermal lineages, there is growing evidence supporting MSCs potential for generating cell types of multiple lineages suitable for cell therapy in various degenerative and metabolic conditions, including diabetes (reviewed in literatures 32,55,56 ).…”