Transplantation of Human Umbilical Mesenchymal Stem Cells from Wharton's Jelly after Complete Transection of the Rat Spinal Cord

Abstract

BackgroundHuman umbilical mesenchymal stem cells (HUMSCs) isolated from Wharton's jelly of the umbilical cord can be easily obtained and processed compared with embryonic or bone marrow stem cells. These cells may be a valuable source in the repair of spinal cord injury.Methodology/Principal FindingsWe examine the effects of HUMSC transplantation after complete spinal cord transection in rats. Approximately 5×105 HUMSCs were transplanted into the lesion site. Three groups of rats were implanted with either untreated HUMSCs (referred to as the stem cell group), or HUMSCs treated with neuronal conditioned medium (NCM) for either three days or six days (referred to as NCM-3 and NCM-6 days, respectively). The control group received no HUMSCs in the transected spinal cord. Three weeks after transplantation, significant improvements in locomotion were observed in all the three groups receiving HUMSCs (stem cell, NCM-3 and NCM-6 days groups). This recovery was accompanied by increased numbers of regenerated axons in the corticospinal tract and neurofilament-positive fibers around the lesion site. There were fewer microglia and reactive astrocytes in both the rostral and caudal stumps of the spinal cord in the stem cell group than in the control group. Transplanted HUMSCs survived for 16 weeks and produced large amounts of human neutrophil-activating protein-2, neurotrophin-3, basic fibroblast growth factor, glucocorticoid induced tumor necrosis factor receptor, and vascular endothelial growth factor receptor 3 in the host spinal cord, which may help spinal cord repair.Conclusions/SignificanceTransplantation of HUMSCs is beneficial to wound healing after spinal cord injury in rats.

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

“…HMSCs isolated from Wharton's jelly can be easily and ethically obtained and processed compared with embryonic or bone marrow stem cells. These stem cells may be a valuable source in the repair of the peripheral nervous system with capacity to differentiate into neuroglial-like cells ( Fu et al, 2006;Yang et al, 2008). The transplanted HMSCs were also able to promote local blood vessel formation and release the neuro-trophic factors brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) ( Fu et al, 2006;Wang et al, 2004).…”

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

“…Yang et al reported that the transplantation of 5 × 10 5 hUC-MSCs at the lesion site after complete transection of the rat spinal cord promoted significant recovery of locomotion, stimulated the regrowth of injured corticospinal fibers, and increased the number of neurofilament-positive axons around the lesion site (6). Of note, these neuroprotective effects were associated with immunomodulation (a decrease in the microglial and astrocytic responses) and with increased Review Dalous et al levels of human growth factors such as basic fibroblast growth factor and NT-3.…”

“…Several reports have demonstrated neuroprotection after experimental hUC-MSC xenotransplantation with or without immunosuppressive treatment, and there is no consensus as to the need for immunosuppression for optimal neuroprotection. 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).…”

“…A few promising experimental studies using human UCB (hUCB)-derived mononuclear cells and hUC-derived mesenchymal stem cells (hUC-MSCs), either from the blood or from Wharton's jelly, have already been undertaken (5)(6)(7)(8). Thus, there is increasing interest in studying the potential of UC-derived stem cells for the treatment of brain diseases (9).…”

Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation

“…It has been postulated that this neuroprotection may occur as a result of growth factor production by transplanted cells, and this theory is supported by transfection studies with growth factors such as glial cell line derived neurotrophic factor that have been shown to improve functional recovery after stroke in a rodent model (12). The other options may be inhibition of the host immune response and inflammation (20,23), improvement of vascularization (5) and suppression of glial scar formation (23). Alternatively, functional recovery could be elicited by axon growth and neural plasticity-promoting approaches that result in restoration of damaged and formation of new neural circuits that could become involved in functional recovery (5, 8,16).…”