Astrocyte-Like Cells Derived From Human Oral Mucosa Stem Cells Provide Neuroprotection In Vitro and In Vivo

Abstract

Human oral mucosa stem cells (hOMSC) are a recently described neural crest-derived stem cell population. Therapeutic quantities of potent hOMSC can be generated from small biopsies obtained by minimally invasive procedures. Our objective was to evaluate the potential of hOMSC to differentiate into astrocyte-like cells and provide peripheral neuroprotection. We induced hOMSC differentiation into cells showing an astrocyte-like morphology that expressed characteristic astrocyte markers as glial fibrillary acidic protein, S100β, and the excitatory amino acid transporter 1 and secreted neurotrophic factors (NTF) such as brain-derived neurotrophic factor, vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor 1. Conditioned medium of the induced cells rescued motor neurons from hypoxia or oxidative stress in vitro, suggesting a neuroprotective effect mediated by soluble factors. Given the neuronal support (NS) ability of the cells, the differentiated cells were termed hOMSC-NS. Rats subjected to sciatic nerve injury and transplanted with hOMSC-NS showed improved motor function after transplantation. At the graft site we found the transplanted cells, increased levels of NTF, and a significant preservation of functional neuromuscular junctions, as evidenced by colocalization of α-bungarotoxin and synaptophysin. Our findings show for the first time that hOMSC-NS generated from oral mucosa exhibit neuroprotective effects in vitro and in vivo and point to their future therapeutic use in neural disorders.

Intrastriatal Transplantation of Adult Human Neural Crest-Derived Stem Cells Improves Functional Outcome in Parkinsonian Rats

“…In addition, the site of ITSC migration within the midbrain and near the lesioned SN suggests an impact on the restoration of the lesioned substantia nigra via production of trophic factors. Considering the commonly described expression and secretion of GDNF, NGF or BDNF by mesenchymal stem cells [65, 75] and neural‐crest‐derived stem cells in vivo and in vitro [70, 72, 76], ITSCs may secrete similar neurotrophic factors to restore endogenous DA neuron populations—an interesting matter for more detailed investigation in future studies. Regarding their potential cellular source, endogenous TH + neurons observed after ITSC transplantation may be derived either by differentiation of neural progenitors closely located to the SN, such as ventral midbrain NSCs [77], via dedifferentiation of resident astrocytes [78] or by endogenous DA neurons that have not degenerated in the first place.…”

The Effect of Oral Mucosal Mesenchymal Stem Cells on Long-Term Brain Edema and Lesion, Anxiety-Like Behavior, and Cognitive and Motor Outcomes in Experimental Traumatic Brain Injury

“…OMSCs can differentiate into astrocyte-like cells and are capable of producing neuroprotective factors such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), glia-derived neuroprotective factor (GDNF) and insulin-like growth factor-1 (IGF-1). Considering the neuroprotective effects of these cells in vitro [21] and in vivo [22], their study on the treatment of TBI has been proposed.…”

Human‐ and mouse‐derived neurons can be simultaneously obtained by co‐cultures of human oral mucosal stem cells and mouse neural stem cells

“…The regenerative ability of nasal mucosa stem cells has been recently well proven: in a parkinsonian rat model (Müller et al., ), in an hemi‐parkinsonian rat model (Ganz, Arie, Buch, et al.s, ) and in a spinal cord injury model (Cho et al., ). Moreover, hOMSC in an experimental rat model of sciatic nerve injury revealed a neuroprotective effect, improving the motor function following transplantation (Ganz, Arie, Ben‐Zur, et al., ). The major idea of the current work was to test co‐cultivation of hOMSC and mNSC.…”