Astrocyte-like cells derived from human oral mucosa stem cells provide neuroprotection in vitro and in vivo.
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.
Neurosciences Laboratory, Felsenstein Medical Research Center-Rabin Medical Center, Sackler Faculty of Medicine, and Oral Biology Department, School of Dental Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Oral and Maxillofacial Department, Baruch Padeh Medical Center, Poria, Lower Galilee, Israel.
Javier
J
Ganz
Ina
I
Arie
Tali
T
Ben-Zur
Michal
M
Dadon-Nachum
Sammy
S
Pour
Shareef
S
Araidy
Sandu
S
Pitaru
Daniel
D
Offen
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002038:Bungarotoxins / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008297:Male; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009061:Mouth Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009469:Neuromuscular Junction; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016708:Synaptophysin / Q000737:chemistry
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D002038:Bungarotoxins; D017077:Culture Media, Conditioned; D005904:Glial Fibrillary Acidic Protein; C583557:IGF1 protein, human; D064568:S100 Calcium Binding Protein beta Subunit; D016708:Synaptophysin; D007334:Insulin-Like Growth Factor I; C579455:BDNF protein, human
Astrocytes; Cell therapy; Neural differentiation; Oral mucosa stem cells