Umbilical cord blood cells regulate the differentiation of endogenous neural stem cells in hypoxic ischemic neonatal rats via the hedgehog signaling pathway.
Transplantation of umbilical cord blood mononuclear cells (UCBMC) promotes the proliferation of endogenous neural stem cells (NSCs), but it has been unclear whether the proliferating NSCs can differentiate into mature neural cells. Therefore, we explored the effects of UCBMC transplantation on the differentiation of endogenous NSCs and their underlying mechanisms. Seven-day-old Sprague-Dawley rats underwent left carotid ligation followed by hypoxic stress. UCBMC were transplanted 24h after hypoxia ischemia (HI). BrdU/β-tubulin/HNA/DAPI, BrdU/GFAP/HNA/DAPI, Ngn1/DAPI, and BMP4/DAPI were measured by immunofluorescence staining; Shh, Gli1, Ngn1, and BMP4 proteins were measured by western-blot analysis 28 days after transplantation. More newborn neurons and fewer astrocytes were observed in the HI+UCBMC group, its neuronal percentage was higher, and glial percentage was lower compared with the N+UCBMC (P<0.05) and HI+PBS groups (P<0.01), while fewer newborn neurons and more newborn astrocytes were found in the HI+cyclopamine (an antagonist of the hedgehog protein)+UCBMC group compared with the HI+UCBMC group (P<0.01). The expression of Shh, Gli1, and Ngn1 proteins was higher and BMP4 protein was lower in the HI+UCBMC compared with the HI+PBS group (P<0.01) and the HI+cyclopamine+UCBMC group (P<0.01). Linear regression analysis showed that the differentiation of NSCs correlated with expression of Ngn1 and BMP4 proteins (P<0.01). In conclusion, UCBMC promote neuronal differentiation and reduce glial differentiation in hypoxic ischemic neonatal rats via the hedgehog signaling pathway.
['Wang|Xiaoli|X|', 'Zhao|Yansong|Y|', 'Wang|Xin|X|']
D000818:Animals D001253:Astrocytes D051792:Basic Helix-Loop-Helix Transcription Factors D055415:Bone Morphogenetic Protein 4 D002340:Carotid Artery Diseases D002540:Cerebral Cortex D036101:Cord Blood Stem Cell Transplantation D005260:Female D053823:Hedgehog Proteins D006412:Hematopoietic Stem Cells D020925:Hypoxia-Ischemia, Brain D051741:Kruppel-Like Transcription Factors D008297:Male D009419:Nerve Tissue Proteins D058953:Neural Stem Cells D055495:Neurogenesis D017207:Rats, Sprague-Dawley D015398:Signal Transduction D000071676:Zinc Finger Protein GLI1
Differentiation Neural stem cell Hedgehog Umbilical cord blood mononuclear cells HIBD