title: Umbilical cord blood cells regulate the differentiation of endogenous neural stem cells in hypoxic ischemic neonatal rats via the hedgehog signaling pathway.
abstract: 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.
authors.affiliation: Department of Medical Imaging, Weifang Medical University, Weifang, Shandong, China. Electronic address: wxlpine@163.com.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Weifang Medical University Affiliated Hospital, Clinical Institute, Weifang Medical University, Weifang, Shandong, China.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Brigham and Women׳s Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: xwang@rics.bwh.harvard.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000150:complications; D002540:Cerebral Cortex / Q000503:physiopathology; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000071676:Zinc Finger Protein GLI1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055415:Bone Morphogenetic Protein 4; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000071676:Zinc Finger Protein GLI1; C525811:Bmp4 protein, rat; C498521:Gli1 protein, rat; C546888:Shh protein, rat; C510879:neurogenin-1, rat
keywords: Differentiation; HIBD; Hedgehog; Neural stem cell; Umbilical cord blood mononuclear cells