title: Overexpression of HIF-1α in mesenchymal stem cells contributes to repairing hypoxic-ischemic brain damage in rats.
abstract: Preclinical researches on mesenchymal stem cells (MSCs) transplantation, which is used to treat hypoxic-ischemic (HI) brain damage, have received inspiring achievements. However, the insufficient migration of active cells to damaged tissues has limited their potential therapeutic effects. There are some evidences that hypoxia inducible factor-1 alpha (HIF-1α) promotes the viability and migration of the cells. Here, we aim to investigate whether overexpression of HIF-1α in MSCs could improve the viability and migration capacity of cells, and its therapeutic efficiency on HI brain damage. In the study, MSCs with HIF-1α overexpression was achieved by recombinant lentiviral vector and transplanted to the rats subsequent to HI. Our data indicated that overexpression of HIF-1α promoted the viability and migration of MSCs, HIF-1α overexpressed MSCs also had a stronger therapeutic efficiency on HI brain damaged treatment by mitigating the injury on behavioral and histological changes evoked by HI insults, accompanied with more MSCs migrating to cerebral damaged area. This study demonstrated that HIF-1α overexpression could increase the MSCs' therapeutic efficiency in HI and the promotion of the cells' directional migration to cerebral HI area by overexpression may be responsible for it, which showed that transplantation of MSCs with HIF-1α overexpression is an attractive therapeutic option to treat HI-induced brain injury in the future.
authors.affiliation: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Deju
authors.initials: D
authors.lastname: Lin
authors.affiliation: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhou
authors.affiliation: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Wang
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliate Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Liu
authors.affiliation: The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cong
authors.affiliation: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Chuanqin
authors.initials: C
authors.lastname: Hu
authors.affiliation: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Ge
authors.affiliation: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. Electronic address: qinyu3587@126.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yu
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D005822:Genetic Vectors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics* / Q000523:psychology / Q000628:therapy*; D008297:Male; D018782:Maze Learning; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: Hypoxia inducible factor-1 alpha; Hypoxic-ischemic brain damage; Mesenchymal stem cell