title: Umbilical cord blood mesenchymal stem cells co-modified by TERT and BDNF: a novel neuroprotective therapy for neonatal hypoxic-ischemic brain damage.
abstract: Hypoxic-ischemic brain damage (HIBD), a leading cause of perinatal disability and death, has limited therapeutic options. Stem cell therapy has been demonstrated as a potential novel therapy for neurological disorders. Compared with other types of stem cells, umbilical cord blood mesenchymal stem cells (UCB-MSCs) have several unique characteristics, such as a higher rate of cell proliferation and clonality. However, the limited life span of UCB-MSCs hinders their clinical application. Therefore, efforts are urgently needed to circumvent this disadvantage. Telomerase reverse transcriptase (TERT), which promotes cell proliferation and survival, plays a protective role in hypoxic-ischemic (HI) brain injury. Thus, it is reasonable to propose that UCB-MSCs modified by exogenous TERT expression might have a longer lifespan and increased viability. Moreover, brain-derived neurotrophic factor (BDNF), a neurotrophin that regulates development, regeneration, survival and maintenance of neurons, facilitates post-injury recovery when administered by infusion or virus-mediated delivery. Therefore, TERT- and BDNF-modified UCB-MSCs may have a longer lifespan and also maintain neural differentiation, thus promoting the recovery of neurological function following hypoxic-ischemic brain damage (HIBD) and thereby representing a new effective strategy for HIBD in neonates.
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu 610041, China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu 610041, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu 610041, China.
authors.forename: Haiting
authors.initials: H
authors.lastname: Liu
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
authors.forename: Baowen
authors.initials: B
authors.lastname: Du
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu 610041, China; Department of Pediatrics and Neurology, University of California, San Francisco, CA 94143, USA. Electronic address: mudz@scu.edu.cn.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Mu
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000628:therapy*; D007231:Infant, Newborn; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D019098:Telomerase / Q000627:therapeutic use*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D019098:Telomerase
keywords: Brain-derived neurotrophic factor; Hypoxic-ischemic brain damage; Telomerase reverse transcriptase; Umbilical cord blood mesenchymal stem cells