PMID- 35003786
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220429
IS  - 2081-3856 (Print)
IS  - 2081-6936 (Electronic)
IS  - 2081-6936 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Jan 1
TI  - Bone marrow mesenchymal stem cells overexpressing hepatocyte growth factor 
      ameliorate hypoxic-ischemic brain damage in neonatal rats.
PG  - 561-572
LID - 10.1515/tnsci-2020-0204 [doi]
AB  - OBJECTIVES: Hypoxic-ischemic brain damage (HIBD) is a major cause of brain injury 
      in neonates. Bone marrow mesenchymal stem cells (BMSCs) show therapeutic 
      potential for HIBD, and genetic modification may enhance their neuroprotective 
      effects. The goal of this study was to investigate the neuroprotective effects of 
      hepatocyte growth factor (HGF)-overexpressing BMSCs (BMSCs-HGF) against HIBD and 
      their underlying mechanisms. METHODS: BMSCs were transfected with HGF using 
      adenoviral vectors. HIBD models were established and then BMSCs were transplanted 
      into the brains of HIBD rats via intraventricular injection. 
      2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to measure cerebral 
      infarction volumes. In vitro, primary cultured cortical neurons were co-cultured 
      with BMSCs in a Transwell plate system. Oxygen-glucose deprivation (OGD) was 
      applied to imitate hypoxic-ischemic insult, and PD98059 was added to the culture 
      medium to block the phosphorylation of extracellular signal-regulated kinase 
      (ERK). Cell apoptosis was determined using TUNEL staining. The expression of HGF 
      was measured by immunofluorescence, real-time quantitative PCR (RT-qPCR), and 
      western blots. The expression of phosphorylated ERK (p-ERK) and B-cell lymphoma-2 
      (Bcl-2) was measured by western blots. RESULTS: HGF-gene transfection promoted 
      BMSC proliferation. Moreover, BMSCs-HGF decreased HIBD-induced cerebral 
      infarction volumes and enhanced the protective effects of the BMSCs against HIBD. 
      BMSCs-HGF also increased expression of HGF, p-ERK, and Bcl-2 in brain tissues. In 
      vitro, BMSC-HGF protected neurons against OGD-induced apoptosis. Inhibition of 
      ERK phosphorylation abolished the neuroprotective effect of BMSCs-HGF against 
      OGD. CONCLUSIONS: BMSCs-HGF is a potential treatment for HIBD and that the 
      ERK/Bcl-2 pathway is involved in the underlying neuroprotective mechanism.
CI  - (c) 2021 Wen Zeng et al., published by De Gruyter.
FAU - Zeng, Wen
AU  - Zeng W
AD  - Department of Neonatology, Chengdu Women's and Children's Central Hospital, 
      School of Medicine, University of Electronic Science and Technology of China, 
      Chengdu, 611731, Sichuan, China.
FAU - Wang, Yu
AU  - Wang Y
AD  - Department of Neonatology, Chengdu Women's and Children's Central Hospital, 
      School of Medicine, University of Electronic Science and Technology of China, 
      Chengdu, 611731, Sichuan, China.
FAU - Xi, Yufeng
AU  - Xi Y
AD  - Department of Neonatology, Chengdu Women's and Children's Central Hospital, 
      School of Medicine, University of Electronic Science and Technology of China, 
      Chengdu, 611731, Sichuan, China.
FAU - Wei, Guoqing
AU  - Wei G
AD  - Department of Neonatology, Chengdu Women's and Children's Central Hospital, 
      School of Medicine, University of Electronic Science and Technology of China, 
      Chengdu, 611731, Sichuan, China.
FAU - Ju, Rong
AU  - Ju R
AD  - Department of Neonatology, Chengdu Women's and Children's Central Hospital, 
      School of Medicine, University of Electronic Science and Technology of China, 
      Chengdu, 611731, Sichuan, China.
LA  - eng
PT  - Journal Article
DEP - 20211217
PL  - Germany
TA  - Transl Neurosci
JT  - Translational neuroscience
JID - 101550327
PMC - PMC8684041
OTO - NOTNLM
OT  - adenoviral vector
OT  - bone marrow mesenchymal stem cell
OT  - extracellular signal-regulated kinase
OT  - hepatocyte growth factor
OT  - hypoxic-ischemic brain damage
COIS- Conflict of interest: The authors state no conflict of interest.
EDAT- 2022/01/11 06:00
MHDA- 2022/01/11 06:01
PMCR- 2021/12/17
CRDT- 2022/01/10 09:18
PHST- 2021/09/22 00:00 [received]
PHST- 2021/12/01 00:00 [revised]
PHST- 2021/12/01 00:00 [accepted]
PHST- 2022/01/10 09:18 [entrez]
PHST- 2022/01/11 06:00 [pubmed]
PHST- 2022/01/11 06:01 [medline]
PHST- 2021/12/17 00:00 [pmc-release]
AID - tnsci-2020-0204 [pii]
AID - 10.1515/tnsci-2020-0204 [doi]
PST - epublish
SO  - Transl Neurosci. 2021 Dec 17;12(1):561-572. doi: 10.1515/tnsci-2020-0204. 
      eCollection 2021 Jan 1.