Hypoxic preconditioning improves the survival and pro-angiogenic capacity of transplanted human umbilical cord mesenchymal stem cells via HIF-1a signaling in a rat model of bronchopulmonary dysplasia

作者全名："Hao, Chang; You, Jingyi; Qiu, Huijun; Zhou, Ou; Liu, Jiang; Zou, Wenjing; Yang, Ke; Fu, Zhou; Zou, Lin"

作者地址："[Hao, Chang; You, Jingyi; Qiu, Huijun; Zhou, Ou; Liu, Jiang; Zou, Wenjing; Yang, Ke; Fu, Zhou; Zou, Lin] Chongqing Med Univ, Pediat Res Inst,Chongqing Engn Res Ctr Stem Cell, Minist Educ,Natl Clin Res Ctr Child Hlth & Disord, Key Lab Child Dev & Disorders,China Int Sci & Tec, Chongqing 400014, Peoples R China; [Hao, Chang; You, Jingyi; Qiu, Huijun; Zhou, Ou; Liu, Jiang; Zou, Wenjing; Fu, Zhou] Chongqing Med Univ, Dept Resp Med, Childrens Hosp, 136 Zhong Shan 2nd Rd, Chongqing 400014, Peoples R China; [Zou, Lin] Chongqing Med Univ, Dept Clin Mol Med, Childrens Hosp, Chongqing 400014, Peoples R China; [Zou, Lin] Shanghai Jiao Tong Univ, Childrens Hosp, Clin Res Unit, Sch Med, Shanghai 200062, Peoples R China; [Zou, Lin] Shanghai Jiao Tong Univ, Inst Pediat Infect Immun & Crit Care Med, Sch Med, Shanghai 200062, Peoples R China"

通信作者："Fu, Z (通讯作者)，Chongqing Med Univ, Dept Resp Med, Childrens Hosp, 136 Zhong Shan 2nd Rd, Chongqing 400014, Peoples R China.; Zou, L (通讯作者)，Shanghai Jiao Tong Univ, Childrens Hosp, Clin Res Unit, Sch Med, Shanghai 200062, Peoples R China.; Zou, L (通讯作者)，Shanghai Jiao Tong Univ, Childrens Hosp, Inst Pediat Infect Immun & Crit Care Med, Sch Med, Shanghai 200062, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000791299100003

JCR分区：Q2

影响因子：3.1

年份：2022

卷号：605

期号：　

开始页：111

结束页：118

文献类型：Article

关键词：Hypoxic preconditioning; Umbilical cord mesenchymal stem cells; Bronchopulmonary dysplasia

摘要："Bronchopulmonary dysplasia (BPD) is a serious chronic respiratory disease that predominates in the neonatal period. Currently, efficacious and effective specific treatments are lacking. Mesenchymal stem cells (MSCs) transplantation has emerged as a promising option for treating BPD. However, the lower cell survival rate limits its therapeutic efficacy. Hypoxic preconditioning is a direct and effective strategy for promoting MSCs survival, proliferation, and paracrine secretion in the recipient after transplantation, which is greatly important to tissue engineering. We investigated whether hypoxia-pretreated MSCs (HPMSCs) confer superior benefit in an experimental BPD rat model. Neonatal Sprague-Dawley rats were exposed to 80-85% O2 for 14 days. Before tracheal transplantation, the MSCs were pretreated for 48 h with deferoxamine, a chemical hypoxia-mimicking agent. In vitro, the HPMSCs reduced the apoptosis rare, caspase-3 expression, and reactive oxygen species (ROS) generation and promoted proliferation, hypoxia inducible factor-1 alpha (HIF-1 alpha ) expression, VEGF secretion, and human umbilical vein endothelial cell tube formation (p < 0.05). In vivo, the HPMSCs restored alveolar structure and lung function, ameliorated pulmonary hypertension, increased vessel density in the BPD rat model (p < 0.05). This work demonstrates for the first time that HPMSCs could have a markedly improved therapeutic effect in BPD, presenting a new potential strategy for the clinical implementation of stem cell biotechnology. (C)& nbsp;2022 Elsevier Inc. All rights reserved."

基金机构：Chongqing Science and Technology Commission [2018ZDXM041]; Chongqing Health Commission

基金资助正文：Acknowledgments This work was supported by the grants from Chongqing Science and Technology Commission and Chongqing Health Commission (2018ZDXM041) .