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中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2023, Vol. 13 ›› Issue (02) : 115 -120. doi: 10.3877/cma.j.issn.2095-1221.2023.02.008

综述

缺氧预处理间充质干细胞的功能及机制研究进展
陈玉婷, 周影, 陆雅斐, 江滨†()   
  1. 210022　南京中医药大学附属南京中医院肛肠科
  • 收稿日期:2022-07-29 出版日期:2023-04-01
  • 通信作者: 江滨
  • 基金资助:
    江苏省研究生科研与实践创新计划(SJCX21_0747); 2022年江苏省科技计划专项资金重点研发计划社会发展面上项目(BE2022674)

Advances in the function and mechanism of hypoxic preconditioned mesenchymal stem cells

Yuting Chen, Ying Zhou, Yafei Lu, Bin Jiang†()   

  1. Department of Anorectal, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, China
  • Received:2022-07-29 Published:2023-04-01
  • Corresponding author: Bin Jiang
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引用本文：

陈玉婷, 周影, 陆雅斐, 江滨. 缺氧预处理间充质干细胞的功能及机制研究进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(02): 115-120.

Yuting Chen, Ying Zhou, Yafei Lu, Bin Jiang. Advances in the function and mechanism of hypoxic preconditioned mesenchymal stem cells[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(02): 115-120.

间充质干细胞（MSCs）具有免疫调节、组织修复和造血等多种生物功能，获得了广泛的关注和研究，是目前再生医学领域研究的热点，但在临床应用中存在移植后存活率低以及功能发挥受限的问题。近年来，利用物理、化学和生物刺激等预处理改善MSCs生物活性的研究取得较大进展，缺氧为其中较为广泛的一种预处理方式。本文就缺氧预处理对MSCs增殖、凋亡、分化、归巢、旁分泌、促进血管生成和免疫功能的影响及机制作一综述。

关键词: 缺氧预处理, 间充质干细胞, 缺氧诱导因子

Mesenchymal stem cells (MSCs) therapy is currently a hot spot in the field of regenerative medicine. It has received extensive attention and research due to its various biological activities such as immune regulation, tissue repair, and hematopoiesis. But in clinical applications, MSCs transplantation faces challenges such as low survival rates and limited functionality. In recent years, great progress has been made in improving the biological activity of MSCs by using physical, chemical and biological stimulation pretreatments, and hypoxia is one of the most widely used pretreatment methods. This article critically examines the impact and mechanisms of hypoxic preconditioning on various functions of MSCs such as proliferation, apoptosis, differentiation, homing, paracrine signaling, angiogenesis, and immune response.

Key words: Hypoxic preconditioning, Mesenchymal stem cells, HIF-1α
图1 缺氧预处理MSCs的功能及机制注：MSCs为间充质干细胞；EV为外泌体
表1 缺氧对MSCs分化的影响
MSCs来源 氧浓度 培养时间（d） 结果 机制
牙龈[28] 3% 2 神经元分化增加 诱导更多与神经元发育相关的基因表达
骨髓[29] 1% 1/3 神经胶质细胞分化增强 激活HIF-1α/VEGF通路
脂肪[30] 5% 14 平滑肌细胞分化增强 激活TGF-β/smad2通路
脐带[31] CoCl2 2 软骨分化增强 上调软骨分化调节基因SOX9表达
脂肪[32] 0.5% 2 软骨分化增强 抑制p38 MAPK通路
骨髓[33] CoCl2 4 成骨分化增强 激活OPG/ RANKL/RANK通路
骨髓[34] CoCl2 7 成骨分化增强 激活HIF-1α/ VEGF信号通路
骨髓[35] 2% 14 成骨分化减弱 下调成骨分化基因Runx2表达
牙周韧带[36] 3%+ CoCl2 3 成骨分化增强 激活HIF-1α/ VEGF/ Runx2通路
外周血[37,38] 1% 21 成骨分化减弱 上调了Notch-1表达
  9%   成骨分化增强 下调了Notch-1表达
睾丸[39] 5% 7 脂肪分化减弱 下调脂肪生成基因C/EBPα、PPARG表达
图2 MSCs沿着SDF-1、HGF浓度梯度在血管内迁移注：MSCs为间充质干细胞；SDF-1为基质细胞衍生因子-1；HGF为肝细胞生长因子
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