切换至 "中华医学电子期刊资源库"

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
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/OL]. 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/OL]. 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。

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.

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
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
1
刘艳妮, 倪敏, 张睿, 等. 脂肪干细胞治疗复杂性肛瘘:作用与机制[J]. 中国组织工程研究, 2018, 22(33):5399-5407.
2
Li Y, Wang F, Liang H, et al. Efficacy of mesenchymal stem cell transplantation therapy for type 1 and type 2 diabetes mellitus: a meta-analysis[J]. Stem Cell Res Ther, 2021, 12(1):273.doi: 10.1186/s13287-021-02342-5.
3
张琪,倪敏,刘艳妮,等.间充质干细胞治疗炎症性肠病机制[J]. 现代中西医结合杂志, 2020, 29(19):2154-2158.
4
李佩霖,朱恒.间充质干细胞生物学特性的可塑性研究进展[J].中国实验血液学杂志, 2021, 29(2):629-632.
5
Kim H, Kwon S. Dual effects of hypoxia on proliferation and osteogenic differentiation of mouse clonal mesenchymal stem cells[J]. Bioprocess Biosyst Eng, 2021, 44(9):1831-1839.
6
Konjar S, Pavsic M, Veldhoen M. Regulation of oxygen homeostasis at the intestinal epithelial barrier site[J]. Int J Mol Sci, 2021, 22(17):9170.doi: 10.3390/ijms22179170.
7
Ortiz-Prado E, Dunn JF, Vasconez J, et al. Partial pressure of oxygen in the human body: a general review[J]. Am J Blood Res, 2019, 9(1):1-14.
8
Samal JRK, Rangasami VK, Samanta S, et al. Discrepancies on the role of oxygen gradient and culture condition on mesenchymal stem cell fate[J]. Adv Healthc Mater, 2021, 10(6):e2002058. doi: 10.1002/adhm.202002058.
9
Sekhon MS, Ainslie PN, Menon DK, et al. Brain hypoxia secondary to diffusion limitation in hypoxic ischemic brain injury postcardiac arrest[J]. Crit Care Med, 2020, 48(3):378-384.
10
Denu RA, Hematti P. Optimization of oxidative stress for mesenchymal stromal/stem cell engraftment, function and longevity[J]. Free Radic Biol Med, 2021, 167:193-200.
11
Moriyama H, Moriyama M, Ozawa T, et al. Notch signaling enhances stemness by regulating metabolic pathways through modifying p53, NF-kappaB, and HIF-1alpha[J]. Stem Cells Dev, 2018, 27(13):935-947.
12
Kim H, Kwon S. Dual effects of hypoxia on proliferation and osteogenic differentiation of mouse clonal mesenchymal stem cells[J]. Bioprocess Biosyst Eng, 2021, 44(9):1831-1839.
13
Lee J, Kim HS, Kim SM, et al. Hypoxia upregulates mitotic cyclins which contribute to the multipotency of human mesenchymal stem cells by expanding proliferation lifespan[J]. Mol Cells, 2018, 41(3):207-213.
14
Choi JR, Yong KW, Wan Safwani WKZ. Effect of hypoxia on human adipose-derived mesenchymal stem cells and its potential clinical applications[J]. Cell Mol Life Sci, 2017, 74(14):2587-2600.
15
刘毓斌,胡雪峰.糖原合酶激酶-3β在肿瘤细胞中的分子作用机制[J]. 中国生物化学与分子生物学报, 2020, 36(3):259-266.
16
Bétous R, Renoud ML, Hoede C, et al. Human adipose-derived stem cells expanded under ambient oxygen concentration accumulate oxidative DNA lesions and experience procarcinogenic DNA replication stress[J]. Stem Cells Transl Med, 2017, 6(1):68-76.
17
Tsai CC, Chen YJ, Yew TL, et al. Hypoxia inhibits senescence and maintains mesenchymal stem cell properties through down-regulation of E2A-p21 by HIF-TWIST[J]. Blood, 2011, 117(2):459-469.
18
Zhang J, Xiong L, Tang W, et al. Hypoxic culture enhances the expansion of rat bone marrow-derived mesenchymal stem cells via the regulatory pathways of cell division and apoptosis[J]. In Vitro Cell Dev Biol Anim, 2018, 54(9):666-676.
19
张优,严卫亚,沈振亚,等.低氧预处理诱导骨髓间充质干细胞Pim-1激酶高表达抑制细胞凋亡[J]. 中国组织工程研究, 2016, 20(14):1989-1998.
20
Zhang Y, Lei W, Yan W, et al. microRNA-206 is involved in survival of hypoxia preconditioned mesenchymal stem cells through targeting Pim-1 kinase[J]. Stem Cell Res Ther, 2016, 7(1):61.
21
Lee JH, Yoon YM, Lee SH. Hypoxic preconditioning promotes the bioactivities of mesenchymal stem cells via the HIF-1α-GRP78-Akt Axis[J]. Int J Mol Sci, 2017, 18(6):1320. doi:10.3390/ijms18061320.
22
Ibrahim IM, Abdelmalek DH, Elfiky AA. GRP78: A cell's response to stress[J]. Life Sci, 2019, 226:156-163.
23
Xu L, Liu Y, Sun Y, et al. Tissue source determines the differentiation potentials of mesenchymal stem cells: a comparative study of human mesenchymal stem cells from bone marrow and adipose tissue[J]. Stem Cell Res Ther, 2017, 8(1):275.doi: 10.1186/s13287-017-0716-x.
24
Lee SM, Jun DW, Kang HT, et al. Optimal hypoxic preconditioning of human embryonic stem cell-derived mesenchymal stem cells (hES-MSCs) and their characteristics[J]. Int J Stem Cells, 2021, 14(2):221-228.
25
Islam MR, Liu S, Wang X, et al. Deep learning for misinformation detection on online social networks: a survey and new perspectives[J]. Soc Netw Anal Min, 2020, 10(1):82.doi: 10.1007/s13278-020-00696-x.
26
Costa LA, Eiro N, Fraile M, et al. Functional heterogeneity of mesenchymal stem cells from natural niches to culture conditions: implications for further clinical uses[J]. Cell Mol Life Sci, 2021, 78(2):447-467.
27
Zhang Y, Hao Z, Wang P, et al. Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1alpha-mediated promotion of angiogenesis in a rat model of stabilized fracture[J]. Cell Prolif, 2019, 52(2):e12570.doi: 10.1111/cpr.12570.
28
Gugliandolo A, Diomede F, Scionti D, et al. The role of hypoxia on the neuronal differentiation of gingival mesenchymal stem cells: a transcriptional study[J]. Cell Transplant, 2019, 28(5):538-552.
29
Yuan X, Luo Q, Shen L, et al. Hypoxic preconditioning enhances the differentiation of bone marrow stromal cells into mature oligodendrocytes via the mTOR/HIF-1alpha/VEGF pathway in traumatic brain injury[J]. Brain Behav, 2020, 10(7):e1675.doi: 10.1002/brb3.1675.
30
Wang F, Zachar V, Pennisi C-P, et al. Hypoxia enhances differentiation of adipose tissue-derived stem cells toward the smooth muscle phenotype[J]. Int J Mol Sci, 2018, 19(2):517. doi:10.3390/ijms19020517.
31
Teti G, Focaroli S, Salvatore V, et al. The hypoxia-mimetic agent cobalt chloride differently affects human mesenchymal stem cells in their chondrogenic potential[J]. Stem Cells Int, 2018, 2018:3237253.doi: 10.1155/2018/3237253.
32
Govoni M, Muscari C, Bonafè F, et al. A brief very-low oxygen tension regimen is sufficient for the early chondrogenic commitment of human adipose-derived mesenchymal stem cells[J]. Adv Med Sci, 2021, 66(1):98-104.
33
史新连, 胡碧波, 任曼曼, 喻文彬, 邓辉. 低氧调控大鼠骨髓间充质干细胞OPG/RANKL mRNA的表达[J]. 上海口腔医学, 2017, 26(3): 258-262.
34
Yu X, Wan Q, Ye X, et al. Cellular hypoxia promotes osteogenic differentiation of mesenchymal stem cells and bone defect healing via STAT3 signaling[J]. Cell Mol Biol Lett, 2019, 24:64.doi: 10.1186/s11658-019-0191-8.
35
Zhang P, Ha N, Dai Q, et al. Hypoxia suppresses osteogenesis of bone mesenchymal stem cells via the extracellular signal regulated 1/2 and p38mitogen activated protein kinase signaling pathways[J]. Mol Med Rep, 2017, 16(4):5515-5522.
36
Xu Q, Liu Z, Guo L, et al. Hypoxia mediates runt-related transcription factor 2 expression via induction of vascular endothelial growth factor in periodontal ligament stem cells[J]. Mol Cells, 2019, 42(11):763-772.
37
Yang M, Liu H, Wang Y, et al. Hypoxia reduces the osteogenic differentiation of peripheral blood mesenchymal stem cells by upregulating Notch-1 expression[J]. Connect Tissue Res, 2019, 60(6):583-596.
38
Lee SY, Long F. Notch signaling suppresses glucose metabolism in mesenchymal progenitors to restrict osteoblast differentiation[J]. J Clin Invest, 2018, 128(12):5573-5586.
39
Singh SP, Kharche SD, Pathak M, et al. Low oxygen tension potentiates proliferation and stemness but not multilineage differentiation of caprine male germline stem cells[J]. Mol Biol Rep, 2021, 48(6):5063-5074.
40
刘远志,周吉银,黄毅岚,等.促进间充质干细胞归巢的研究进展及其相关机制[J].生理科学进展, 2018, 49(3):237-241.
41
刘想忠,李章华,许海甲. SDF-1促进BMSCs迁移的研究进展[J]. 中国骨质疏松杂志, 2019, 25(3):408-415.
42
Obradovic H, Krstic J, Trivanovic D, et al. Improving stemness and functional features of mesenchymal stem cells from Wharton's jelly of a human umbilical cord by mimicking the native, low oxygen stem cell niche[J]. Placenta, 2019, 82:25-34.
43
Yu X, Wan Q, Cheng G, et al. CoCl2, a mimic of hypoxia, enhances bone marrow mesenchymal stem cells migration and osteogenic differentiation via STAT3 signaling pathway[J]. Cell Biol Int, 2018, 42(10):1321-1329.
44
Li L, Jaiswal PK, Makhoul G, et al. Hypoxia modulates cell migration and proliferation in placenta-derived mesenchymal stem cells[J]. J Thorac Cardiovasc Surg, 2017, 154(2):543-552.e3.
45
Ciria M, García NA, Ontoria-Oviedo I, et al. Mesenchymal stem cell migration and proliferation are mediated by hypoxia-inducible factor-1alpha upstream of notch and SUMO pathways[J]. Stem Cells Dev, 2017, 26(13):973-985.
46
Rosová I, Dao M, Capoccia B, et al. Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells[J]. Stem Cells, 2008, 26(8):2173-2182.
47
Choi JH, Lee YB, Jung J, et al. Hypoxia inducible factor-1alpha regulates the migration of bone marrow mesenchymal stem cells via integrin alpha 4[J]. Stem Cells Int, 2016, 2016:7932185.doi: 10.1155/2016/7932185.
48
Shao H, Im H, Castro CM, et al. New technologies for analysis of extracellular vesicles[J]. Chem Rev, 2018, 118(4):1917-1950.
49
Han Y, Ren J, Bai Y, et al. Exosomes from hypoxia-treated human adipose-derived mesenchymal stem cells enhance angiogenesis through VEGF/VEGF-R[J]. Int J Biochem Cell Biol, 2019, 109:59-68.
50
Gómez-Ferrer M, Villanueva-Badenas E, Sánchez-Sánchez R, et al. HIF-1α and pro-inflammatory signaling improves the immunomodulatory activity of MSC-derived extracellular vesicles[J]. Int J Mol Sci, 2021, 22(7):3416. doi: 10.3390/ijms22073416.
51
Dong L, Wang Y, Zheng T, et al. Hypoxic hUCMSC-derived extracellular vesicles attenuate allergic airway inflammation and airway remodeling in chronic asthma mice[J]. Stem Cell Res Ther, 2021, 12(1):4. doi: 10.1186/s13287-020-02072-0.
52
Gupta S, Rawat S, Krishnakumar V, et al. Hypoxia preconditioning elicit differential response in tissue-specific MSCs via immunomodulation and exosomal secretion[J]. Cell Tissue Res, 2022, 388(3):535-548.
53
Huang T, Jia Z, Fang L, et al. Extracellular vesicle-derived miR-511-3p from hypoxia preconditioned adipose mesenchymal stem cells ameliorates spinal cord injury through the TRAF6/S1P axis[J]. Brain Res Bull, 2022, 180:73-85.
54
Ge L, Xun C, Li W, et al. Extracellular vesicles derived from hypoxia-preconditioned olfactory mucosa mesenchymal stem cells enhance angiogenesis via miR-612[J]. J Nanobiotechnology, 2021, 19(1):380.doi: 10.1186/s12951-021-01126-6.
55
Kojima Y, Tsuchiya A, Ogawa M, et al. Mesenchymal stem cells cultured under hypoxic conditions had a greater therapeutic effect on mice with liver cirrhosis compared to those cultured under normal oxygen conditions[J]. Regen Ther, 2019, 11:269-281.
56
胡继宏,贾佳,路娟,等.低氧下血管内皮细胞生长因子转染人骨髓间充质干细胞向血管内皮样细胞的分化[J]. 中国组织工程研究, 2017, 21(9):1352-1356.
57
侯婧瑛,郭天柱,于萌蕾,等. 缺氧预处理通过激活MALAT1靶向抑制miR-195促进骨髓间充质干细胞的生存和血管形成[J]. 中国组织工程研究, 2022, 26(7):1005-1011.
58
Li Q, Xu Y, Lv K, et al. Small extracellular vesicles containing miR-486-5p promote angiogenesis after myocardial infarction in mice and nonhuman primates[J]. Sci Transl Med, 2021, 13(584):eabb0202. doi: 10.1126/scitranslmed.abb0202.
59
Xue C, Shen Y, Li X, et al. Exosomes derived from hypoxia-treated human adipose mesenchymal stem cells enhance angiogenesis through the PKA signaling pathway[J]. Stem Cells Dev, 2018, 27(7):456-465.
60
Contreras-Lopez R, Elizondo-Vega R, Paredes MJ, et al. HIF1α-dependent metabolic reprogramming governs mesenchymal stem/stromal cell immunoregulatory functions[J]. FASEB J, 2020, 34(6): 8250-8264.
61
Liu W, Rong Y, Wang J, et al. Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization[J]. J Neuroinflammation, 2020, 17(1):47.doi: 10.1186/s12974-020-1726-7.
62
Kim R, Song B-W, Kim M, et al. Regulation of alternative macrophage activation by MSCs derived hypoxic conditioned medium, via the TGF-beta1/Smad3 pathway[J]. BMB Rep, 2020, 53(11):600-604.
63
Zhang X, Xu Y, Liu H, et al. HIF-2α-ILK is involved in mesenchymal stromal cell angiogenesis in multiple myeloma under hypoxic conditions[J]. Technol Cancer Res Treat, 2018, 17:1533033818764473. doi: 10.1177/1533033818764473.
[1] 曹胜军, 李全, 符雪, 邵天喜, 周延华. 人脂肪间充质干细胞多层膜片对促进裸鼠皮肤缺损愈合的效果观察[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(04): 341-347.
[2] 傅红兴, 王植楷, 谢贵林, 蔡娟娟, 杨威, 严盛. 间充质干细胞促进胰岛移植效果的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 351-360.
[3] 王大伟, 陆雅斐, 皇甫少华, 陈玉婷, 陈澳, 江滨. 间充质干细胞通过调控免疫机制促进创面愈合的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 361-366.
[4] 袁园园, 岳乐淇, 张华兴, 武艳, 李全海. 间充质干细胞在呼吸系统疾病模型中肺组织分布及治疗机制的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 374-381.
[5] 王俊楠, 刘晔, 李若涵, 叶青松. 间充质干细胞调控肠脑轴治疗神经系统疾病的潜力[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(05): 313-319.
[6] 孙海燕, 周士燕, 张杉杉, 张研, 张茜. 间充质干细胞及其外泌体在高原肺水肿中的潜在治疗机制研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(03): 186-190.
[7] 杨阳, 王琤, 周文土, 周冰. Caveolae/Caveolin-1与膜胆固醇共同调控小鼠BMSCs成骨分化[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(03): 137-142.
[8] 陈俊秋, 邬绿莹, 马予洁, 林娜, 刘飞, 陈津. 基于lncRNA微阵列芯片技术探索间充质干细胞外泌体增强小鼠胰岛β细胞抗低氧损伤的潜在机制[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(03): 129-136.
[9] 凌淑洵, 涂玥, 刘思逸. 间充质干细胞在慢性肾脏病研究领域现状和趋势的知识图谱可视化分析[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(02): 73-82.
[10] 王娟, 刘晔, 熊威, 蒋财磊, 贺燕, 叶青松. 间充质干细胞缓解阿尔茨海默病氧化应激的新思路[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(02): 93-106.
[11] 梁国豪, 张茜, 张研. 间充质干细胞及其衍生物治疗高原低氧环境下心血管疾病的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(02): 107-112.
[12] 陆雅斐, 皇甫少华, 马传学, 江滨. 间充质干细胞治疗肛瘘手术方式的研究进展[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(03): 242-249.
[13] 史敬萱, 焦圆圆, 田景玮, 卓莉. 间充质干细胞来源外泌体治疗动物糖尿病肾脏病的效果:Meta分析[J/OL]. 中华肾病研究电子杂志, 2024, 13(02): 79-86.
[14] 付章宁, 耿晓东, 张永军, 陆宇平, 孙冠南, 张益帆, 蔡广研, 陈香美, 洪权. 间充质干细胞促进肾脏损伤修复机制研究进展[J/OL]. 中华肾病研究电子杂志, 2024, 13(02): 87-91.
[15] 汪鹏飞, 程莹莹, 赵海康. 骨髓间充质干细胞改善神经病理性疼痛的机制探讨[J/OL]. 中华脑科疾病与康复杂志(电子版), 2024, 14(04): 230-234.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?