间充质干细胞在衰老相关疾病应用中的研究进展

doi:10.16352/j.issn.1001-6325.2023.01.0038

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (1): 38-45.doi: 10.16352/j.issn.1001-6325.2023.01.0038

• 特邀专题：成体干细胞基础创新与临床转化 • 上一篇下一篇

间充质干细胞在衰老相关疾病应用中的研究进展

商利鹏¹, 刘国祥², 丁晓燕¹, 李冰², 赵春华^1,3,4, 李霄霞^1,2*

青岛大学基础医学院 1. 干细胞再生医学研究院;2. 遗传学与细胞生物学系, 山东青岛 266071;
3.中国医学科学院北京协和医学院基础医学研究所组织工程中心,北京 100005;
4.上海大学生命科学学院细胞生物学系,上海 200444

收稿日期:2022-07-13 修回日期:2022-10-10 出版日期:2023-01-05 发布日期:2022-12-27
通讯作者: ^*lixiaoxia0805@163.com
基金资助:
国家重点研发计划青年项目(2018YFA0109800)

Research advances in application of mesenchymal stem cells for aging related diseases

SHANG Lipeng¹, LIU Guoxiang², DING Xiaoyan¹, LI Bing², ZHAO Chunhua^1,3,4, LI Xiaoxia^1,2*

1. Institute of Stem Cell and Regenerative Medicine; 2. Department of Genetics and Cell Biology, College of Basic Medicine, Qingdao University, Qingdao 266071;
3. Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005;
4. Department of Cell Biology, School of Life Sciences, Shanghai University, Shanghai 200444, China

Received:2022-07-13 Revised:2022-10-10 Online:2023-01-05 Published:2022-12-27
Contact: ^*lixiaoxia0805@163.com

摘要/Abstract

摘要： 衰老相关疾病严重影响老年人的身体健康,间充质干细胞(MSCs)在衰老相关疾病中的作用和机制研究受到越来越多的关注,国内外研究者也开展了多项相关的临床试验研究。本文对MSCs及其来源外泌体(exosome)在衰老相关的典型疾病如骨质疏松、帕金森病、2型糖尿病、动脉粥样硬化、慢性阻塞性肺病和肿瘤中的作用机制和临床试验进行综述,希望为MSCs在衰老相关疾病中的研究提供一定的理论依据和参考。

关键词: 间充质干细胞(MSCs), 衰老相关疾病, 外泌体

Abstract: Aging related diseases seriously affect the health of the elderly. Studies on the roles and mechanisms of mesenchymal stem cells (MSCs) in aging related diseases have attracted more and more attention. Besides, a number of relative clinical trials have been carried out in the domestic and overseas. This review summarizes the roles, molecular mechanisms, clinical trials of MSCs and MSCs-derived exosomes in several typical age-related diseases such as osteoporosis, Alzheimer's disease, Parkinson's disease, type 2 diabetes, atherosclerosis, chronic obstruc-tive pulmonary disease and tumor. This review may provide some theoretical reference and advices for future studies of MSCs in aging related diseases.

Key words: mesenchymal stem cells(MSCs), aging related diseases, exosome

中图分类号:

R329.28

商利鹏, 刘国祥, 丁晓燕, 李冰, 赵春华, 李霄霞. 间充质干细胞在衰老相关疾病应用中的研究进展[J]. 基础医学与临床, 2023, 43(1): 38-45.

SHANG Lipeng, LIU Guoxiang, DING Xiaoyan, LI Bing, ZHAO Chunhua, LI Xiaoxia. Research advances in application of mesenchymal stem cells for aging related diseases[J]. Basic & Clinical Medicine, 2023, 43(1): 38-45.

参考文献 42

[1]	Wyss-Coray T. Ageing, neurodegeneration and brain rejuvenation[J]. Nature, 2016, 539:180-186.
[2]	Lopez-Otin C, Blasco MA, Partridge L, et al. The hallmarks of aging[J]. Cell, 2013, 153:1194-1217.
[3]	Krampera M, Le Blanc K. Mesenchymal stromal cells: Putative microenvironmental modulators become cell therapy[J]. Cell Stem Cell, 2021, 28:1708-1725.
[4]	Han Y, Yang J, Fang J, et al. The secretion profile of mesenchymal stem cells and potential applications in treating human diseases[J]. Signal Transduct Target Ther, 2022, 7:92-110.
[5]	Piffoux M, Volatron J, Cherukula K,et al. Engineering and loading therapeutic extracellular vesicles for clinical translation: A data reporting frame for comparability[J]. Adv Drug Deliv Rev, 2021, 178:113972-113980.
[6]	Staff NP, Jones DT, Singer W. Mesenchymal stromal cell therapies for neurodegenerative diseases[J]. Mayo Clin Proc, 2019, 94:892-905.
[7]	Malekpour K, Hazrati A, Zahar M, et al. The potential use of mesenchymal stem cells and their derived exosomes for orthopedic diseases treatment[J]. Stem Cell Rev Rep, 2022, 18:933-951.
[8]	Sun Y, Shi H, Yin S, et al. Human mesenchymal stem cell derived exosomes alleviate type 2 diabetes mellitus by reversing peripheral insulin resistance and relieving beta-cell destruction[J]. ACS Nano, 2018, 12:7613-7628.
[9]	Arthur A, Gronthos S. Clinical application of bone marrow mesenchymal stem/stromal cells to repair skeletal tissue[J]. Int J of Mol Sci, 2020, 21:9759-9786.
[10]	Jiang Y, Zhang P, Zhang X, et al. Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis[J]. Cell Prolif, 2021, 54:12956-12975.
[11]	Li H, Fan J, Fan L, et al. MiRNA-10b reciprocally stimulates osteogenesis and inhibits adipogenesis partly through the TGF-beta/SMAD2 signaling pathway[J]. Aging Dis, 2018, 9:1058-1073.
[12]	Fricova D, Korchak JA, Zubair AC. Challenges and translational considerations of mesenchymal stem/stromal cell therapy for Parkinson's disease[J]. NPJ Regen Med, 2020, 5:20-29.
[13]	Chen HX, Liang FC, Gu P, et al. Exosomes derived from mesenchymal stem cells repair a Parkinson's disease model by inducing autophagy[J]. Cell Death Dis, 2020, 11:288-304.
[14]	Xue C, Li X, Ba L et al. MSCs-derived exosomes can enhance the angiogenesis of human brain MECs and show therapeutic potential in a mouse model of parkinson's disease[J]. Aging Dis, 2021, 12:1211-1222.
[15]	Park KS, Bandeira E, Shelke GV, et al. Enhancement of therapeutic potential of mesenchymal stem cell-derived extracellular vesicles[J]. Stem Cell Res Ther, 2019, 10:288-302.
[16]	Si Y, Zhao Y, Hao H, et al. Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic rats: identification of a novel role in improving insulin sensitivity[J]. Diabetes, 2012, 61:1616-1625.
[17]	Li H, Zhu H, Ge T, et al. Mesenchymal stem cell-based therapy for diabetes mellitus: enhancement strategies and future perspectives[J]. Stem Cell Rev Reports, 2021, 17:1552-1569.
[18]	Zhang Y, Chen W, Feng B, et al. The clinical efficacy and safety of stem cell therapy for diabetes mellitus: a systematic review and meta-analysis[J]. Aging Dis, 2020, 11:141-153.
[19]	Lin Y, Zhu W, Chen X. The involving progress of MSCs based therapy in atherosclerosis[J]. Stem Cell Res Ther, 2020, 11:216-228.
[20]	林颖, 胡豪畅, 成绩, 等. 间充质干细胞治疗动脉粥样硬化的研究进展[J]. 中华心血管病杂志, 2021, 49:288-292.doi: 10.3760/cma.j.cn112148-20210129-00106.
[21]	Rahmani A, Saleki K, Javanmehr N, et al. Mesenchymal stem cell-derived extracellular vesicle-based therapies protect against coupled degeneration of the central nervous and vascular systems in stroke[J]. Ageing Res Rev, 2020, 62:101106-101126.
[22]	Takafuji Y, Hori M, Mizuno T, et al. Humoral factors secreted from adipose tissue-derived mesenchymal stem cells ameliorate atherosclerosis in Ldlr-/- mice[J]. Cardiovasc Res, 2019, 115:1041-1051.
[23]	Xiao X, Xu M, Yu H, et al. Mesenchymal stem cell-derived small extracellular vesicles mitigate oxidative stress-induced senescence in endothelial cells via regulation of miR-146a/Src[J]. Signal Transduct Target Ther, 2021, 6:354-368.
[24]	Ma J, Chen L, Zhu X, et al. Mesenchymal stem cell-derived exosomal miR-21a-5p promotes M2 macrophage polarization and reduces macrophage infiltration to attenuate atherosclerosis[J]. Acta Biochim Biophys Sin(Shanghai), 2021, 53:1227-1236.
[25]	Li J, Xue H, Li T, et al. Exosomes derived from mesenchymal stem cells attenuate the progression of atherosclerosis in ApoE(-/-) mice via miR-let7 mediated infiltration and polarization of M2 macrophage[J]. Biochem Biophys Res Commun, 2019, 510:565-572.
[26]	Chen YT, Miao K, Zhou L, et al. Stem cell therapy for chronic obstructive pulmonary disease[J]. Chin Med J (Engl), 2021, 134:1535-1545.
[27]	Abbaszadeh H, Ghorbani F, Abbaspour-Aghdam S, et al. Chronic obstructive pulmonary disease and asthma: mesenchymal stem cells and their extracellular vesicles as potential therapeutic tools[J]. Stem Cell Res Ther, 2022, 13:262-276.
[28]	Harrell CR, Miloradovic D, Sadikot R, et al. Molecular and cellular mechanisms responsible for beneficial effects of mesenchymal stem cell-derived product “Exo-d-MAPPS” in attenuation of chronic airway inflammation[J]. Anal Cell Pathol (Amst), 2020, 2020:3153891-3153905.
[29]	Cruz FF, Rocco PRM. The potential of mesenchymal stem cell therapy for chronic lung disease[J]. Expert Rev Respir Med, 2020, 14:31-39.
[30]	Squassoni SD, Sekiya EJ, Fiss E,et al. Autologous infusion of bone marrow and mesenchymal stromal cells in patients with chronic obstructive pulmonary disease: phase i randomized clinical trial[J]. Int J Chron Obstruct Pulmon Dis, 2021, 16:3561-3574.
[31]	Yin W, Wang J, Jiang L, et al. Cancer and stem cells[J]. Exp Biol Med (Maywood), 2021, 246:1791-1801.
[32]	Hanahan D. Hallmarks of cancer: new dimensions[J]. Cancer Discov, 2022, 12:31-46.
[33]	Shi Y, Du L, Lin L, et al. Tumour-associated mesenchymal stem/stromal cells: emerging therapeutic targets[J]. Nat Rev Drug Discov, 2017, 16:35-52.
[34]	Timaner M, Tsai KK, Shaked Y. The multifaceted role of mesenchymal stem cells in cancer[J]. Semin Cancer Biol, 2020, 60:225-237.
[35]	Lu L, Chen G, Yang J, et al. Bone marrow mesenchymal stem cells suppress growth and promote the apoptosis of glioma U251 cells through downregulation of the PI3K/AKT signaling pathway[J]. Biomed Pharmacother, 2019, 112-108625-108638.
[36]	Hughes RM, Simons BW, Khan H,et al. Asporin restricts mesenchymal stromal cell differentiation, alters the tumor microenvironment, and drives metastatic progression[J]. Cancer Res, 2019, 79:3636-3650.
[37]	Lan T, Luo M, Wei X. Mesenchymal stem/stromal cells in cancer therapy[J]. J Hematol Oncol, 2021, 14:195-210.
[38]	Li X, Sun Z, Peng G,et al. Single-cell RNA sequencing reveals a pro-invasive cancer-associated fibroblast sub-group associated with poor clinical outcomes in patients with gastric cancer[J]. Theranostics, 2022, 12:620-638.
[39]	Takayama Y, Kusamori K, Nishikawa M. Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics[J]. Expert Opin Drug Deliv, 2021, 18:1627-1642.
[40]	Whiteside TL. Exosome and mesenchymal stem cell cross-talk in the tumor microenvironment[J]. Semin Immunol, 2018, 35:69-79.
[41]	Madl CM, Heilshorn SC, Blau HM. Bioengineering strategies to accelerate stem cell therapeutics[J]. Nature, 2018, 557:335-342.
[42]	Shi Y, Wang Y, Li Q, et al. Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases[J]. Nat Rev Nephrol, 2018, 14:493-507.

间充质干细胞在衰老相关疾病应用中的研究进展

Research advances in application of mesenchymal stem cells for aging related diseases

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 42

相关文章 15

编辑推荐

Metrics

本文评价

[1]	于曼殊, 赵晓敏, 邱明月, 刘春冉, 那日苏. 牙源性干细胞治疗帕金森病的研究进展[J]. 基础医学与临床, 2024, 44(9): 1298-1302.
[2]	赵俊丽, 朱君君, 詹秋楠, 刘苗. 骨髓间充质干细胞来源外泌体抑制高糖诱导的腹膜间皮细胞EMT[J]. 基础医学与临床, 2024, 44(8): 1149-1156.
[3]	高璐, 蔡孟华, 许依, 何维, 陈慧, 张建民. 过表达膜定位IL-3的293T细胞外泌体的纯化及体外功能验证[J]. 基础医学与临床, 2024, 44(7): 947-953.
[4]	龚金涛, 厉建伟, 李玉恒, 李堑, 赵春华. 骨髓间充质干细胞缓解模拟微重力对小鼠大脑皮质的不利影响[J]. 基础医学与临床, 2024, 44(6): 772-778.
[5]	颜晨红, 金儿. 外泌体PD-L1在非小细胞肺癌诊断和治疗上的研究进展[J]. 基础医学与临床, 2023, 43(9): 1457-1461.
[6]	方路, 刘睿奇, 梁鹏, 岑瑛. 外泌体miRNAs在器官纤维化中作用的研究进展[J]. 基础医学与临床, 2023, 43(9): 1472-1476.
[7]	杨雅倩, 潘艳芳, 屈梦扬, 方艳, 应小平, 张玫倩, 魏静. 外泌体在肝癌前病变发生发展中作用的研究进展[J]. 基础医学与临床, 2023, 43(9): 1453-1456.
[8]	陈星星, 赛依帕, 胡筱霞, 王三萍, 罗璇, 刘璟. 人脐带间充质干细胞来源外泌体对脑瘫小鼠神经功能损伤的保护作用[J]. 基础医学与临床, 2023, 43(8): 1201-1207.
[9]	闫霖, 陆珏秀, 罗颖, 刘先霞. BM-MSCs来源外泌体介导铁死亡减轻大鼠心肌细胞系H9c2缺氧/复氧损伤[J]. 基础医学与临床, 2023, 43(5): 771-776.
[10]	崔诗雨, 张海峰. 外泌体在新型冠状病毒感染和传播中作用的研究进展[J]. 基础医学与临床, 2023, 43(4): 680-684.
[11]	姚刘旭, 李玉红, 蒋宗明. 外泌体lncRNA在结直肠癌液体活检中的研究进展[J]. 基础医学与临床, 2023, 43(2): 317-321.
[12]	姜俣, 钱海燕. 间充质干细胞治疗心肌梗死的研究进展[J]. 基础医学与临床, 2023, 43(1): 21-29.
[13]	汪海燕, 韩钦, 赵春华. 间充质干细胞的免疫调节可塑性及其临床应用策略[J]. 基础医学与临床, 2023, 43(1): 2-11.
[14]	陈莉莉, 孙永红, 雷晓燕, 王建军, 陈星星, 鲍柏辛. 间充质干细胞外泌体治疗肺部疾病的研究进展[J]. 基础医学与临床, 2023, 43(1): 192-195.
[15]	李英杰, 杨庭楷, 纪志刚, 文进. 外泌体在前列腺癌诊疗中的研究进展[J]. 基础医学与临床, 2022, 42(1): 163-167.