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中华肾病研究电子杂志 ›› 2024, Vol. 13 ›› Issue (02) : 87 -91. doi: 10.3877/cma.j.issn.2095-3216.2024.02.005

综述

间充质干细胞促进肾脏损伤修复机制研究进展
付章宁1, 耿晓东2, 张永军3, 陆宇平3, 孙冠南1, 张益帆1, 蔡广研4, 陈香美4, 洪权4,()   
  1. 1. 100853 北京,解放军医学院;100853 北京,解放军总医院第一医学中心肾脏病医学部、肾脏疾病国家重点实验室、国家慢性肾病临床医学研究中心、肾脏疾病研究北京市重点实验室
    2. 100853 北京,解放军总医院第一医学中心肾脏病医学部、肾脏疾病国家重点实验室、国家慢性肾病临床医学研究中心、肾脏疾病研究北京市重点实验室;100034 北京,中央军委机关事务管理总局服务局保健室
    3. 100034 北京,中央军委机关事务管理总局服务局保健室
    4. 100853 北京,解放军总医院第一医学中心肾脏病医学部、肾脏疾病国家重点实验室、国家慢性肾病临床医学研究中心、肾脏疾病研究北京市重点实验室
  • 收稿日期:2023-06-16 出版日期:2024-04-28
  • 通信作者: 洪权
  • 基金资助:
    国家重点研发计划项目(2018YFE0126600); 国家自然科学基金面上项目(82070741,82204744,82270758)

Research progress on the mechanism of mesenchymal stem cells in promoting renal injury repair

Zhangning Fu1, Xiaodong Geng2, Yongjun Zhang3, Yuping Lu3, Guannan Sun1, Yifan Zhang1, Guangyan Cai4, Xiangmei Chen4, Quan Hong4,()   

  1. 1. Chinese PLA Medical School, Beijing 100853; Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing 100853
    2. Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing 100853; Healthcare Office of Service Bureau, Agency for Offices Administration, Central Military Commission of People′s Republic of China, Beijing 100034; China
    3. Healthcare Office of Service Bureau, Agency for Offices Administration, Central Military Commission of People′s Republic of China, Beijing 100034; China
    4. Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing 100853
  • Received:2023-06-16 Published:2024-04-28
  • Corresponding author: Quan Hong
引用本文:

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]. 中华肾病研究电子杂志, 2024, 13(02): 87-91.

Zhangning Fu, Xiaodong Geng, Yongjun Zhang, Yuping Lu, Guannan Sun, Yifan Zhang, Guangyan Cai, Xiangmei Chen, Quan Hong. Research progress on the mechanism of mesenchymal stem cells in promoting renal injury repair[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(02): 87-91.

间充质干细胞具有强大的自我更新、多向分化和旁分泌能力,在肾脏疾病的治疗中展现出了良好的应用前景。本文综述了间充质干细胞在肾脏损伤修复中的作用机制,旨在为间充质干细胞的临床应用提供参考依据。

Mesenchymal stem cells (MSCs) are a kind of cells with robust self-renewal, multi-lineage differentiation, and paracrine potential, having a good application prospect in the treatment of renal diseases. This article reviewed the mechanism of MSCs in the repair of renal injury, aiming to provide reference for future clinical application of MSCs.

表1 在美国国立卫生研究院ClinicalTrials公共临床研究数据库注册并已完成的间充质干细胞治疗肾脏疾病的临床试验总结
[1]
Fraser SDS, Roderick PJ. Kidney disease in the global burden of disease study 2017 [J]. Nat Rev Nephrol, 2019, 15(4): 193-194.
[2]
Luyckx VA, Al-Aly Z, Bello AK, et al. Sustainable development goals relevant to kidney health: an update on progress [J]. Nat Rev Nephrol, 2021, 17(1): 15-32.
[3]
Kidney Disease: Improving Global Outcomes Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases [J]. Kidney Int, 2021, 100(4S): S1-S276.
[4]
Bochon B, Kozubska M, Surygala G et al. Mesenchymal stem cells-potential applications in kidney diseases [J]. Int J Mol Sci, 2019, 20(10): 2462.
[5]
Yun CW, Lee SH. Potential and therapeutic efficacy of cell-based therapy using mesenchymal stem cells for acute/chronic kidney disease [J]. Int J Mol Sci, 2019, 20(7): 1619.
[6]
Sears V, Ghosh G. Harnessing mesenchymal stem cell secretome: effect of extracellular matrices on proangiogenic signaling [J]. Biotechnol Bioeng, 2020, 117(4): 1159-1171.
[7]
Wu J, Huang L, He H, et al. Red cell distribution width to platelet ratio is associated with increasing in-hospital mortality in critically ill patients with acute kidney injury [J]. Dis Markers, 2022, 2022: 4802702.
[8]
Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo [J]. Exp Hematol, 2002, 30(1): 42-48.
[9]
Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli [J]. Blood, 2002, 99(10): 3838-3843.
[10]
Fazekas B, Griffin MD. Mesenchymal stromal cell-based therapies for acute kidney injury: progress in the last decade [J]. Kidney Int, 2020, 97(6): 1130-1140.
[11]
Hu CD, Kosaka Y, Marcus P, et al. Differential immunomodulatory effects of human bone marrow-derived mesenchymal stromal cells on natural killer cells [J]. Stem Cells Dev, 2019, 28(14): 933-943.
[12]
MarkovA, Thangavelu L, Aravindhan S, et al. Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders [J]. Stem Cell Res Ther, 2021, 12(1): 192.
[13]
Lopez-Garcia L, Castro-Manrreza ME. TNF-alpha and IFN-gamma participate in improving the immunoregulatory capacity of mesenchymal stem/stromal cells: importance of cell-cell contact and extracellular vesicles [J]. Int J Mol Sci, 2021, 22(17): 9531.
[14]
Fan L, Hu C, Chen J, et al. Interaction between mesenchymal stem cells and b-cells [J]. Int J Mol Sci, 2016, 17(5): 650.
[15]
Yuan Y, Li L, Zhu L, et al. Mesenchymal stem cells elicit macrophages into M2 phenotype via improving transcription factor EB-mediated autophagy to alleviate diabetic nephropathy [J]. Stem cells, 2020, 38(5): 639-652.
[16]
Chen J, Park HC, Addabbo F, et al. Kidney-derived mesenchymal stem cells contribute to vasculogenesis, angiogenesis and endothelial repair [J]. Kidney Int, 2008, 74(7): 879-889.
[17]
Meirelles Lda S, Fontes AM, Covas DT, et al. Mechanisms involved in the therapeutic properties of mesenchymal stem cells [J]. Cytokine Growth Factor Rev, 2009, 20(5-6): 419-427.
[18]
Pleniceanu O, Harari-Steinberg O, Omer D, et al. Successful introduction of human renovascular units into the mammalian kidney [J]. J Am Soc Nephrol, 2020, 31(12): 2757-2772.
[19]
Chen F, Chen N, Xia C, et al. Mesenchymal stem cell therapy in kidney diseases: potential and challenges [J]. Cell Transplant, 2023, 32: 9636897231164251.
[20]
Sano T, Nakajima T, Senda KA, et al. Image-based crosstalk analysis of cell-cell interactions during sprouting angiogenesis using blood-vessel-on-a-chip [J]. Stem Cell Res Ther, 2022, 13(1): 532.
[21]
Liang W, Chen X, Zhang S, et al. Mesenchymal stem cells as a double-edged sword in tumor growth: focusing on MSC-derived cytokines [J]. Cell Mol Biol Lett, 2021, 26(1): 3.
[22]
Katsuno T, Ozaki T, Saka Y, et al. Low serum cultured adipose tissue-derived stromal cells ameliorate acute kidney injury in rats [J]. Cell Transplant, 2013, 22(2): 287-297.
[23]
Li L, Cheng D, An X, et al. Mesenchymal stem cells transplantation attenuates hyperuricemic nephropathy in rats [J]. Int Immunopharmacol, 2021, 99: 108000.
[24]
Togel F, Weiss K, Yang Y, et al. Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury [J]. Am J Physiol Renal Physiol, 2007, 292(5): F1626-F1635.
[25]
Ni W, Fang Y, Xie L, et al. Adipose- derived mesenchymal stem cells transplantation alleviates renal injury in streptozotocin-induced diabetic nephropathy [J]. J Histochem Cytochem, 2015, 63(11): 842-853.
[26]
Meng XM, Nikolic-Paterson DJ, Lan HY. TGF-beta: the master regulator of fibrosis [J]. Nat Rev Nephrol, 2016, 12(6): 325-338.
[27]
Xiang E, Han B, Zhang Q, et al. Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis [J]. Stem Cell Res Ther, 2020, 11(1): 336.
[28]
Ishiuchi N, Nakashima A, Doi S, et al. Hypoxia-preconditioned mesenchymal stem cells prevent renal fibrosis and inflammation in ischemia-reperfusion rats [J]. Stem Cell Res Ther, 2020, 11(1): 130.
[29]
Ishiuchi N, Nakashima A, Doi S, et al. Serum-free medium and hypoxic preconditioning synergistically enhance the therapeutic effects of mesenchymal stem cells on experimental renal fibrosis [J]. Stem Cell Res Ther, 2021, 12(1): 472.
[30]
Wang B, Kim K, Tian M, et al. Engineered bone marrow stem cell-sheets alleviate renal damage in a rat chronic glomerulonephritis model [J]. Int J Mol Sci, 2023, 24(4): 3711.
[31]
Carlstrom M. Nitric oxide signalling in kidney regulation and cardiometabolic health [J]. Nat Rev Nephrol, 2021, 17(9): 575-590.
[32]
Braga PC, Alves MG, Rodrigues AS, et al. Mitochondrial pathophysiology on chronic kidney disease [J]. Int J Mol Sci, 2022, 23(3): 1776.
[33]
Stavely R, Nurgali K. The emerging antioxidant paradigm of mesenchymal stem cell therapy [J]. Stem Cells Transl Med, 2020, 9(9): 985-1006.
[34]
Liu B, Ding FX, Liu Y, et al. Human umbilical cord-derived mesenchymal stem cells conditioned medium attenuate interstitial fibrosis and stimulate the repair of tubular epithelial cells in an irreversible model of unilateral ureteral obstruction [J]. Nephrology (Carlton), 2018, 23(8): 728-736.
[35]
Savio-Silva C, Soinski-Sousa PE, Simplicio-Filho A, et al. Therapeutic potential of mesenchymal stem cells in a pre-Clinical model of diabetic kidney disease and obesity [J]. Int J Mol Sci, 2021, 22(4): 1546.
[36]
Hafazeh L, Changizi-Ashtiyani S, Ghasemi F, et al. Stem cell therapy ameliorates ischemia-reperfusion induced kidney injury after 24 hours reperfusion [J]. Iran J Kidney Dis, 2019, 13(6): 380-388.
[37]
Tang C, Livingston MJ, Liu Z, et al. Autophagy in kidney homeostasis and disease [J]. Nat Rev Nephrol, 2020, 16(9): 489-508.
[38]
刘华锋,杨俊伟. 细胞自噬与肾脏疾病研究中国专家共识[J]. 中国病理生理杂志2021, 37(10): 1876-1887.
[39]
Jia H, Yan Y, Liang Z, et al. Autophagy: a new treatment strategy for MSC-based therapy in acute kidney injury (Review) [J]. Mol Med Rep, 2018, 17(3): 3439-3447.
[40]
Ebrahim N, Ahmed IA, Hussien NI, et al. Mesenchymal stem cell-derived exosomes ameliorated diabetic nephropathy by autophagy induction through the mTOR signaling pathway [J]. Cells, 2018, 7(12): 226.
[41]
Huang J, Kong Y, Xie C, et al. Stem/progenitor cell in kidney: characteristics, homing, coordination, and maintenance [J]. Stem Cell Res Ther, 2021, 12(1): 197.
[42]
Birtwistle L, Chen XM, Pollock C. Mesenchymal stem cell-derived extracellular vesicles to the rescue of renal injury [J]. Int J Mol Sci, 2021, 22(12): 6596.
[43]
Harrell CR, Jovicic N, Djonov V, et al. Mesenchymal stem cell-derived exosomes and other extracellular vesicles as new remedies in the therapy of inflammatory diseases [J]. Cells, 2019, 8(12): 1605.
[44]
Liu H, Chen Y, Yin G, et al. Therapeutic prospects of microRNAs carried by mesenchymal stem cells-derived extracellular vesicles in autoimmune diseases [J]. Life Sci, 2021, 277: 119458.
[45]
Grange C, Skovronova R, Marabese F, et al. Stem cell-derived extracellular vesicles and kidney regeneration [J]. Cells, 2019, 8(10): 1240.
[46]
Eirin A, Lerman LO. Mesenchymal stem/stromal cell-derived extracellular vesicles for chronic kidney disease: are we there yet? [J]. Hypertension, 2021, 78(2): 261-269.
[47]
Lu Y, Wang L, Zhang M, et al. Mesenchymal stem cell-derived small extracellular vesicles: a novel approach for kidney disease treatment [J]. Int J Nanomedicine, 2022, 17: 3603-3618.
[48]
Ito T, Suzuki A, Okabe M, et al. Application of bone marrow-derived stem cells in experimental nephrology [J]. Exp Nephrol, 2001, 9(6): 444-450.
[49]
Wong CY, Cheong SK, Mok PL, et al. Differentiation of human mesenchymal stem cells into mesangial cells in post-glomerular injury murine model [J]. Pathology, 2008, 40(1): 52-57.
[50]
Masuya M, Drake CJ, Fleming PA, et al. Hematopoietic origin of glomerular mesangial cells [J]. Blood, 2003, 101(6): 2215-2218.
[51]
Morigi M, Imberti B, Zoja C, et al. Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure [J]. J Am Soc Nephrol, 2004, 15(7): 1794-1804.
[52]
Herrera MB, Bussolati B, Bruno S, et al. Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury [J]. Int J Mol Med, 2004, 14(6): 1035-1041.
[53]
Lin F, Cordes K, Li L, et al. Hematopoietic stem cells contribute to the regeneration of renal tubules after renal ischemia-reperfusion injury in mice [J]. J Am Soc Nephrol, 2003, 14(5): 1188-1199.
[54]
Yokoo T, Ohashi T, Shen JS, et al. Human mesenchymal stem cells in rodent whole-embryo culture are reprogrammed to contribute to kidney tissues [J]. Proc Natl Acad Sci USA, 2005, 102(9): 3296-3300.
[55]
Vassilopoulos G, Russell DW. Cell fusion: an alternative to stem cell plasticity and its therapeutic implications [J]. Curr Opin Genet Dev, 2003, 13(5): 480-485.
[56]
Brukman NG, Uygur B, Podbilewicz B, et al. How cells fuse [J]. J Cell Biol, 2019, 218(5): 1436-1451.
[57]
Held PK, Al-Dhalimy M, Willenbring H, et al. In vivo genetic selection of renal proximal tubules [J]. Mol Ther, 2006, 13(1): 49-58.
[58]
Swaminathan M, Stafford-Smith M, Chertow GM, et al. Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery [J]. J Am Soc Nephrol, 2018, 29(1): 260-267.
[59]
Makhlough A, Shekarchian S, Moghadasali R, et al. Bone marrow-mesenchymal stromal cell infusion in patients with chronic kidney disease: a safety study with 18 months of follow-up [J]. Cytotherapy, 2018, 20(5): 660-669.
[60]
Chun S, Choi CB, Kim MS, et al. Safety and tolerability of bone marrow-derived mesenchymal stem cells in lupus animal models and a phase I clinical trial in humans [J]. Lupus, 2022, 31(10): 1245-1253.
[61]
Liang J, Zhang H, Kong W, et al. Safety analysis in patients with autoimmune disease receiving allogeneic mesenchymal stem cells infusion: a long-term retrospective study [J]. Stem Cell Res Ther, 2018, 9(1): 312.
[62]
Makhlough A, Shekarchian S, Moghadasali R, et al. Safety and tolerability of autologous bone marrow mesenchymal stromal cells in ADPKD patients [J]. Stem Cell Res Ther, 2017, 8(1): 116.
[63]
Wang D, Li J, Zhang Y, et al. Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study [J]. Arthritis Res Ther, 2014, 16(2): R79.
[64]
Abumoawad A, Saad A, Ferguson CM, et al. In a Phase 1a escalating clinical trial, autologous mesenchymal stem cell infusion for renovascular disease increases blood flow and the glomerular filtration rate while reducing inflammatory biomarkers and blood pressure [J]. Kidney Int, 2020, 97(4): 793-804.
[65]
Deng D, Zhang P, Guo Y, et al. A randomised double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis [J]. Ann Rheum Dis, 2017, 76(8): 1436-1439.
[66]
Naeem A, Gupta N, Naeem U, et al. A comparison of isolation and culture protocols for human amniotic mesenchymal stem cells [J]. Cell Cycle, 2022, 21(15): 1543-1556.
[67]
Camilleri ET, Gustafson MP, Dudakovic A, et al. Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production [J]. Stem Cell Res Ther, 2016, 7(1): 107.
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