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间充质基质细胞治疗实体器官移植。

Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation.

机构信息

Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Aldo & Cele Daccò Clinical Research Center for Rare Diseases, Bergamo, Italy.

出版信息

Front Immunol. 2021 Feb 10;11:618243. doi: 10.3389/fimmu.2020.618243. eCollection 2020.

DOI:10.3389/fimmu.2020.618243
PMID:33643298
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7902912/
Abstract

Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft function without the need for immunosuppression, is considered the Holy Grail of the field of solid organ transplantation. However, spontaneous tolerance in solid allograft recipients is a rare and unpredictable event. Several strategies that include peri-transplant administration of non-hematopoietic immunomodulatory cells can safely and effectively induce tolerance in pre-clinical models of solid organ transplantation. Mesenchymal stromal cells (MSC), non-hematopoietic cells that can be obtained from several adult and fetal tissues, are among the most promising candidates. In this review, we will focus on current pre-clinical evidence of the immunomodulatory effect of MSC in solid organ transplantation, and discuss the available evidence of their safety and efficacy in clinical trials.

摘要

移植是治疗多种实体器官衰竭的金标准治疗方法,包括肾脏、肝脏、心脏、肺和小肠。定制免疫抑制剂的使用在移植后早期显著提高了移植物和患者的存活率,但由于慢性移植物排斥的发展,长期结果常常不尽如人意,最终导致移植失败。此外,长期免疫抑制会产生严重的副作用,严重影响患者的生存和生活质量。实现耐受,即无需免疫抑制即可稳定的移植物功能,被认为是实体器官移植领域的圣杯。然而,实体同种异体移植物受者中的自发耐受是一种罕见且不可预测的事件。几种策略,包括移植前给予非造血免疫调节细胞,可以在实体器官移植的临床前模型中安全有效地诱导耐受。间充质基质细胞(MSC)是一种可以从几种成人和胎儿组织中获得的非造血细胞,是最有前途的候选者之一。在这篇综述中,我们将重点介绍 MSC 在实体器官移植中的免疫调节作用的当前临床前证据,并讨论其在临床试验中的安全性和有效性的现有证据。

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Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation.间充质基质细胞治疗实体器官移植。
Front Immunol. 2021 Feb 10;11:618243. doi: 10.3389/fimmu.2020.618243. eCollection 2020.
2
Mesenchymal stromal cells to promote solid organ transplantation tolerance.间充质基质细胞促进实体器官移植耐受。
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Mesenchymal stromal cells for tolerance induction in organ transplantation.用于器官移植中诱导免疫耐受的间充质基质细胞
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Mesenchymal Stromal Cells in Solid Organ Transplantation.实体器官移植中的间充质基质细胞。
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J Hepatol. 2017 Jul;67(1):47-55. doi: 10.1016/j.jhep.2017.03.001. Epub 2017 Mar 9.

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Advances in Regulatory Cell Therapy for Type 1 Diabetes: Emerging Strategies and Future Directions.1型糖尿病调节性细胞疗法的进展:新兴策略与未来方向
Eur J Immunol. 2025 May;55(5):e202451722. doi: 10.1002/eji.202451722.
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Regulatory Immune Cell-derived Exosomes: Modes of Action and Therapeutic Potential in Transplantation.调节性免疫细胞衍生的外泌体:移植中的作用模式及治疗潜力

本文引用的文献

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Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors.间充质干细胞通过细胞表面受体发挥免疫抑制作用。
Front Immunol. 2020 Jul 28;11:1076. doi: 10.3389/fimmu.2020.01076. eCollection 2020.
2
Mesenchymal stem cells transfected with sFgl2 inhibit the acute rejection of heart transplantation in mice by regulating macrophage activation.转染 sFgl2 的间充质干细胞通过调节巨噬细胞活化抑制小鼠心脏移植的急性排斥反应。
Stem Cell Res Ther. 2020 Jun 17;11(1):241. doi: 10.1186/s13287-020-01752-1.
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Extracellular vesicles derived from mesenchymal stem cells prevent skin fibrosis in the cGVHD mouse model by suppressing the activation of macrophages and B cells immune response.
Transplantation. 2025 Jul 1;109(7):1124-1137. doi: 10.1097/TP.0000000000005309. Epub 2025 Jan 27.
4
A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors.一项在小型和大型动物模型中进行的概念验证研究,旨在将肝脏常温机器灌注与间充质基质细胞生物反应器相结合。
Nat Commun. 2025 Jan 2;16(1):283. doi: 10.1038/s41467-024-55217-7.
5
Advancements in diabetic foot ulcer research: Focus on mesenchymal stem cells and their exosomes.糖尿病足溃疡研究进展:聚焦间充质干细胞及其外泌体
Heliyon. 2024 Aug 29;10(17):e37031. doi: 10.1016/j.heliyon.2024.e37031. eCollection 2024 Sep 15.
6
Regulatory cell therapy for kidney transplantation and autoimmune kidney diseases.调控细胞治疗在肾移植和自身免疫性肾脏疾病中的应用。
Pediatr Nephrol. 2025 Jan;40(1):39-52. doi: 10.1007/s00467-024-06514-2. Epub 2024 Sep 16.
7
Machine learning reveals the rules governing the efficacy of mesenchymal stromal cells in septic preclinical models.机器学习揭示了间充质基质细胞在脓毒症临床前模型中疗效的规律。
Stem Cell Res Ther. 2024 Sep 11;15(1):289. doi: 10.1186/s13287-024-03873-3.
8
The issue of heterogeneity of MSC-based advanced therapy medicinal products-a review.基于间充质干细胞的先进治疗药品的异质性问题——综述
Front Cell Dev Biol. 2024 Jul 26;12:1400347. doi: 10.3389/fcell.2024.1400347. eCollection 2024.
9
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Front Bioeng Biotechnol. 2024 Jul 10;12:1423864. doi: 10.3389/fbioe.2024.1423864. eCollection 2024.
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Analysis of HLA matching between deceased organ donors and cord blood units from a National Bank Network as a basis for potential platforms for chimerism-based immune tolerance after solid organ transplantation.分析国家银行网络中已故器官捐赠者与脐血单位之间的人类白细胞抗原(HLA)匹配情况,以此作为实体器官移植后基于嵌合体的免疫耐受潜在平台的基础。
Blood Transfus. 2025 May-Jun;23(3):250-254. doi: 10.2450/BloodTransfus.759. Epub 2024 Jun 10.
间充质干细胞来源的细胞外囊泡通过抑制巨噬细胞和 B 细胞免疫应答来预防 cGVHD 小鼠模型中的皮肤纤维化。
Int Immunopharmacol. 2020 Jul;84:106541. doi: 10.1016/j.intimp.2020.106541. Epub 2020 May 18.
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Cytoprotective Effects of Mesenchymal Stem Cells During Liver Transplantation From Donors After Cardiac Death in Swine.猪心脏死亡供体肝移植期间间充质干细胞的细胞保护作用
Transplant Proc. 2020 Jul-Aug;52(6):1891-1900. doi: 10.1016/j.transproceed.2020.01.165. Epub 2020 May 7.
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Mesenchymal stromal cells induce regulatory T cells via epigenetic conversion of human conventional CD4 T cells in vitro.间充质基质细胞在体外通过人类常规CD4 T细胞的表观遗传转化诱导调节性T细胞。
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Am J Transplant. 2020 Oct;20(10):2905-2915. doi: 10.1111/ajt.15910. Epub 2020 May 6.
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Mesenchymal stem cells regulate the Th17/Treg cell balance partly through hepatocyte growth factor in vitro.间充质干细胞通过肝细胞生长因子在体外部分调节 Th17/Treg 细胞平衡。
Stem Cell Res Ther. 2020 Feb 28;11(1):91. doi: 10.1186/s13287-020-01612-y.
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Differential effects of heat-inactivated, secretome-deficient MSC and metabolically active MSC in sepsis and allogenic heart transplantation.热灭活、缺乏外泌体的 MSC 和代谢活跃的 MSC 在脓毒症和同种异体心脏移植中的差异效应。
Stem Cells. 2020 Jun;38(6):797-807. doi: 10.1002/stem.3165. Epub 2020 Mar 12.
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Front Cell Dev Biol. 2020 Jan 29;8:10. doi: 10.3389/fcell.2020.00010. eCollection 2020.
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Effects of mesenchymal stromal cells on regulatory T cells: Current understanding and clinical relevance.间充质基质细胞对调节性 T 细胞的影响:当前认识和临床相关性。
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