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用于治疗肾损伤的干细胞/基质细胞:聚焦临床前模型

Stem/Stromal Cells for Treatment of Kidney Injuries With Focus on Preclinical Models.

作者信息

Torres Crigna Adriana, Daniele Cristina, Gamez Carolina, Medina Balbuena Sara, Pastene Diego O, Nardozi Daniela, Brenna Cinzia, Yard Benito, Gretz Norbert, Bieback Karen

机构信息

Medical Faculty Mannheim, Institute of Transfusion Medicine and Immunology, University of Heidelberg, German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany.

Medical Faculty Mannheim, Medical Research Centre, University of Heidelberg, Mannheim, Germany.

出版信息

Front Med (Lausanne). 2018 Jun 15;5:179. doi: 10.3389/fmed.2018.00179. eCollection 2018.

DOI:10.3389/fmed.2018.00179
PMID:29963554
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6013716/
Abstract

Within the last years, the use of stem cells (embryonic, induced pluripotent stem cells, or hematopoietic stem cells), Progenitor cells (e.g., endothelial progenitor cells), and most intensely mesenchymal stromal cells (MSC) has emerged as a promising cell-based therapy for several diseases including nephropathy. For patients with end-stage renal disease (ESRD), dialysis or finally organ transplantation are the only therapeutic modalities available. Since ESRD is associated with a high healthcare expenditure, MSC therapy represents an innovative approach. In a variety of preclinical and clinical studies, MSC have shown to exert renoprotective properties, mediated mainly by paracrine effects, immunomodulation, regulation of inflammation, secretion of several trophic factors, and possibly differentiation to renal precursors. However, studies are highly diverse; thus, knowledge is still limited regarding the exact mode of action, source of MSC in comparison to other stem cell types, administration route and dose, tracking of cells and documentation of therapeutic efficacy by new imaging techniques and tissue visualization. The aim of this review is to provide a summary of published studies of stem cell therapy in acute and chronic kidney injury, diabetic nephropathy, polycystic kidney disease, and kidney transplantation. Preclinical studies with allogeneic or xenogeneic cell therapy were first addressed, followed by a summary of clinical trials carried out with autologous or allogeneic hMSC. Studies were analyzed with respect to source of cell type, mechanism of action etc.

摘要

在过去几年中,干细胞(胚胎干细胞、诱导多能干细胞或造血干细胞)、祖细胞(如内皮祖细胞),尤其是间充质基质细胞(MSC)已成为包括肾病在内的多种疾病颇具前景的细胞疗法。对于终末期肾病(ESRD)患者,透析或最终的器官移植是仅有的可用治疗方式。由于ESRD与高昂的医疗费用相关,MSC疗法代表了一种创新方法。在各种临床前和临床研究中,MSC已显示出具有肾脏保护特性,主要通过旁分泌作用、免疫调节、炎症调节、多种营养因子的分泌以及可能向肾前体细胞的分化来介导。然而,研究差异很大;因此,关于确切的作用方式、与其他干细胞类型相比MSC的来源、给药途径和剂量、细胞追踪以及通过新的成像技术和组织可视化记录治疗效果等方面的知识仍然有限。本综述的目的是总结已发表的关于干细胞疗法在急性和慢性肾损伤、糖尿病肾病、多囊肾病和肾移植中的研究。首先介绍了同种异体或异种细胞疗法的临床前研究,随后总结了使用自体或同种异体人MSC进行的临床试验。对研究进行了细胞类型来源、作用机制等方面的分析。

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Clinical-grade human skin-derived ABCB5+ mesenchymal stromal cells exert anti-apoptotic and anti-inflammatory effects and modulate mRNA expression in a cisplatin-induced kidney injury murine model.临床级人皮肤来源的ABCB5+间充质基质细胞在顺铂诱导的肾损伤小鼠模型中发挥抗凋亡和抗炎作用并调节mRNA表达。
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Adipose Stromal Cell-Derived Secretome Attenuates Cisplatin-Induced Injury In Vitro Surpassing the Intricate Interplay between Proximal Tubular Epithelial Cells and Macrophages.脂肪基质细胞衍生的分泌组减轻顺铂诱导的体外损伤,超越近端肾小管上皮细胞和巨噬细胞之间的复杂相互作用。
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Adipose-derived mesenchymal stem cells employed exosomes to attenuate AKI-CKD transition through tubular epithelial cell dependent Sox9 activation.脂肪来源的间充质干细胞利用外泌体通过肾小管上皮细胞依赖性Sox9激活来减轻急性肾损伤向慢性肾病的转变。
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