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异种骨髓来源间充质干细胞共移植减轻非肥胖糖尿病小鼠胰岛的排斥反应

Co-transplantation of Xenogeneic Bone Marrow-derived Mesenchymal Stem Cells Alleviates Rejection of Pancreatic Islets in Non-obese Diabetic Mice.

作者信息

Corradi-Perini C, Santos T M, Camara N O S, Riella M C, Aita C A M

机构信息

School of Life Sciences, Pontifical Catholic University of Parana, Curitiba, Brazil.

Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.

出版信息

Transplant Proc. 2017 May;49(4):902-905. doi: 10.1016/j.transproceed.2017.01.064.

DOI:10.1016/j.transproceed.2017.01.064
PMID:28457422
Abstract

Bone marrow-mesenchymal stem cells (BM-MSCs) have generated a great perspective in the field of regenerative medicine, and also in the treatment of inflammatory and autoimmune diseases in the past decade due to their immunomodulatory and anti-inflammatory properties. Here, we investigated the effect of xenogeneic BM-MSCs and pancreatic islets co-transplantation obtained from Wistar rats in preventing rejection or inducing tolerance to islet transplantation in non-obese diabetic mice. Non-obese diabetic mice were treated with co-transplantation of pancreatic islets and BM-MSCs (islet + MSCs group) or pancreatic islets only (islet group). Compared to the islet group, islet + MSCs had a lower expression of inflammatory markers, such as, tumor necrosis factor- α (13.40 ± 0.57 vs. 9.90 ± 0.12, P = .01), monocyte chemoattractant protein 1 (51.30 ± 6.80 vs. 9.00 ± 1.80, P = .01), and interleukin 1β (IL-1β) (16.2 ± 1.65 vs. 6.80 ± 1.00, P = .04). Comparing the expression of immune tolerance markers, it is noted that animals receiving the co-transplantation showed a significantly higher expression than the islet group of IL-4 (25.60 ± 1.96 vs. 2.80 ± 0.20, P = .004), IL-10 (188.40 ± 4.60 vs. 4.55 ± 0.12, P = .0001), and forkhead box P3 (34.20 ± 1.3 vs. 1.30 ± 0.2, P = .004), respectively. These results suggest an immunomodulatory action of BM-MSC in islet xenotransplantation showing that these stem cells have the potential to mitigate the early losses of grafts, due to the regulation of the inflammatory process of transplantation.

摘要

在过去十年中,骨髓间充质干细胞(BM-MSCs)因其免疫调节和抗炎特性,在再生医学领域以及炎症和自身免疫性疾病的治疗中展现出广阔前景。在此,我们研究了从Wistar大鼠获得的异种BM-MSCs与胰岛共同移植,对非肥胖糖尿病小鼠预防胰岛移植排斥或诱导免疫耐受的作用。非肥胖糖尿病小鼠接受胰岛和BM-MSCs共同移植(胰岛+MSCs组)或仅接受胰岛移植(胰岛组)。与胰岛组相比,胰岛+MSCs组炎症标志物的表达较低,如肿瘤坏死因子-α(13.40±0.57对9.90±0.12,P = 0.01)、单核细胞趋化蛋白1(51.30±6.80对9.00±1.80,P = 0.01)和白细胞介素1β(IL-1β)(16.2±1.65对6.80±1.00,P = 0.04)。比较免疫耐受标志物的表达发现,接受共同移植的动物IL-4(25.60±1.96对2.80±0.20,P = 0.004)、IL-10(188.40±4.60对4.55±0.12,P = 0.0001)和叉头框P3(34.20±1.3对1.30±0.2,P = 0.004)的表达明显高于胰岛组。这些结果表明BM-MSC在胰岛异种移植中具有免疫调节作用,显示这些干细胞有潜力减轻移植早期移植物的损失,这归因于对移植炎症过程的调节。

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Co-transplantation of Xenogeneic Bone Marrow-derived Mesenchymal Stem Cells Alleviates Rejection of Pancreatic Islets in Non-obese Diabetic Mice.异种骨髓来源间充质干细胞共移植减轻非肥胖糖尿病小鼠胰岛的排斥反应
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Stem Cell Res Ther. 2024 Oct 29;15(1):384. doi: 10.1186/s13287-024-03974-z.
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Stem Cell Therapy Improves Human Islet Graft Survival in Mice via Regulation of Macrophages.干细胞疗法通过调节巨噬细胞改善人胰岛移植物在小鼠中的存活。
Diabetes. 2022 Dec 1;71(12):2642-2655. doi: 10.2337/db22-0117.
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Stem Cell Therapy and Hydrogen Sulfide: Conventional or Nonconventional Mechanisms of Action?
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Shock. 2020 Jun;53(6):737-743. doi: 10.1097/SHK.0000000000001420.
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Stem cells as a potential therapy for diabetes mellitus: a call-to-action in Latin America.干细胞作为糖尿病的一种潜在疗法:拉丁美洲的行动呼吁。
Diabetol Metab Syndr. 2019 Feb 18;11:20. doi: 10.1186/s13098-019-0415-0. eCollection 2019.