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慢性胰腺炎患者的间充质干细胞与健康供者的细胞相比具有相当的功效。

Mesenchymal Stem Cells from Chronic Pancreatitis Patients Show Comparable Potency Compared to Cells from Healthy Donors.

机构信息

Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.

College of Life Science, Qingdao Agricultural University, Qingdao, People's Republic of China.

出版信息

Stem Cells Transl Med. 2019 May;8(5):418-429. doi: 10.1002/sctm.18-0093. Epub 2019 Jan 24.

Abstract

Mesenchymal stem cells (MSCs) are proven to be beneficial in islet transplantation, suggesting a potential therapeutic role of them in total pancreatectomy with islet autotransplantation (TP-IAT) for chronic pancreatitis (CP) patients. We investigated whether MSCs derived from CP patients are suitable for use in autologous cell therapy. MSCs from healthy donors (H-MSCs) and CP patients (CP-MSCs) were studied for phenotype, colony formation potential, multilineage differentiation ability, proliferation, senescence, secretory characters, and immunosuppressive functions. The potential protective effect of CP-MSCs was evaluated on hypoxia-induced islet cell death. Cell surface markers were similar between H-MSCs and CP-MSCs, as well as the ability of colony formation, multilineage differentiation, secretion of vascular endothelial growth factor and transforming growth factor (TGF-β), senescence, and inhibition of T cells proliferation in vitro. We found that growth differentiation factor 6 and hepatocyte growth factor (HGF) were significantly downregulated, whereas TGFβ and matrix metalloproteinase-2 were significantly upregulated in CP-MSCs compared with H-MSCs, among 84 MSC-related genes investigated in this study. MSCs from CP patients secreted less HGF, compared with the H-MSCs. A higher interferon-γ-induced indoleamine 2,3-dioxygenase expression was observed in CP-MSCs compared to H-MSCs. Moreover, CP-MSCs prevented hypoxia-induced β cell deaths to a similar extent as H-MSCs. Regardless of moderate difference in gene expression, CP-MSCs possess similar immunomodulatory and prosurvival functions to H-MSCs, and may be suitable for autologous cell therapy in CP patients undergoing TP-IAT. Stem Cells Translational Medicine 2019;8:418-429.

摘要

间充质干细胞(MSCs)在胰岛移植中被证明是有益的,这表明它们在慢性胰腺炎(CP)患者的全胰腺切除术伴胰岛自体移植(TP-IAT)中具有潜在的治疗作用。我们研究了 CP 患者来源的 MSCs 是否适合用于自体细胞治疗。研究了来自健康供体(H-MSCs)和 CP 患者(CP-MSCs)的 MSCs 的表型、集落形成潜能、多能分化能力、增殖、衰老、分泌特性和免疫抑制功能。评估了 CP-MSCs 对缺氧诱导的胰岛细胞死亡的潜在保护作用。H-MSCs 和 CP-MSCs 之间的细胞表面标志物相似,集落形成能力、多能分化能力、血管内皮生长因子和转化生长因子(TGF-β)的分泌、衰老以及体外 T 细胞增殖的抑制能力也相似。我们发现,与 H-MSCs 相比,CP-MSCs 中的生长分化因子 6 和肝细胞生长因子(HGF)明显下调,而 TGFβ 和基质金属蛋白酶-2 明显上调,在本研究中调查的 84 个 MSC 相关基因中。与 H-MSCs 相比,CP 患者来源的 MSCs 分泌的 HGF 较少。与 H-MSCs 相比,CP-MSCs 中干扰素-γ诱导的吲哚胺 2,3-双加氧酶表达更高。此外,CP-MSCs 防止缺氧诱导的β细胞死亡的程度与 H-MSCs 相似。尽管基因表达存在适度差异,但 CP-MSCs 具有与 H-MSCs 相似的免疫调节和促生存功能,并且可能适合 CP 患者接受 TP-IAT 时进行自体细胞治疗。《干细胞转化医学》2019;8:418-429。

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