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