Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
Cytotherapy. 2011 Jan;13(1):19-29. doi: 10.3109/14653249.2010.518608.
Recent evidence has suggested that transplanted bone marrow (BM)-derived mesenchymal stromal cells (MSC) are able to engraft and repair non-hematopoietic tissues successfully, including central nervous system, renal, pulmonary and skin tissue, and may possibly contribute to tissue regeneration. We examined the cytoprotective effect of BM MSC on co-cultured, isolated pancreatic islets.
Pancreatic islets and MSC isolated from Lewis rats were divided into four experimental groups: (a) islets cultured alone (islet control); (b) islets cultured in direct contact with MSC (IM-C); (c) islets co-cultured with MSC in a Transwell system, which allows indirect cell contact through diffusible media components (IM-I); and (d) MSC cultured alone (MSC control). The survival and function of islets were measured morphologically and by analyzing insulin secretion in response to glucose challenge. Cytokine profiles were determined using a cytokine array and enzyme-linked immunosorbent assays.
Islets contact-cultured with MSC (IM-C) showed sustained survival and retention of glucose-induced insulin secretory function. In addition, the levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) were decreased, and tissue inhibitor of metalloproteinases-1 (TIMP-1) and vascular endothelial growth factor (VEGF) levels were increased at 4 weeks in both the IM-C and IM-I groups.
These results indicate that contact co-culture is a major factor that contributes to islet survival, maintenance of cell morphology and insulin function. There might also be a synergic effect resulting from the regulation of inflammatory cytokine production. We propose that BM MSC are suitable for generating a microenvironment favorable for the repair and longevity of pancreatic islets.
最近的证据表明，移植的骨髓（BM）衍生间充质基质细胞（MSC）能够成功植入和修复非造血组织，包括中枢神经系统、肾脏、肺和皮肤组织，并可能有助于组织再生。我们研究了 BM MSC 对共培养的分离胰岛的细胞保护作用。
从 Lewis 大鼠中分离的胰岛和 MSC 被分为四个实验组：（a）单独培养的胰岛（胰岛对照）；（b）与 MSC 直接接触培养的胰岛（IM-C）；（c）通过 Transwell 系统共培养的胰岛，该系统允许通过可扩散的介质成分进行间接细胞接触（IM-I）；和（d）单独培养的 MSC（MSC 对照）。通过形态学和分析葡萄糖刺激下的胰岛素分泌来测量胰岛的存活和功能。使用细胞因子阵列和酶联免疫吸附测定法确定细胞因子谱。
与 MSC 接触培养的胰岛（IM-C）显示出持续的存活和保留葡萄糖诱导的胰岛素分泌功能。此外，在第 4 周时，IM-C 和 IM-I 组中单核细胞趋化蛋白-1（MCP-1）和肿瘤坏死因子-α（TNF-α）的水平降低，组织金属蛋白酶抑制剂-1（TIMP-1）和血管内皮生长因子（VEGF）水平升高。
这些结果表明，接触共培养是促进胰岛存活、维持细胞形态和胰岛素功能的主要因素。炎性细胞因子产生的调节也可能存在协同作用。我们提出 BM MSC 适合产生有利于胰岛修复和长寿的微环境。
