Pancreatic Centre, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Ave 1277, Wuhan City, Hubei Province 430022, People's Republic of China.
Cell Biol Int. 2012 Sep;36(9):823-31. doi: 10.1042/CBI20110680.
The implantation of BMSCs (bone marrow mesenchymal stem cells) has emerged as a potential method of treating tissue damage, but the in vivo differentiation of BMSCs in an injured pancreas and its therapeutic effects have not been determined. Our aim has been to investigate the potential of BMSCs to contribute to the parenchyma and mesenchymal components of the pancreas during rapid regeneration, with preliminary exploration of the molecular mechanisms of this process. GFP(+) (green fluorescent protein(+) ) BMSCs were intravenously infused into the tail veins of mice that had received a 65-70% partial pancreatectomy, while mice that had only received a partial pancreatectomy and mice that had only been injected with BMSCs served as controls. Four weeks later, the injected GFP(+) BMSCs were diffusely engrafted in the pancreatic parenchyma and mesenchyma of the recipient mice with pancreatic injuries and had differentiated into pancreatic ductal epithelial cells (accounting for 1.7±0.3%), vascular endothelial cells (3.2±0.6%) and PSCs (pancreatic stellate cells) (5.2±1.6%), but no β or neural cells. Significantly, more engrafted and differentiated GFP(+) BMSCs were observed in the regenerating pancreas than in the normal pancreas. For the mice that received a partial pancreatectomy, the pancreatic weight/body weight of the mice with BMSC treatment was greater than mice without BMSC treatment (P<0.05). In addition, real-time RT-PCR (reverse transcription-PCR) showed that the expression levels of miR-9 (microRNA 9) and miR-204 in the engrafted BMSCs (5.2- and 2.6-fold, P<0.05, respectively) were increased compared with wild-type BMSCs. We also observed a significant reduction in the expression of miR-375 (0.71-fold, P<0.05) in engrafted GFP(+) BMSCs compared with wild-type BMSCs. BMSCs can therefore be a potential cell bank for treating pancreatic injuries by contributing to a variety of cell types. This process might be related to the expression of miR-9, miR-204 and miR-375.
骨髓间充质干细胞（BMSCs）的移植已成为治疗组织损伤的一种有潜力的方法，但 BMSCs 在受伤胰腺中的体内分化及其治疗效果尚未确定。我们的目的是研究 BMSCs 在胰腺快速再生过程中对实质和间质成分的潜在贡献，并初步探索这一过程的分子机制。将 GFP（+）（绿色荧光蛋白（+））BMSCs 静脉内注入接受 65-70%部分胰腺切除术的小鼠的尾静脉中，而仅接受部分胰腺切除术的小鼠和仅注射 BMSCs 的小鼠作为对照。四周后，注射的 GFP（+）BMSCs 弥散地植入受损伤胰腺的胰腺实质和间质中，并分化为胰腺导管上皮细胞（占 1.7±0.3%）、血管内皮细胞（3.2±0.6%）和 PSCs（胰腺星状细胞）（5.2±1.6%），但没有 β 细胞或神经细胞。值得注意的是，在再生胰腺中观察到更多的植入和分化的 GFP（+）BMSCs。对于接受部分胰腺切除术的小鼠，接受 BMSC 治疗的小鼠的胰腺重量/体重比未接受 BMSC 治疗的小鼠更大（P<0.05）。此外，实时 RT-PCR（逆转录-PCR）显示，植入的 BMSCs 中 miR-9（microRNA 9）和 miR-204 的表达水平分别增加了 5.2 倍和 2.6 倍（P<0.05），与野生型 BMSCs 相比。我们还观察到植入的 GFP（+）BMSCs 中 miR-375 的表达显著降低（0.71 倍，P<0.05），与野生型 BMSCs 相比。因此，BMSCs 可以通过贡献多种细胞类型成为治疗胰腺损伤的潜在细胞库。这一过程可能与 miR-9、miR-204 和 miR-375 的表达有关。
