骨髓间充质细胞联合PDMS支架构建移植胰岛微环境的实验研究

目的为了提高移植胰岛的活性和功能,构建适合移植胰岛生存的微环境。 方法采用聚二甲基硅氧烷（PDMS）和氯化钠晶体构建三维支架,联合骨髓间充质细胞（MSCs）、纤维蛋白和胰岛共同构建迷你"人工胰腺"。采用链脲佐菌素（STZ）诱导的糖尿病大鼠移植模型评价效果,将"人工胰腺"移植到糖尿病大鼠大网膜内,对照组行假手术,术后隔天监测移植大鼠血糖水平;数据采用t检验和曼-惠特尼U检验。 结果用PDMS构建的三维巨孔支架,支架内可见大量不规则孔洞空间。胰岛和MSCs可成功装载入支架内,HE染色结果显示,支架孔内存在胰岛,胰岛周围包绕有MSCs。糖尿病大鼠大网膜内移植结果显示,移植后各时间点（1,3,5,7 d）,"人工胰腺"移植组糖尿病大鼠血糖水平分别为（278.70±86.06）mg/ dl、（323.50±44.29）mg/ dl、（283.30±74.00）mg/dl、（304.80±13.33）mg/dl,较假手术对照组（606.00±52.40）mg/dl、（589.70±55.78）mg/dl、（615.00±54.84）mg/dl、（630.30±48.17）mg/ dl均降低,差异具有统计学意义（t = 7.96、9.15、8.82,U = 0.00,P均< 0.01）。 结论MSCs联合PDMS三维支架构建的微环境,可为移植胰岛提供生存的环境,为临床开展胰岛移植提供新的策略。

Engineer a microenvironment for islet transplantation with bone marrow mesenchymal stroma cells and PDMS scaffold

ObjectiveThe study was aimed to engineer a suitable microenvironment for islets survival. MethodsThe three-dimensional macroporous scaffold was constructed with polydimethylsiloxane (PDMS) and sodium chloride crystal. The mini "artificial pancreas" was engineered with PDMS scaffold, bone marrow mesenchymal stroma cells (MSCs), fibronectin and islets. The artificial pancreases were transplanted into the omentum of STZ-induced diabetic rats, while the control group underwent sham operation. The blood glucose level of the rats was monitored every other day; the data was analyzed by t test and Kolmogorov-Smirnov test/Mann-Whitney test. ResultsThe PDMS scaffolds were constructed successfully with a large number of macro-pores. Islets and MSCs can be loaded into the scaffolds. HE staining showed that there were islets in the scaffold pores with surrounding MSCs. At each time point after transplantation (1, 3, 5, 7 days), the blood glucose levels of diabetic rats in artificial pancreas transplantation group were (278.70±86.06) mg/dl; (323.50±44.29) mg/dl; (283.30±74.0) mg/dl; and (304.80±13.33) mg/ dl respectively, which were significantly decreased than those in the control respectively group (606.00±52.40) mg/dl, (589.70±55.78) mg/dl, (615.00±54.84) mg/dl, (630.30±48.17) mg/ dl, (t = 7.96、9.15、8.82, U = 0.00, P < 0.01). ConclusionThe microenvironment engineered with bone marrow MSCs and PDMS scaffold could provide a suitable environment for transplanted islets and provide a new strategy for clinical islet transplantation.