Amer Mona G, Embaby Azza S, Karam Rehab A, Amer Marwa G
Histology & Cell Biology, Faculty of Medicine, Zagazig University, Egypt; Anatomy and histology department, College of medicine, Taif University, Saudi Arabia.
Histology & Cell Biology, Faculty of Medicine, Beni-Sueif University, Egypt.
Gene. 2018 May 15;654:87-94. doi: 10.1016/j.gene.2018.02.008. Epub 2018 Feb 13.
Generation of new β cells is an important approach in the treatment of type 1 diabetes mellitus (type 1 DM). Adipose tissue-derived stem cells (ADSCs) might be one of the best sources for cell replacement therapy for diabetes. Therefore, this work aimed to test the possible role of transplanted insulin-producing cells (IPCs) differentiated from ADSCs in treatment of streptozotocin (STZ) induced type I DM in rats. Type 1 DM was induced by single intra peritoneal injection with STZ (50 mg/kg BW). Half of the diabetic rats were left without treatment and the other half were injected with differentiated IPCs directly into the pancreas. ADSCs were harvested, cultured and identified by testing their phenotypes through flow cytometry. They were further subjected to differentiation into IPCs using differentiation medium. mRNA expression of pancreatic transcription factors (pdx1), insulin and glucose transporter-2 genes by real time PCR was done to detect the cellular differentiation and confirmed by stimulated insulin secretion. The pancreatic tissues from all groups were examined 2 months after IPC transplantation and were subjected to histological, Immunohistochemical and morphometric study. The differentiated IPCs showed significant expression of pancreatic β cell markers and insulin secretion in glucose dependent manner. Treatment with IPCs induced apparent regeneration, diffused proliferated islet cells and significant increase in C-peptide immune reaction. We concluded that transplantation of differentiated IPCs improved function and morphology of Islet cells in diabetic rats. Consequently, this therapy option may be a promising therapeutic approach to patient with type 1 DM if proven to be effective and safe.
生成新的β细胞是治疗1型糖尿病（1型糖尿病）的重要方法。脂肪组织来源的干细胞（ADSCs）可能是糖尿病细胞替代治疗的最佳来源之一。因此，本研究旨在测试从ADSCs分化而来的移植胰岛素产生细胞（IPCs）在治疗链脲佐菌素（STZ）诱导的大鼠1型糖尿病中的可能作用。通过单次腹腔注射STZ（50mg/kg体重）诱导1型糖尿病。一半的糖尿病大鼠不进行治疗，另一半直接将分化的IPCs注射到胰腺中。收获ADSCs，通过流式细胞术检测其表型进行培养和鉴定。使用分化培养基将它们进一步诱导分化为IPCs。通过实时PCR检测胰腺转录因子（pdx1）、胰岛素和葡萄糖转运蛋白-2基因的mRNA表达以检测细胞分化，并通过刺激胰岛素分泌进行确认。在IPCs移植2个月后检查所有组的胰腺组织，并进行组织学、免疫组织化学和形态计量学研究。分化的IPCs以葡萄糖依赖的方式显示出胰腺β细胞标志物的显著表达和胰岛素分泌。用IPCs治疗诱导了明显的再生、胰岛细胞的弥漫性增殖以及C肽免疫反应的显著增加。我们得出结论，分化的IPCs移植改善了糖尿病大鼠胰岛细胞的功能和形态。因此，如果被证明有效且安全，这种治疗选择可能是1型糖尿病患者一种有前景的治疗方法。
