Daneshmandi Saeed, Karimi Mohammad Hossein, Pourfathollah Ali Akbar
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Int Immunopharmacol. 2017 Mar;44:191-196. doi: 10.1016/j.intimp.2017.01.019. Epub 2017 Jan 19.
Mesenchymal stem cells (MSCs) are advantageous candidates for cell therapy of Type 1 diabetes (T1D). Considering immunomodulatory effect of MSC, in this study, we engineered MSCs with TGF-β gene to increase MSC potency for T1D therapy in mouse model.
Two plans were designed for prevention and treatment of diabetes, respectively. In both of them, MSCs were injected i.v. and then, the diabetes features including serum insulin, blood glucose, glucose tolerance, splenocytes proliferation, and IL-4/IFN-γ production were evaluated.
TGF-β/MSCs treatment program resulted in the restoration of serum glucose after 3weeks, while prevention program could delay diabetes progression for two weeks. TGF-β/MSCs treatment elevated the levels of serum insulin and Th2 cytokine shift on 5th week after start of treatment. TGF-β/MSCs (and MSCs alone) could also diminish body weight and enhance mice survival comparing to untreated diabetic mice.
Engineered TGF-β/MSCs could restore some T1D features, including the regulation of adverse immune responses and could be potent tools for cell therapy of T1D comparing MSCs alone.
间充质干细胞（MSCs）是1型糖尿病（T1D）细胞治疗的理想候选者。考虑到MSCs的免疫调节作用，在本研究中，我们用转化生长因子-β（TGF-β）基因改造MSCs，以提高其在小鼠模型中治疗T1D的效能。
分别设计了预防和治疗糖尿病的两个方案。在这两个方案中，均经静脉注射MSCs，然后评估包括血清胰岛素、血糖、葡萄糖耐量、脾细胞增殖以及白细胞介素-4/干扰素-γ产生等糖尿病特征。
TGF-β/MSCs治疗方案在3周后使血糖恢复正常，而预防方案可将糖尿病进展延缓两周。TGF-β/MSCs治疗在治疗开始后第5周提高了血清胰岛素水平并使Th2细胞因子发生偏移。与未治疗的糖尿病小鼠相比，TGF-β/MSCs（以及单独的MSCs）还可减轻体重并提高小鼠存活率。
经改造的TGF-β/MSCs可恢复一些T1D特征，包括调节不良免疫反应，与单独的MSCs相比，可能是T1D细胞治疗的有效工具。
