Type 1 diabetes (T1D) is a chronic autoimmune disease destroying the insulin-producing beta cells. Recently, stem cell therapy has been tested to treat T1D. In the present study, we aim to investigate the effects of intraperitoneal and intravenous infusion of multipotent mesenchymal stem/stromal cells (MSCs) and MSC-conditioned medium (MSC-CM) in an experimental model of diabetes, induced by multiple injections of Streptozotocin (STZ). The adipose tissue-derived MSC and MSC-CM were isolated from C57Bl/6 male mice and characterized. Later, MSC and MSC-CM were injected intraperitoneally or intravenously into mice. The blood glucose, urinary glucose, and body weight were measured, and the percentages of CD4+ CD25+ FOXP3+ T cells as well as the levels of IFN-γ, TGF-β, IL-4, IL-17, and IL-10 were evaluated. Our results showed that both intraperitoneal and intravenous infusions of MSC and MSC-CM could decrease the blood glucose, recover pancreatic islets, and increase the levels of insulin-producing cells. Furthermore, the percentage of CD4+ CD25+ FOXP3+ T cells was increased after intraperitoneal injection of MSC or MSC-CM and intravenous injection of MSCs. After intraperitoneal injection of the MSC and MSC-CM, the levels of inflammatory cytokines reduced, while the levels of anti-inflammatory cytokines increased. Together current data showed that although both intraperitoneal and intravenous administration had beneficial effects on T1D animal model, but intraperitoneal injection of AD-MSC and AD-MSC-CM was more effective than systemic administration.

中文翻译：

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研究1型糖尿病小鼠中脂肪组织间充质干细胞和条件培养基的给药途径和功效。

1型糖尿病（T1D）是一种慢性自身免疫性疾病，会破坏产生胰岛素的β细胞。最近，已经测试了干细胞疗法来治疗T1D。在本研究中，我们旨在研究腹膜内和静脉内输注多能间充质干细胞/基质细胞（MSCs）和MSC条件培养基（MSC-CM）在多次注射链脲佐菌素（ STZ）。从C57Bl / 6雄性小鼠中分离并表征脂肪组织来源的MSC和MSC-CM。之后，将MSC和MSC-CM腹膜内或静脉内注射入小鼠。测量血糖，尿葡萄糖和体重，并评估CD4 + CD25 + FOXP3 + T细胞的百分比以及IFN-γ，TGF-β，IL-4，IL-17和IL-10的水平。我们的结果表明，腹膜内和静脉内输注MSC和MSC-CM均可降低血糖，恢复胰岛并增加胰岛素产生细胞的水平。此外，腹膜内注射MSC或MSC-CM和静脉注射MSC后，CD4 + CD25 + FOXP3 + T细胞的百分比增加。腹膜内注射MSC和MSC-CM后，炎症细胞因子水平降低，而抗炎细胞因子水平升高。在一起的最新数据表明，尽管腹膜内和静脉内给药对T1D动物模型均具有有益的作用，但腹膜内注射AD-MSC和AD-MSC-CM比全身给药更有效。恢复胰腺胰岛，并增加胰岛素产生细胞的水平。此外，腹膜内注射MSC或MSC-CM和静脉注射MSC后，CD4 + CD25 + FOXP3 + T细胞的百分比增加。腹膜内注射MSC和MSC-CM后，炎症细胞因子水平降低，而抗炎细胞因子水平升高。在一起的最新数据表明，尽管腹膜内和静脉内给药对T1D动物模型均具有有益的作用，但腹膜内注射AD-MSC和AD-MSC-CM比全身给药更有效。恢复胰腺胰岛，并增加胰岛素产生细胞的水平。此外，腹膜内注射MSC或MSC-CM和静脉注射MSC后，CD4 + CD25 + FOXP3 + T细胞的百分比增加。腹膜内注射MSC和MSC-CM后，炎症细胞因子水平降低，而抗炎细胞因子水平升高。在一起的最新数据表明，尽管腹膜内和静脉内给药对T1D动物模型均具有有益的作用，但腹膜内注射AD-MSC和AD-MSC-CM比全身给药更有效。腹膜内注射MSC和MSC-CM后，炎症细胞因子水平降低，而抗炎细胞因子水平升高。在一起的最新数据表明，尽管腹膜内和静脉内给药对T1D动物模型均具有有益的作用，但腹膜内注射AD-MSC和AD-MSC-CM比全身给药更有效。腹膜内注射MSC和MSC-CM后，炎症细胞因子水平降低，而抗炎细胞因子水平升高。在一起的最新数据表明，尽管腹膜内和静脉内给药对T1D动物模型均具有有益的作用，但腹膜内注射AD-MSC和AD-MSC-CM比全身给药更有效。