Diabetic microenvironment preconditioning of adipose tissue-derived mesenchymal stem cells enhances their anti-diabetic, anti-long-term complications, and anti-inflammatory effects in type 2 diabetic rats.
Diabetic microenvironment preconditioning of adipose tissue-derived mesenchymal stem cells enhances their anti-diabetic, anti-long-term complications, and anti-inflammatory effects in type 2 diabetic rats.
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脂肪组织间充质干细胞的糖尿病微环境预处理增强其对2型糖尿病大鼠的抗糖尿病、抗长期并发症和抗炎作用
DOI：
10.1186/s13287-022-03114-5
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发表时间：
2022-08-19
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
作者：
间充质干细胞（MSC）发挥抗糖尿病作用，并通过调节巨噬细胞极化和减轻炎症的分泌作用改善长期并发症。提高MSC的功效需要进一步探索。体外培养微环境影响MSCs的分泌特性。因此，我们假设糖尿病微环境将促进负责巨噬细胞极化的细胞因子的分泌，进一步减轻全身炎症并增强MSC对2型糖尿病（T2 D）和长期糖尿病并发症的影响。在糖尿病代谢环境（包括高糖、晚期糖基化终产物和脂多糖）中共培养脂肪来源的间充质干细胞（pre-ADSC）后获得预处理的脂肪来源的间充质干细胞（pre-ADSC）。体外观察前脂肪干细胞对巨噬细胞的调节作用。用高脂饮食32周结合腹腔注射链脲佐菌素诱导T2 D大鼠模型。将SD大鼠分为正常组、糖尿病未治疗组（PBS）、ADSC治疗组和ADSC前治疗组。每周静脉注射ADSC和pre-ADSC给SD大鼠，持续6个月，然后评价各组的葡萄糖稳态和长期糖尿病并发症。与M2巨噬细胞极化相关的细胞因子（IL-6、MCP-1等）的分泌在体外模型中，在pre-ADSC组中增加。与ADSC组相比，ADSC预处理显著维持血糖稳态，降低胰岛素抵抗，促进胰岛再生，并改善大鼠中与糖尿病相关的并发症（慢性肾病、非酒精性脂肪性肝炎、肺纤维化和白内障）（P < 0.05）。此外，在预ADSC注射后，组织中抗炎M2巨噬细胞表型的数量增加。此外，与pre-ADSCs一起培养后，促炎基因（iNOS、TNF-α、IL-1β）的表达降低，而抗炎基因（Arg 1、CD 206和IL-10）的表达增加。糖尿病微环境预处理的脂肪干细胞可有效增强机体抗炎症能力，调节T2 D远期并发症的进展。在线版本包含补充材料，可通过10.1186/s13287-022-03114-5获得。
Mesenchymal stem cells (MSCs) exert anti-diabetic effects and improve long-term complications via secretory effects that regulate macrophage polarisation and attenuate inflammation. Enhancing the efficacy of MSCs needs to be explored further. The in vitro culture microenvironment influences the secretory profile of MSCs. Therefore, we hypothesised that a diabetic microenvironment would promote the secretion of cytokines responsible for macrophage polarisation, further attenuating systemic inflammation and enhancing the effects of MSCs on type 2 diabetes (T2D) and long-term diabetic complications. Preconditioned adipose-derived mesenchymal stem cells (pre-ADSCs) were obtained after co-cultivating ADSCs in a diabetic metabolic environment (including high sugar, advanced glycation end-product, and lipopolysaccharides). The regulatory effects of pre-ADSCs on macrophages were observed in vitro. A T2D rat model was induced with a high-fat diet for 32 weeks combined with an intraperitoneal injection of streptozotocin. Sprague–Dawley (SD) rats were divided into four groups: normal group, diabetes without treatment group (PBS), ADSC treatment group, and pre-ADSC treatment group. ADSCs and pre-ADSCs were intravenously administered weekly to SD rats for 6 months, and then glucose homeostasis and long-term diabetic complications were evaluated in each group. The secretion of cytokines related to M2 macrophage polarisation (IL-6, MCP-1, etc.) was increased in the pre-ADSC group in the in vitro model. Pre-ADSC treatment significantly maintained blood glucose homeostasis, reduced insulin resistance, promoted islet regeneration, and ameliorated the complications related to diabetes in rats (chronic kidney disease, non-alcoholic steatohepatitis, lung fibrosis, and cataract) compared to the ADSC group (P < 0.05). Additionally, the number of anti-inflammatory M2 macrophage phenotypes was enhanced in tissues following pre-ADSC injections. Moreover, the expression of pro-inflammatory genes (iNOS, TNF-α, IL-1β) was reduced whereas that of anti-inflammatory genes (Arg1, CD206, and Il-10) was increased after cultivation with pre-ADSCs. Diabetic microenvironment-preconditioned ADSCs effectively strengthen the capacity against inflammation and modulate the progress of long-term T2D complications. The online version contains supplementary material available at 10.1186/s13287-022-03114-5.
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影响因子：
7.3
作者：
Kraakman MJ;Murphy AJ;Jandeleit-Dahm K;Kammoun HL
通讯作者：
Kammoun HL
使用脂肪组织来源的间充质干细胞治疗可发挥抗糖尿病作用，改善长期并发症，并减轻 2 型糖尿病大鼠的炎症
影响因子：
7.5
作者：
Yu, Songyan;Cheng, Yu;Mu, Yiming
通讯作者：
Mu, Yiming
影响因子：
2.5
作者：
Nguyen, Duy;Ping, Fu;Chadban, Steven J.
通讯作者：
Chadban, Steven J.
影响因子：
8.1
作者：
Jiang, Ranhua;Han, Zhibo;Han, Zhong Chao
通讯作者：
Han, Zhong Chao
影响因子：
5.2
作者：
Rosova, Ivana;Dao, Mo;Nolta, Jan A.
通讯作者：
Nolta, Jan A.