Treatment with adipose tissue-derived mesenchymal stem cells exerts anti-diabetic effects, improves long-term complications, and attenuates inflammation in type 2 diabetic rats
Treatment with adipose tissue-derived mesenchymal stem cells exerts anti-diabetic effects, improves long-term complications, and attenuates inflammation in type 2 diabetic rats
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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
DOI：
10.1186/s13287-019-1474-8
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发表时间：
2019-11-20
影响因子：
7.5
通讯作者：
Mu, Yiming
中科院分区：
文献类型：
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作者：
Yu, Songyan;Cheng, Yu;Mu, Yiming
背景糖尿病相关的长期并发症是糖尿病患者发病和死亡的主要原因。这些糖尿病并发症与免疫系统激活密切相关，沿着慢性、非消退性炎症，但直接逆转这些并发症的疗法仍然不可用。我们以前的研究表明，间充质干细胞（MSCs）减轻2型糖尿病（T2 DM）的慢性炎症，从而改善胰岛素敏感性和胰岛功能。因此，我们推测，骨髓间充质干细胞可能发挥抗炎作用，并促进逆转糖尿病诱导的肾脏，肝脏，肺，心脏，和透镜疾病在T2 DM rats.MethodsWe诱导长期T2 DM并发症大鼠模型，通过使用低剂量的链脲佐菌素（STZ）与高脂饮食（HFD）的组合32周。脂肪来源的间充质干细胞（ADSC）每周全身给药一次，持续24周。然后，我们研究了脂肪干细胞的作用，在调制的进展，长期diabeticcomplication.ResultsMultiple输注脂肪干细胞衰减慢性肾脏疾病（CKD），非酒精性脂肪性肝炎（NASH），肺纤维化，白内障，改善心脏功能，并降低血脂水平在T2 DM大鼠。此外，各组动物血清中炎性细胞因子的水平显示，ADSC输注不仅能够抑制促炎细胞因子IL-6、IL-1β和TNF-α的表达，而且还系统地增加抗炎细胞因子IL-10。此外，MSC减少了iNOS（+）M1巨噬细胞的数量，并恢复了CD 163（+）M2 macrophage.ConclusionsMultiple静脉输注的ADSCs产生了显着的保护作用，对长期的T2 DM并发症，减轻炎症和促进组织修复。目前的研究表明，脂肪干细胞可能是一种新的，替代细胞治疗长期糖尿病并发症。
BackgroundLong-term diabetes-associated complications are the major causes of morbidity and mortality in individuals with diabetes. These diabetic complications are closely linked to immune system activation along with chronic, non-resolving inflammation, but therapies to directly reverse these complications are still not available. Our previous study demonstrated that mesenchymal stem cells (MSCs) attenuated chronic inflammation in type 2 diabetes mellitus (T2DM), resulting in improved insulin sensitivity and islet function. Therefore, we speculated that MSCs might exert anti-inflammatory effects and promote the reversal of diabetes-induced kidney, liver, lung, heart, and lens diseases in T2DM rats.MethodsWe induced a long-term T2DM complication rat model by using a combination of a low dose of streptozotocin (STZ) with a high-fat diet (HFD) for 32 weeks. Adipose-derived mesenchymal stem cells (ADSCs) were systemically administered once a week for 24 weeks. Then, we investigated the role of ADSCs in modulating the progress of long-term diabetic complications.ResultsMultiple infusions of ADSCs attenuated chronic kidney disease (CKD), nonalcoholic steatohepatitis (NASH), lung fibrosis, and cataracts; improved cardiac function; and lowered serum lipid levels in T2DM rats. Moreover, the levels of inflammatory cytokines in the serum of each animal group revealed that ADSC infusions were able to not only inhibit pro-inflammatory cytokines IL-6, IL-1β, and TNF-α expression but also increase anti-inflammatory cytokine IL-10 systematically. Additionally, MSCs reduced the number of iNOS(+) M1 macrophages and restored the number of CD163(+) M2 macrophages.ConclusionsMultiple intravenous infusions of ADSCs produced significant protective effects against long-term T2DM complications by alleviating inflammation and promoting tissue repair. The present study suggests ADSCs may be a novel, alternative cell therapy for long-term diabetic complications.