Treatment with adipose tissue-derived mesenchymal stem cells exerts anti-diabetic effects, improves long-term complications, and attenuates inflammation in type 2 diabetic rats

Abstract

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.

Efficacy of mesenchymal stem cells in animal models of lupus nephritis: a meta-analysis

“…MSC are multipotent cells, and they have the capacity to self-renew and differentiate into the tissues of mesodermal origin [4,5]. They present immunomodulatory ability and are used as therapeutic agents for autoimmune disorders [4,6,7]. In clinical trials, the efficacy of MSC in the treatment of lupus nephritis is still controversial.…”

Encapsulation of Adipose-Derived Mesenchymal Stem Cells in Calcium Alginate Maintains Clonogenicity and Enhances their Secretory Profile

“…Furthermore, preclinical studies involving injection of ASCs into cardiac muscle in rats [ 53 , 54 ] and pig liver [ 55 ] reported no inflammatory reaction or fibrosis at the injection sites, and similar results were reported when ASCs were systemically injected: The cells were detectable in inflammatory tissues and appeared to play a role in reducing inflammation [ 56 , 57 ]. Nevertheless, in human medicine, it is very important to limit the risks of triggering an immune response.…”

Mesenchymal Stem Cells Transplantation in Diabetic Kidney Diseases: A Systematic Review and Meta-analysis

“…MSCs increased the expression of antiin ammatory gene, promoted the proliferation of monocytes and transference into M2 phenotype by activating the expression of cytokines like IL-10, IGF-1 and VEGF [39]. Not only elevating arginase 1 (Arg1), the markers of M2 macrophages, MSCs also reduced M1 level [31,33]. MSCs could restore Mφ autophagy and mitochondria bioenergetics in DN mice, alter Mφ into the M2 phenotype via TFEBmediated autophagy and thereby inhibit in ammatory response [40].…”

“…ADSCs could inhibit the expression of pro-in ammatory cytokines such as IL-1β, IL-6 and TNF-α, and systematically increase the expression of anti-in ammatory cytokines IL-10 as well [18,33]. The epithelium-mesenchymal transdifferentiation (EMT) of podocyte in DN was considered associated with stromal interaction molecule (STIM) mediated by FcγRII.…”

“…The dosage and administration of MSCs therapy vary greatly. Multiple intravenous infusion of ADSCs could attenuate in ammation, promote tissue repair and improve the prognosis of the long-term complications of T2DM [33]. Compared with intravenous injection, ADSCs sheet transplantation to the kidney had the advantage of higher e ciency [32].…”