Comparison of adipose tissue- and bone marrow- derived mesenchymal stem cells for alleviating doxorubicin-induced cardiac dysfunction in diabetic rats

Abstract

IntroductionDoxorubicin (DOX) is a well-known anticancer drug. However its clinical use has been limited due to cardiotoxic effects. One of the major concerns with DOX therapy is its toxicity in patients who are frail, particularly diabetics. Several studies suggest that mesenchymal stem cells (MSCs) have the potential to restore cardiac function after DOX-induced injury. However, limited data are available on the effects of MSC therapy on DOX-induced cardiac dysfunction in diabetics. Our objective was to test the efficacy of bone marrow-derived (BM-MSCs) and adipose-derived MSCs (AT-MSCs) from age-matched humans in a non-immune compromised rat model.MethodsDiabetes mellitus was induced in rats by streptozotocin injection (STZ, 65 mg/kg b.w, i.p.). Diabetic rats were treated with DOX (doxorubicin hydrochloride, 2.5 mg/kg b.w, i.p) 3 times/wk for 2 weeks (DOX group); or with DOX+ GFP labelled BM-MSCs (2x106cells, i.v.) or with DOX + GFP labelled AT-MSCs (2x106cells, i.v.). Echocardiography and Langendorff perfusion analyses were carried out to determine the heart function. Immunostaining and western blot analysis of the heart tissue was carried out for CD31 and to assess inflammation and fibrosis. Statistical analysis was carried out using SPSS and data are expressed as mean ± SD.ResultsGlucose levels in the STZ treated groups were significantly greater than control group. After 4 weeks of intravenous injection, the presence of injected MSCs in the heart was confirmed through fluorescent microscopy and real time PCR for ALU transcripts. Both BM-MSCs and AT-MSCs injection prevented DOX-induced deterioration of %FS, LVDP, dp/dt max and rate pressure product. Staining for CD31 showed a significant increase in the number of capillaries in BM-MSCs and AT-MSCs treated animals in comparison to DOX treated group. Assessment of the inflammation and fibrosis revealed a marked reduction in the DOX-induced increase in immune cell infiltration, collagen deposition and αSMA in the BM-MSCs and AT-MSCs groups.ConclusionsIn conclusion BM-MSCs and AT-MSCs were equally effective in mitigating DOX-induced cardiac damage by promoting angiogenesis, decreasing the infiltration of immune cells and collagen deposition.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0142-x) contains supplementary material, which is available to authorized users.

Adipose derived stem cell transplantation is better than bone marrow mesenchymal stem cell transplantation in treating hindlimb ischemia in mice

“…However, BMMSCs may represent a better choice for treating bone disorders (Lotfy et al, 2014). Liao et al have reviewed and compared the bone formation between AD-MSCs and BM-MSCs and showed that there are no significant differences between these two kinds of stem cells (Liao and Chen, 2014 (Ammar et al, 2015). In another study, Hiwatashi et al compared the effects of BM-MSCs and AD-MSCs in combination with atelocollagen for vocal fold scar regeneration.…”

“…Stem cell therapy is promising because it enables the creation of new blood vessels that supply oxygen and nutrients to the ischemic area. Both bone marrow derived mesenchymal stem cells (BM-MSCs) and adipose derived mesenchymal stem cells (AD-MSCs) can be obtained from preclinical (Liu et al, 2015;Yoshida et al, 2016) and clinical applications (Ammar et al, 2015;Peeters Weem et al, 2016) to treat ALI. Some studies have used other kinds of stem cells in preclinical trials, including menstrual blood cells (Vu et al, 2015), umbilical cord blood derived endothelial progenitor cells , placenta derived MSCs (Xie et al, 2016;Zhang et al, 2014), and Wharton's jelly derived endothelial progenitor cells (Shen et al, 2013).…”

Combined treatment with systemic resveratrol and resveratrol preconditioned mesenchymal stem cells, maximizes antifibrotic action in diabetic cardiomyopathy

“…Data from literatures have highlighted a potential regenerative role for mesenchymal stem cells (MSCs) in cardiac diseases (Natsumeda et al, ). In the context of DM we and others have reported that MSCs can ameliorate cardiac dysfunction, exert antiapoptotic, angiogenic effects, and most importantly attenuate fibrosis and remodeling (Ammar et al, ; Q. Li, Turdi, Thomas, Zhou, & Ren, ; Van Linthout et al, ; N. Zhang, Li, Luo, Jiang, & Wang, ). Independent on MSCs differentiation, models of myocardial infarction (MI), elucidated that MSCs can improve function by secreting different antiapoptotic, antifibrotic, and angiogenic paracrine factors (H. Li et al, ; Song et al, ).…”

Comparative proteomic analysis of extracellular vesicles isolated from porcine adipose tissue-derived mesenchymal stem/stromal cells

“…One particularly attractive application is in cardiovascular disease, the leading cause of mortality in countries with developed and emerging economies3. Indeed, a progressively increasing number of studies has focused on the ability of MSCs to repair the damaged myocardium in murine models of hypertension and heart failure45. Furthermore, in recent years, we and others have tested the efficacy of MSCs for attenuating cardiac and renal injury in large animal models of cardiovascular disease6.…”