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.

Background and ObjectivesAmiodarone (AM), a class 3 antiarrhythmic drug, has been associated with variety of adverse effects, the most serious of which is pulmonary toxicity. Ator (A) is a statin, known for their immunomodulatory and anti-inflammatory activities. Recent studies provide evidence of potential therapeutic effect of statins on lung injury. Adipose derived stem cells (ADSCs) have shown great promise in the repair of various tissues. The present study aimed at investigating and comparing the possible therapeutic effect of A and ADSCs on AM induced lung injury in albino rats.Methods and Results34 adult male albino rats were divided into 5 groups: control group (Gp I), A group (Gp II) received 10 mg/kg of A orally 6 days (d)/week (w) for 4 weeks (ws), AM group (Gp III) received 30 mg/kg of AM orally 6 d/w for 4 ws, AM&A group (Gp IV) received AM for 4ws then A for other 4 ws and AM&SCs group (Gp V) received AM for 4 ws then injected with 0.5 ml ADSCs on 2 successive days intravenously (IV). Histological, histochemical, immunohistochemical and morphometric studies were performed. Group III displayed bronchiolitis obliterans, thickened interalveolar septa (IAS) and thickened vascular wall which were proven morphometrically. Increased area% of collagen fibers and apoptotic changes were recorded. All findings regressed on A administration and ADSCs therapy.ConclusionAtor proved a definite ameliorating effect on the degenerative, inflammatory, apoptotic and fibrotic changes induced by AM. ADSCs administration denoted more remarkable therapeutic effect compared to A.

Background and Objectives:The fibrosing form of lung injury (occupational, environmental, infective or drug induced) is associated with significant morbidity and mortality. Amiodarone (AM), often prescribed for control of arrhythmias is considered a potential cause. No effective treatment was confirmed, except lung transplantation. Intravenous (IV) stem cell therapy may produce pulmonary emboli or infarctions. Despite being commonly used in clinical practice, the intraperitoneal (IP.) route has been rarely used for cell delivery. The present study aimed at investigating and comparing the possible effect of IP stem cell therapy (SCT) on pulmonary toxicity versus the intravenous route in a rat model of amiodarone induced lung damage.Methods and Results:36 adult male albino rats were divided into 4 groups. Rats of AM group were given 30 mg/kg daily orally for 4 weeks. Rats of IV SCT group were injected with stem cells in the tail vein. Rats of IP SCT group received IP cell therapy. Histological, histochemical, immunohistochemical and morphometric studies were performed. Obstructed bronchioles, overdistended alveoli, reduced type I pneumocytes, increased thickness of alveolar septa and vessels wall besides increased area% of collagen fibers regressed in response to IV and IP SCT. The improvement was more obvious in IV group. The area% of Prussion blue +ve and CD105 +ve cells was significantly higher in IV group.Conclusions:Cord blood MSC therapy proved definite amelioration of lung injury ending in fibrosis. The effect of IP SCT was slightly inferior to that of IV SCT, which may be overwhelmed by repeated IP injection.

Background:Severe injuries in skeletal muscle result in muscle weakness that delays recovery and contribute to progressive decline in muscle function. Microcurrent therapy (MCT) is a novel treatment method used in soft tissue injury and tissue regeneration therapy. The regenerative capacity of skeletal muscle tissue resides in satellite cells, the quiescent adult stem cells.Aim:The present work aimed at investigating the relation between microcurrent therapy and local stem cells in regeneration of induced skeletal muscle injury in albino rat.Materials and methods:Twenty six adult male albino rats were divided into Sham group, Injury group (I): subjected to soleus muscle injury and subdivided into subgroups I1 & I2 sacrificed 2 and 4 weeks after injury respectively. Microcurrent group (M): subjected to muscle injury and micro-current was applied. The animals were subdivided into subgroups M1 and M2 sacrificed 2 and 4 weeks after injury. Histological, immunohistochemical and morphometric studies were performed.Results:Atypical fibers widely separated by infiltrating cells and strong acidophilic sarcoplasm with focal vacuolations were found in injury group. In M1 subgroup few atypical fibers were found. In M2 subgroup multiple typical fibers were detected. A significant decrease in the mean area of atypical fibers, a significant increase in the mean area% of alpha SMA+ve cells and that of CD34+ve cells were found in microcurrent group compared to injury group. Conclusion: A definite therapeutic effect of the microcurrent was found on induced skeletal muscle injury. This effect was proved to be related to satellite cell activation.

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