title: Comparison of adipose tissue- and bone marrow- derived mesenchymal stem cells for alleviating doxorubicin-induced cardiac dysfunction in diabetic rats.
abstract: BACKGROUND
  Doxorubicin (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.
  
  
  METHODS
  Diabetes 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.
  
  
  RESULTS
  Glucose 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.
  
  
  CONCLUSIONS
  In 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.
authors: Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt. haniaammar@yahoo.com.
authors: Hania Ibrahim
authors: HI
authors: Ammar
authors: Regenerative Medicine Program, Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, R2H2A6, Canada. sequierg@myumanitoba.ca.
authors: Glen Lester
authors: GL
authors: Sequiera
authors: Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt. ursmortadella@yahoo.com.
authors: Mira B
authors: MB
authors: Nashed
authors: Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt. rashaammar@gmail.com.
authors: Rasha I
authors: RI
authors: Ammar
authors: Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt. halagabr@yahoo.com.
authors: Hala M
authors: HM
authors: Gabr
authors: Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt. drhanyelsebaee@hotmail.com.
authors: Hany E
authors: HE
authors: Elsayed
authors: Regenerative Medicine Program, Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, R2H2A6, Canada. sareenn@myumanitoba.ca.
authors: Niketa
authors: N
authors: Sareen
authors: Regenerative Medicine Program, Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, R2H2A6, Canada. abuelrue@myumanitoba.ca.
authors: Ejlal Abu-El
authors: EA
authors: Rub
authors: Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt. mahakaah2004@yahoo.com.
authors: Maha B
authors: MB
authors: Zickri
authors: Regenerative Medicine Program, Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, R2H2A6, Canada. sdhingra@sbrc.ca.
authors: Sanjiv
authors: S
authors: Dhingra
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006335:Heart Injuries / Q000139:chemically induced / Q000628:therapy*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004317:Doxorubicin