Preconditioning diabetic mesenchymal stem cells with myogenic medium increases their ability to repair diabetic heart

Stem Cell Research & Therapy

Sheikh Riazuddin¹  Shaheen N Khan¹  Mahmood S Choudhery¹  Azra Mehmood¹  Shoaib Akhtar¹  Sadia Mohsin¹  Fatima Ali¹  Mohsin Khan¹ 

[1] National Center of Excellence in Molecular Biology, University of the Punjab, 87-West Canal Bank Road, Lahore, Pakistan

关键词: Oxidative stress;    Preconditioning;    Diabetic heart;    Mesenchymal stem cells;   

Others  :  847511
DOI  :  10.1186/scrt207

 received in 2012-11-22, accepted in 2013-05-16,  发布年份 2013

【 摘 要 】

Introduction

Mesenchymal stem cells (MSCs) have the potential for treatment of diabetic cardiomyopathy; however, the repair capability of MSCs declines with age and disease. MSCs from diabetic animals exhibit impaired survival, proliferation, and differentiation and therefore require a strategy to improve their function. The aim of the study was to develop a preconditioning strategy to augment the ability of MSCs from diabetes patients to repair the diabetic heart.

Methods

Diabetes was induced in C57BL/6 mice (6 to 8 weeks) with streptozotocin injections (55 mg/kg) for 5 consecutive days. MSCs isolated from diabetic animals were preconditioned with medium from cardiomyocytes exposed to oxidative stress and high glucose (HG/H-CCM).

Results

Gene expression of VEGF, ANG-1, GATA-4, NKx2.5 MEF2c, PCNA, and eNOS was upregulated after preconditioning with HG/H-CCM, as evidenced by reverse transcriptase/polymerase chain reaction (RT-PCR). Concurrently, increased AKT phosphorylation, proliferation, angiogenic ability, and reduced levels of apoptosis were observed in HG/H-CCM-preconditioned diabetic MSCs compared with nontreated controls. HG/H-CCM-preconditioned diabetic-mouse-derived MSCs (dmMSCs) were transplanted in diabetic animals and demonstrated increased homing concomitant with augmented heart function. Gene expression of angiogenic and cardiac markers was significantly upregulated in conjunction with paracrine factors (IGF-1, HGF, SDF-1, FGF-2) and, in addition, reduced fibrosis, apoptosis, and increased angiogenesis was observed in diabetic hearts 4 weeks after transplantation of preconditioned dmMSCs compared with hearts with nontreated diabetic MSCs.

Conclusions

Preconditioning with HG/H-CCM enhances survival, proliferation, and the angiogenic ability of dmMSCs, augmenting their ability to improve function in a diabetic heart.

【 授权许可】

   
2013 Khan et al.; licensee BioMed Central Ltd.

【 图 表 】

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