Background: Diabetic cardiomyopathy (DCM) is a common condition that is associated with morbidity and mortality. With
the medical advancement in cell treatment, stem cell therapy has a potential therapeutic strategy for DCM.
Objectives: We aim to evaluate the possible therapeutic effects of Mesenchymal stem cells (MSCs) versus melatonin (MLT)
preconditioned-MSCs in induced diabetic cardiomyopathy in rats.
Materials and Methods: Forty-five male adult albino rats were divided into four groups. Group I: Control group. Group < br />II: Diabetic group: Rats received single intraperitoneal injection of streptozotocin STZ (50 mg/kg body weight). Group < br />III: DC treated with MSCs. Group IV: DC treated with MLT preconditioned-MSCs. Histological, ultrastructural and
immunohistochemical studies were performed on left ventricle myocardium. We also estimated the survival of MLTpreconditioned
MSCs in vitro. Bcl-2, Casp-3, interleukin 1 (IL-1), and interleukin 10 (IL-10) expression were measured using
real-time PCR in tissue homogenates.
Results: Our findings revealed a significant increase in immunohistochemical expression of apoptotic markers in the diabetic
group, as well as a disruption of the normal cardiac histological ultrastructure. Melatonin improved MSCs survival in vitro
and altered apoptotic markers. In addition, the melatonin-preconditioned MSC group showed a significant increase in B-cell
lymphoma 2 (Bcl-2) mRNA expression and a significant decrease in Casp-3. Enhanced immunomodulatory behavior was
obvious by a significant attrition of the mRNA expression of IL-1β (inflammatory-agonist) and a significant altitude of IL-10
(inflammatory-antagonist).
Conclusion: The melatonin-preconditioning of MSCs enhance their survival and immunomodulatory activities and precisely
restored cardiac histology. Thus, it unveils an encouraging interference of DC.