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Diabetic cardiomyopathy (DCM) is considered one of the main diabetic complications, contributing to specific forms of heart failure independent from hypertension or ischemia. There are increased research efforts to further explore a new potential therapeutic strategy for preventing or reversing DCM progression. The present research aimed to explore which type of stem cell-based therapies could serve as an effective tool for the treatment of DCM in type 1 diabetic rats. Four groups of male Wistar rats have been used in this study including the control group, a diabetic-untreated group, and two diabetic rat groups treated with either mesenchymal stem cells (MSCs) derived from adipose tissue (AD-MSCs) or bone marrow (BM-MSCs). Interestingly, serum levels of heart dysfunction markers (LDH and CK-MB) in the diabetic rats were found to be declined to near-normal levels following injection with either of the two MSCs types. Also, BM-MSCs or AD-MSCs (1×10 6 cell/rat)-treated diabetic rats exhibited significant decreases in the cardiac xanthine oxidase activity, reactive oxygen species, and malondialdehyde level, accompanied with marked elevations in various antioxidants, compared with the diabetic untreated group. The results also clearly point out the excellence of AD-MSCs injection as a potential agent in alleviating the DCM over BM-MSCs injection.

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Mesenchymal stem cells (MSCs) are considered to be a promising therapeutic protocol for diabetes mellitus (DM) management. The latter is attributed to their differentiation potentiality to pancreatic β-cells, angiogenesis, and immune-modulatory capabilities by releasing various paracrine factors. Interestingly, antioxidant co-administration increased the MSCs’ hypoglycemic and regenerative activities. Thus, this study aims to evaluate the therapeutic implication of type 1 DM after the co-administration of adipose tissue-derived-MSCs (AD-MSCs) and N,N′-d iphenyl-1,4-phenylenediamine (DPPD), compared to the single injection of either of them alone. In our four week long experiment, six rat groups were used as control, DPPD (250 mg/kg, i.p.), STZ-diabetic (D), D+DPPD, D+AD-MSCs (1 × 106 cell/rat, i.p.), and D+AD-MSCs+DPPD groups. Within this context, a single injection of AD-MSCs or DPPD into diabetic rats showed significant pancreatic anti-inflammatory, immunomodulation, antioxidant, and anti-apoptotic capacities, superior to AD-MSCs injection. However, AD-MSCs and DPPD co-administration into diabetic rats manifested the highest hypoglycemic and pancreatic regenerative activities in managing diabetes compared to the single shot of AD-MSCs or DPPD. These results highlight the synergetic role of DPPD as an antioxidant in enhancing AD-MSCs’ therapeutic applications.