Abstract
Introduction: Cardiovascular disease (CVD) is a type of disease that affects the function of cardiac-vascular tissues. This study aimed to consider the possible effects of autophagy, as an intrinsic catabolic pathway of cells, on the differentiation and aging process of mesenchymal stem cells (MSCs). Methods: In this study, bone marrow-derived MSCs were obtained from rabbit bone marrow aspirates. The stemness feature was confirmed by using flow cytometry analysis Cells at passage three were treated with 50 μM Metformin and 15μM hydroxychloroquine (HCQ) for 72 hours. The intracellular accumulation of autophagolysosomes was imaged using LysoTracker staining. Protein levels of autophagy (LC3II/I ratio), aging (Klotho, PARP-1, and Sirt-1) effectors, and cardiomyocyte-like phenotype (α-actinin) were studied by western blotting. Results: Based on our findings, flow cytometry analysis showed that the obtained cells expressed CD44 and CD133 strongly, and CD31 and CD34 dimly, showing a typical characteristic of MSCs. Our data confirmed an increased LC3II/I ratio in the metformin-received group compared to the untreated and HCQ-treated cells (P < 0.05). Besides, we showed that the incubation of rabbit MSCs with HCQ increased cellular aging by induction of PARP-1 while Metformin increased rejuvenating factor Sirt-1 comparing with the normal group (P < 0.05). Western blotting data showed that the autophagy stimulation response in rabbit MSCs postponed the biological aging and decreased the differentiation potential to the cardiac cells by diminishing α-actinin comparing with control cells (P < 0.05). Conclusion: In summary, for the informants in this study, it could be noted that autophagy inhibition/stimulation could alter rabbit MSCs aging and differentiation capacity.
Highlights
Cardiovascular disease (CVD) is a type of disease that affects the function of cardiacvascular tissues
Morphological changes Monitoring morphology of rabbit mesenchymal stem cells (MSCs) after treatment with Met and HCQ showed that autophagy modulation could change the cell shape (Figure 2B)
Based on our observations, in another general note, we can state that the stimulation of autophagy by 50 μmol Met, by modulating Klotho, PARP-1 and Sirt-1, has the potential to differentiate rabbit mesenchymal stem cells
Summary
Cardiovascular disease (CVD) is a type of disease that affects the function of cardiacvascular tissues. Many efforts have been placed to develop new therapeutic strategies.[1, 2] Despite tremendous progress In AMI management, many people with CVD still develop chronic heart failure (CHF).[3] Because of the complexities of existing approaches such as their after effects, deficiencies, and problems, there are many substitute approaches accessible such as drug administration, heart transplantation, and intra/ extra cardiac devices to recover the quality of patient’s lifestyle In most cases, these approaches are not efficient enough to restore the normal function of infarcted hearts. It has been well-documented that the regenerative capability of different stem progenitors decreases by aging.[8,9] Many factors and signaling pathways could decrease/increase the aging process in stem cells.[9, 10] The autophagy, along with ubiquitin-proteasome system, are believed to be the two main pathways for degradation gmail.com
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