Preclinical Evidence for the Effectiveness of Mesenchymal Stromal Cells for Diabetic Cardiomyopathy: A Systematic Review and Meta-analysis

Background: Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus that endangers human health. DCM results in cardiac dysfunction, which eventually progresses to heart failure. Mesenchymal stromal cells (MSCs), a type of multipotent stem cell, have shown promising therapeutic effects in various cardiovascular diseases and diabetic complications in preclinical studies due to their immunomodulatory and regenerative abilities. However, there is still a lack of evidence to summarize the effectiveness of MSCs in the treatment of DCM. Therefore, a meta-analysis and systematic review are warranted to evaluate the therapeutic potential of MSCs for DCM in preclinical studies.Methods: A comprehensive literature search in English or Chinese was conducted in PubMed, EMBASE, web of Science, Cochrane Library, and China National Knowledge Internet from inception to June 30, 2022. The summarized outcomes included echocardiography, morphology, and pathology. Data were independently extracted and analyzed by two authors. The software we adopted was Review Manager5.4.1. This systematic review was written in compliance with PRISMA 2020 and the review protocol was registered on PROSPERO, registration no. CRD42022350032.<br />Results: We included 20 studies in our meta-analysis to examine the efficacy of MSCs in the treatment of DCM. The MSC-treated group showed a statistically significant effect on left ventricular ejection fraction (WMD=12.61, 95% CI 4.32 to 20.90, P=0.003) and short axis fractional shortening (WMD=6.84, 95% CI 4.09 to 9.59, P < 0.00001). The overall effects on the ratio of early to late diastolic mitral annular velocity, left ventricular end-diastolic pressure, maximum positive pressure development, maximum negative pressure development, left ventricular relaxation time constant, heart weight to body weight ratio, fibrosis area, and arteriole density were analyzed, suggesting that MSCs represent an effective therapy for the treatment of DCM.<br />Conclusion: Our results suggest a therapeutic role for MSCs in the treatment of DCM, and these results provide support for the use of MSCs in clinical trials of patients with DCM.