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Article History

Received: 31 July 2023

Accepted: 2 April 2024

First Online: 24 April 2024

Declarations

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: Not applicable.

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: MD Griffin reports honoraria from the American Society of Nephrology; Théa Pharma Ltd., Ireland; and Novo Nordisk; research funding from Orbsen Therapeutics Ltd.; and advisory roles as an Editorial Board member for the journals Transplantation and Frontiers in Pharmacology and an Associate Editor for Mayo Clinic Proceedings. T O’Brien is co-editor-in-chief of Stem Cell Research and Therapy. For this manuscript, in keeping with Journal policy, he had no role in or visibility of the details of the review process. He is also a Director and Equity Holder in Orbsen Therapeutics. The other authors declare that they have no competing interests.

: What is already known about this subject?Diabetic cardiomyopathy (DCM) is a severe and common complication of prolonged diabetes mellitus and is associated with myocardial fibrosis.Mesenchymal stromal cells (MSCs) have been reported to improve cardiac fibrosis in experimental models of diabetes.Potential mechanisms of action of MSCs in diabetic complications include modulation of abnormal miRNA expression and suppression of pro-fibrotic inflammation.What is the key question?Does intravenous injection of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) reduce cardiac fibrosis in association with modulation of intra-myocardial microRNA (miRNA) expression following shorter and longer duration of diabetes?What are the new findings?1, Single intravenous injections of hUC-MSCs administered following 8 or 16 weeks of established diabetes reduced the severity of cardiac functional abnormalities and fibrosis detected 2 weeks later (10 and 18 weeks).2, At earlier and later time-points, diabetic cardiomyopathy was associated with decreased intra-cardiac expression of the anti-fibrotic miRNA-133a and concomitant increased expression of its target mRNA, COL1A1 and other markers of fibrosis. These abnormalities were potently reversed in diabetic animals that received hUC-MSC injection.3, Diabetes was also associated with evidence of systemic inflammation as well as increased intra-cardiac expression of some cytokines at both time-points. These abnormalities were more potently reversed by hUC-MSC injection at earlier compared to later time-point.How might this impact on clinical practice in the foreseeable future?Provide preclinical evidence for the clinical application of human umbilical cord mesenchymal stromal cells in the treatment of diabetes heart disease in the future.