Microvessel co-transplantation improves poor remuscularization by hiPSC-cardiomyocytes in a complex disease model of myocardial infarction and type 2 diabetes.

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

People with type 2 diabetes (T2D) are at a higher risk for myocardial infarction (MI) than age-matched healthy individuals. Here, we studied cell-based cardiac regeneration post MI in T2D rats modeling the co-morbid conditions in patients with MI. We recapitulated the T2D hallmarks and clinical aspects of diabetic cardiomyopathy using high-fat diet and streptozotocin in athymic rats, which were then subjected to MI and intramyocardial implantation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with or without rat adipose-derived microvessels (MVs). hiPSC-CM alone engrafted poorly. Co-delivery of hiPSC-CMs with MVs yielded a smaller infarct area and a thicker left ventricle wall. Additionally, MVs robustly integrated into the infarcted hearts, improved the survival of hiPSC-CMs, and improved cardiac function. MV-conditioned media also promoted hiPSC-CM maturation in vitro, increasing cardiomyocyte (CM) size in an interleukin (IL)-6-dependent manner. Given the availability of MVs from human adipose tissue, MVs present great translational potential for the treatment of heart failure in people with T2D.

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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