Enhancement strategy for effective vascular regeneration following myocardial infarction through a dual stem cell approach

Abstract

Heart attack: Stem cells team up to fix blood vessels A treatment involving two different types of stem cells leads to repairing failed hearts by making new functional blood vessels. Researchers at the City University of Hong Kong and the Catholic University of Korea induced heart attacks in rats before injecting the hearts with endothelial cells derived from human induced pluripotent stem cells, specialized to form blood vessels. These cells successfully induced the formation of new blood vessels in the damaged hearts. The researchers combined this treatment with a cardiac patch containing engineered human adult stem cells, which improved the survival and performance of the endothelial cells. And this dual stem cell treatment resulted in enhanced cardiac function and a higher number of larger and stronger new blood vessels than those produced by the single-cell treatment suggesting an effective way to repair failed hearts. Since an impaired coronary blood supply following myocardial infarction (MI) negatively affects heart function, therapeutic neovascularization is considered one of the major therapeutic strategies for cell-based cardiac repair. Here, to more effectively achieve therapeutic neovascularization in ischemic hearts, we developed a dual stem cell approach for effective vascular regeneration by utilizing two distinct types of stem cells, CD31(+)-endothelial cells derived from human induced pluripotent stem cells (hiPSC-ECs) and engineered human mesenchymal stem cells that continuously secrete stromal derived factor-1 alpha (SDF-eMSCs), to simultaneously promote natal vasculogenesis and angiogenesis, two core mechanisms of neovascularization. To induce more comprehensive vascular regeneration, we intramyocardially injected hiPSC-ECs to produce de novo vessels, possibly via vasculogenesis, and a 3D cardiac patch encapsulating SDF-eMSCs (SDF-eMSC-PA) to enhance angiogenesis through prolonged secretion of paracrine factors, including SDF-1 alpha, was implanted into the epicardium of ischemic hearts. We verified that hiPSC-ECs directly contribute to de novo vessel formation in ischemic hearts, resulting in enhanced cardiac function. In addition, the concomitant implantation of SDF1 alpha-eMSC-PAs substantially improved the survival, retention, and vasculogenic potential of hiPSC-ECs, ultimately achieving more comprehensive neovascularization in the MI hearts. Of note, the newly formed vessels through the dual stem cell approach were significantly larger and more functional than those formed by hiPSC-ECs alone. In conclusion, these results provide compelling evidence that our strategy for effective vascular regeneration can be an effective means to treat ischemic heart disease.