Innovative prevascularization model for improving transplantation of human stem cell derived cardiomyocytes

Myocardial infarction (MI) is one of the most prevalent types of cardiac diseases, representing a significant burden for the health care system. A potential cure for patients with MI lies in cell-based therapies where stem... [ view full abstract ]

Myocardial infarction (MI) is one of the most prevalent types of cardiac diseases, representing a significant burden for the health care system. A potential cure for patients with MI lies in cell-based therapies where stem cell-derived cardiomyocytes (SC-CMs) can be transplanted to the MI area to replace the cardiomyocytes lost during MI. However, these therapies yield only modest improvements in cardiac function due to massive death of implanted cells. Most cell death occurs in the first few days post-transplantation due to ischemia. Different strategies have been pursued to promote blood perfusion in cardiac grafts, such as co-implantation of endothelial cells and/or addition of angiogenic factors. The drawback of these approaches is the long time required for new vessels to form and to carry blood (~ 1 week) compared to the rapid death of transplanted CMs (2-3 days), highlighting the need for effective alternative approaches.
We developed an innovative strategy for generating functional vascularized myocardium that relies of the use of ready-made microvessels that are able to form a competent vasculature when implanted and have, connect with the host vessels and carry blood within the first days post implantation. Our preliminary data demonstrated that co-implantation of SC-CMs and microvessels significantly improves survival of subcutaneous implanted SC-CM in Rag1 mice. Our ongoing studies focus on the generation of pre-vascularized cardiac tissues composed of microvessels and SC-CMs to improve the survival and retention of transplanted CMs post MI.