Rebuilding the heart with human pluripotent stem cells.
PhD Supervisors: Prof Chris Denning, Dr Alexander Kondrashov, and Profs. Sian Harding and Molly Stevens, Imperial College London.
The limited regenerative potential of the heart means that once it experiences a major trauma (e.g. myocardial infarction), complete recovery is unlikely. Indeed, 20 million people a year die due to heart attacks. This has prompted numerous clinical trials whereby stem cell populations, derived from skeletal muscle or bone marrow, are transplanted into the damaged heart. However, in truth, there is virtually no clinical improvement in these patients because the transplanted cells do not generate new heart cells and the host myocardium is not restored. A complete rethink is needed.
In contrast to skeletal and bone marrow stem cells, human pluripotent stem cells (hPSCs) offer a new and potentially unlimited source of cardiomyocytes [1,2,3]. Initial attempts to simply inject hPSC-cardiomyocytes into the heart were unsuccessful because the cells leaked out, died or failed to fully integrate functionally. Much smarter and well thought-out second generation systems for cell delivery are now being developed, whereby hPSC-cardiomyocytes are integrated into different materials as tissue engineered constructs. This includes cell sheets, cardiac patches and engineered heart tissue [4,5].
Ongoing collaboration via a British Heart Foundation Programme Grant between Denning and Kondrashov (Nottingham) and Harding (Imperial College London) is using hPSC-cardiomyocytes to better understand the function of the heart. Moreover, a major high profile £4.6m BHF-funded international consortium involving these researchers coupled with an exception grouping of scientists (e.g. Profs. Molly Stevens, Imperial;Thomas Eschenhagen, Germany; Marc Mercola, USA), now seeks to develop scalable populations of hPSC-cardiomyocytes that can be integrated into tissue engineered constructs. Ultimately, the ability of these constructs to improve heart function will be tested ex vivo in cardiac tissue slices and in vivo in animal models of heart failure.
