BHF funded project “The Distribution and Characteristics of Endogenous Cardiac Stem Cells in the Adult Human Heart” in collaboration with Prof Harding, Georgina Ellison (Kings College), Prof Sir Magdi Yacoub (Harefield), Prof Nagy Habib (IC – Hepatobiliary) and others was a logical evaluation of Endogenous Cardiac stem cells in all four chambers in normal and abnormal heart to potentially identify the source/treatment chamber for expansion of eCSCs and harvest exosomes.
The next BHF project “The Identification and Characteristics of Specific Human Cardiac Fibroblasts leading to Myocardial Regeneration in the Adult Human Heart”, helped to improve the understanding of cardiac fibroblasts and possibly target fibroblasts as the treatment cell.
Both the above projects led to a natural progression to explore our current evaluation of paracrine and exosome therapies.
Paracrine (Exosome) therapy is being validated as a primary functional mechanism for efficacy in animal models has with encouraging endeavours in Phase 1 human chronic heart failure trials. The main question is to determine how its implementation could be extended to common clinical practice.
To fill this gap, it is critical to first validate the hypothesis that the grafted stem cells primarily act by harnessing endogenous repair pathways.
Indeed, the beneficial effect of the administration of mesenchymal stem cell-derived micro vesicles has already been established in an animal model of myocardial ischaemia.
The paracrine hypothesis, if it was unequivocally validated, has major practical consequences which could really allow a dramatic improvement in the efficacy of cardiac cell therapy and allow it to fill the gap which still exists between well-controlled trials and a large-scale clinical use. Collaboration with Sian Harding and Costanza Emmanuelli has been a fruitful step in the right direction
One important consequence of such an approach could be to make it accessible to a larger number of patients suffering from heart failure who have exhausted conventional therapies and are therefore in need of new therapeutic options or in combination with established surgical treatment.
Importantly, discussions regarding effective engraftment with multiple small postage stamp patches dissected onto the failing myocardium evaluated with high resolution MRI are already in advanced phases of implementation with expected collaborations with Sian Harding, Magdi Yacoub (Harefield) Costanza Emmanuelli, Pilar Ruiz-Lozano (Regencor), Sean Davidson (UCL), Raimondo Ascione (Bristol), Molly Stevens, Mauro Giacca (Trieste / Kings College), Georgina Ellison (Kings College) Phillippe Menasche (France) and importantly specific collaboration with Prof Harding will allow comparison with iPS and MS cells. Pilot studies are already underway in collaboration with Prof Harding and Prof Emmanuelli for submission of funding application to the BHF.
Effect of Secretory and Paracrine factors on Myocardial Regeneration in patients with Chronic Heart Failure - (ESPA - MOREHF) – Clinical Trial – Protocol writing stage
Infective Endocarditis of Mitral Valve, European Association of Cardiothoracic Surgery, 2007
Mitral Valve Repair, EACTS, 2006
Hammersmith Echo Course, Hammersmith Hospital