Cardio Repair European Multidisciplinary Initiative.
Ischemic Heart Disease (IHD) is the biggest single cause of death in Europe and in the developed world. Angioplasty and stents are successful in re-establishing perfusion of ischemic myocardium and have helped to reduce early mortality after Acute Myocardial Infarction (AMI). However damaged tissue is not recovered and, therefore, this is always followed by cardiac remodeling and Chronic Heart Failure (CHF). CHF is a terminal disease with an annual mortality rate of approximately 18% with no cure besides heart transplantation, only available to a minority of patients. Autologous cell therapy has been proposed as a solution and clinically tested but has proven marginally effective at best. Its cost and the complexity of clinical procedures make it unsuitable for treating the large number of patients that need affordable and readily available products to treat the acute phase of the disease. Moreover, most of these approaches are predicated on the outmoded concept that the adult human myocardium lacks regenerative capacity. Recent findings show that adult myocardium harbours a population of resident pluripotent cells with the characteristics of true Cardiac Stem Cells (CSC) able to regenerate contractile myocardium. This opens novel therapeutic avenues capable of producing real anatomical and functional regeneration. The CARE-MI project addresses the clinical implementation of this recent paradigmatic change. We are clinically testing and developing myocardial regenerative therapies based on the in situ activation, multiplication and differentiation of the endogenous CSCs
The main objective of the CARE-MI project is to develop broadly available and clinically applicable treatments for ischemic heart disease (IHD) by exploiting the biology of endogenous resident cardiac stem cells (eCSC) and the molecular mechanisms responsible for their activation and differentiation in situ. The proposed therapies act directly on the resident eCSCs resulting in their activation and differentiation into cardiac myocytes, endothelial and smooth muscle vascular cells to regenerate the contractile tissue and the microvasculature lost as a result of the ischemic event. These therapies are based on and have been validated through solid preclinical results in animal models which are relevant to human cardiac anatomy, physiology and pathology. These approaches, if properly developed, have the potential to fulfil all the requirements for an effective clinically broadly applicable myocardial regenerative therapy outlined above. To accomplish this goal it will be necessary to compare the relative merits of the two therapies proposed, their relative potential as therapies for broad clinical application to activate the endogenous regenerative capacity of the myocardium before we will be able to address whether their combined use offers any additional benefits.
In addition to these main goals, the project will include the comprehensive development of basic and clinical enabling technologies needed to assure the success and the further development of the approaches proposed. The following specific aims will also be accomplished:
Establish the molecular/genetic pathways regulating endogenous cellular regeneration in the myocardium.
Identify the key regenerative agents that activate the endogenous regenerative process.
Elucidate the optimal time of administration and dosage of the regenerative agents.
Generate the molecular biology tools required for advancing the knowledge of the regenerative process.
Test different formulations with biodegradable polymers for the safe intravascular local delivery of the regenerative agents.
Establish solid animal experimental models for rigorous preclinical testing, including randomized assays.
Optimise imaging techniques for the non-invasive monitoring of the delivery and fate of the regenerative agents as well as the evolution of the regenerative response with particular emphasis on the immunological response, myocardial regional contractility, degree of perfusion and metabolism of the regenerating zone.
Perfect the clinical grade production processes of CSCs and encapsulated growth factors required for preclinical and human trials of allogeneic cells and recombinant factors.
EC 7° Framework Programme - HEALTH-2009-1.4-3
BMI Laboratory is involved in this project as subcontractor of the University of Ljubljana
CARE-MI project will last 60 months, from 01/04/2010 to 31/03/2015