A Collagen Cardiac Patch Incorporating Alginate Microparticles Permits the Controlled Release of HGF and IGF-1 to Enhance Cardiac Stem Cell Migration and Proliferation

A major weakness in existing therapies for myocardial infarction is their inability to regenerate the resulting damaged cardiac muscle. Thus, the goal of current experimental strategies is finding the means for attenuation of the progressive processes leading to tissue destruction, while inducing myocardial tissue regeneration (1, 2).Regenerative cardiology’s Holy Grail has been the development of procedures to either replace lost myocytes with transplanted stem cells or to use stem cells to mediate functional repair through paracrine effects (3-6).

The most primitive undifferentiated population of stem cells in the heart, the c-KitPOS Cardiac Stem Cell (CSC) pool which was the first stem cell identified in the rat heart and, up to date, this CSC pool is still the most extensively characterised (7, 8). CSCs are a heterogenic group of cells and they are concentrated in specific areas of the heart, such as the atria or pericardium (9). They represent a logical source to exploit in myocardial regeneration because of their likelihood to be intrinsically programmed to generate viable cardiac tissues in vitro and increase its viability in vivo (10-13).

The ideal replacement for the lost myocardium after myocardial infarction is functional autologous myocardial tissue, which can bypass issues around immunosuppression associated with allogenic therapies (14). However, as presently practiced, the isolation and expansion of endogenous cardiac stem cells (eCSCs) for autologous cell transplantation is slow and expensive. In addition, endomyocardial biopsies are difficult to attain (12, 15). Thus, there is need for strategies to specifically activate in situ the intrinsic cardiac regenerative potential represented by the eCSCs using combinations of growth factors, cytokines and drugs, obviating the need for cell transplantation (15, 16).

As presently practiced, the isolation and expansion of CSCs for autologous cell transplantation is slow, expensive and difficult to attain. Thus, there is need for strategies to specifically activate in situ the intrinsic cardiac regenerative potential represented by the CSCs using combinations of growth factors obviating the need for cell transplantation. By favouring the natural regenerative capability of CSCs, it is hypothesised that the cardiac patch presented here will result in positive therapeutic outcomes in myocardial infarction and heart failure patients in the future.