CARDIAC PROGENITOR CELLS Flashcards
Introduction about the CPCs
They are tissue-specific progenitor cells related to the cardiac muscle
For a long time the general dogma was that the cardiac tissue couldn’t rely on any kind of progenitor but in 2009, it was demonstrated a minimal level of turn over
2003: first paper reporting a subpopulations of cells, c-kit+, high self renewal, clonogenic and able to differentiate into cardiomyocytes
In the following years: other subpopulations identified described as self renewing, multipotent (fibroblasts, epithelial cells and cardiomyocytes) and clonogenic
However, very low trans-differentiation potential but they can help the myocardium to recover from a injury
Doubts regarding the CPCs: origin, are they remnants of embryonic or circulating progenitors? Do they have a common progenitor?
What are the therapeutic approaches for which we can exploit the CPCs?
-cardiac cell therapy: ex-vivo isolation, expansion of the cells, transplantation in a pre-clinical mouse mode. Only cells still used are the cardiospheres and the cardiosphere-derived cells, main clinical trials, not effective and feasible
-in situ reactivation: stimulate the tissue-residing cells to activate them into their own niche with GFs and the secretome, reactivation of their embryonic plasticity and capacity in terms of proliferation, migration and acquisition of a specific commitment based on the assumption that they are not adult fibroblasts but they show some antigens related to cardiogenesis and embryonic development
EDPCs and cardiogenesis
Different contribution during cardiogenesis, in particular the role of the epicardium-derived progenitor cells
Identification of thymosin b4
Zebarafish as model of cardiac regeneration, in which the EDPCs can stimulate the cardiomyocytes to de-differentiate, enter the cell cycle and proliferate to regenerate the missing part within the tissue
Adult epicardium: unproliferative, quiescent, not mitotically active, loss of embryonic epicardial markers > restore their embryonic memory with the systemic administration of the thymosin b4 (not so efficient) > other strategies: direct reprogramming with the GMT combo
General consensus up today: no cells in the adult mammalian tissue can differentiate into cardiomyocytes with any kind of stimulation, unless we restore the embryonic gene expression profile
