Regenerative therapies in young hearts with structural or congenital heart disease

Ina Michel-Behnke, Imre Pavo, Sabine Recla, Markus Khalil, Christian Jux, Dietmar Schranz


Pediatric heart failure (HF) is rare. The prognosis is generally poor. HF is most frequently related to cardiomyopathy or congenital heart disease (CHD). Associated phenotypes are HF with preserved (HFpEF) or reduced ejection fraction (HFrEF); both in children with biventricular or univentricular circulation. Cardiac growth, differentiation, proliferation and consecutively regenerative and repair mechanisms are inversely related to the patient’s age; edaphic and circulating cardiac progenitor cells as well; in sum, there are enormous endogenous potentials repairing a diseased heart in particular in young children. Efforts supporting pediatric cardiac regeneration are clearly justified; cell-based therapies have been addressed in small series of children with end-stage HF of either the left or right ventricle, more recently in randomized clinical trials. Different cell populations like autologous bone marrow mononuclear cells, progenitor cells or cardiac derived cells have been injected into coronaries or directly into the myocardium. Beneficial at least transient improvement of cardiac function was observed in patients with dilative cardiomyopathy and CHD, mainly hypoplastic left heart syndrome (HLHS). Cellular repopulation and possibly more crucial, paracrine effects contributed in slowing down progression of pediatric end-stage HF. Our review summarizes the current knowledge in different scenarios of HF by cell-based cardiac therapies in critically ill children. Based on the actual clinical experience future work to distinguish responders from non-responders among other refinements will lead to individualized precision treatment of HF in children, what means a lot to a child on a long list waiting for heart transplantation (HTX).