New insights into paracrine mechanisms of human cardiac progenitor cells

Hagen Maxeiner, University Hospital Giessen and Marburg, Germany
Nina Krehbiehl, Justus Liebig University, Giessen
Andrea Müller, Justus Liebig University, Giessen
Nadine Woitasky, Justus Liebig University, Giessen
Hakan Akintürk, University Hospital Giessen and Marburg, Germany
Matthias Müller, University Hospital Giessen and Marburg, Germany
Markus A. Weigand, University Hospital Giessen and Marburg, Germany
Yaser Abdallah, Aga Khan University
Sascha Kasseckert, Justus Liebig University, Giessen
Rolf Schreckenberg, Justus Liebig University, Giessen

This work was published before the author joined Aga Khan University.

Abstract

Aims Cardiac progenitor cells (CPCs) have been shown to promote cardiac regeneration in vivo. Understanding the function of CPCs is essential for further implementation of these cells in the treatment of cardiac diseases. The present study tested the hypothesis that adult CPC exert paracrine effects that lead to an improvement in the functional characteristics of cardiomyocytes. This study also investigated whether aging (we included patients aged between 4 months and 81 years) has any effect on the paracrine mechanisms of CPC.

Methods and results The supernatant of CPC generated both from human and rat hearts—so called ‘conditioned cardiosphere medium’ improved the contractile behaviour of isolated adult cardiomyocytes in a concentration‐dependent manner after incubation for 24 h and increased the SERCA/NCX ratio. The observed positive effects on contractile behaviour were independent of the CPC donors' age. Conditioned cardiosphere media also normalized angiotensin II‐induced contractile dysfunction. Cytokines released by CPC into the media were detected by cytokine arrays.

Conclusion The observed diversity of cytokines released by CPC needs to be further elucidated in detail. Nevertheless, CPC are a promising therapeutic approach in the field of cardiac disease. The methods described allow investigation of the underlying paracrine mechanisms in a standardized in vitro situation.