New insights into paracrine mechanisms of human cardiac progenitor cells.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Maxeiner
Hagen
H
Department of Anaesthesiology, University Hospital Giessen and Marburg, Campus Giessen, Rudolf-Buchheim-Str 7, 35392 Giessen, Germany.
Krehbiehl
Nina
N
Müller
Andrea
A
Woitasky
Nadine
N
Akintürk
Hakan
H
Müller
Matthias
M
Weigand
Markus A
MA
Abdallah
Yaser
Y
Kasseckert
Sascha
S
Schreckenberg
Rolf
R
Schlüter
Klaus-Dieter
KD
Wenzel
Sibylle
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D019899:Paracrine Communication / Q000502:physiology*; D051381:Rats; D013234:Stem Cells / Q000502:physiology*; D055815:Young Adult
D017077:Culture Media, Conditioned; D016207:Cytokines