Background/Objectives Epicardium-derived progenitor cells (EPDCs) differentiate into all heart cell types in the embryonic heart, yet their differentiation into cardiomyocytes in the adult heart is limited and poorly described. This may be due to EPDCs lacking myogenic potential or the inert adult heart missing regenerative signals essential for directed differentiation of EPDCs. Herein, we aimed to evaluate the myogenic potential of neonatal EPDCs in adult and neonatal mouse myocardium, as well as in skeletal muscle. The two latter tissues have an intrinsic capability to develop and regenerate, in contrast to the adult heart. Methods Highly purified mouse EPDCs were transplanted into damaged neonatal and adult myocardium as well as regenerating skeletal muscle. Co-cultures with skeletal myoblasts were used to distinguish fusion independent myogenic conversion. Results No donor EPDC-derived cardiomyocytes were observed in hearts. In contrast, a remarkable contribution of EPDCs to skeletal muscle myofiber formation was evident in vivo. Furthermore, co-cultures of EPDCs with myoblasts showed that EPDCs became part of multinucleated fibers and appeared to acquire myogenic traits independent of a fusion event. Fluorescence activated cell sorting of EPDCs co-cultured with and without myoblasts and subsequent qRT-PCR of 64 transcripts established that the myogenic phenotype conversion was accomplished through induction of a transcriptional myogenic program. Conclusion These results suggest that EPDCs may be more myogenic than previously anticipated. But, the heart may lack factors for induction of myogenesis of EPDCs, a scenario that should be taken into consideration when aiming for repair of damaged myocardium by stem cell transplantation.
|Number of pages||9|
|Journal||International Journal of Cardiology|
|Publication status||Published - 1 Nov 2016|
Bibliographical noteFunding Information:
We thank Charlotte Nielsen, Tonja L. Jørgensen, and Anette Kliem (LMCC, Odense University Hospital) for their technical assistance. Funding: This work was supported by The Novo Nordisk Foundation, The Danish National Research Council (# 09-073648 ), The Lundbeck Foundation (# R48-A4785 and # R112-A9634 ), Lægeforeningen (# 2011-3271/480853-109 ), Tømrermester Alfred Andersen og Hustru's Fond , Hertha Christensens Foundation , Eva and Henry Frænkels Foundation , Odense University Hospital's Research Funding, and Department of Clinical Biochemistry and Pharmacology/ Odense University Hospital .
- Epicardial progenitors
- Heart infarct
- Myogenic specification
- Regenerating skeletal muscle
- Stem cell transplantation