There is great interest in the development of cardiac stem cells (CSCs) cell-based therapeutics; thus, clinical translation requires an efficient method for attaining therapeutic quantities of these cells. Furthermore, an invitro model to investigate the mechanisms regulating the cardiac homeostasis is crucial. We sought to develop a simple myocardial culture method for enabling both the recapitulation of myocardial homeostasis and the simultaneous isolation of CSCs. The intact myocardial fragments were encapsulated 3-dimensionally into the fibrin and cultured under dynamic conditions. The fibrin provided secure physical support and substratum to the myocardium, which mediated integrin-mediated cell signaling that allowed in situ renewal, outgrowth and cardiomyogenic differentiation of CSCs, mimicking myocardial homeostasis. Since our culture maintained the myocardial CSCs niches, it was possible to define the identity of invitro renewed CSCs that situated in the interstitium between cardiomyocytes and microvessels. Lastly, the use of matrix-restricted fibrinolysis enabled the selective isolation of outgrown CSCs that retained the clonogenicity, long-term growth competency and cardiovascular commitment potential. Collectively, this myocardial culture might be used as an alternative tool for studying cardiac biology and developing cell-based therapeutics.
|Number of pages||18|
|Publication status||Published - 2015 Apr 1|
Bibliographical noteFunding Information:
We greatly appreciate to thank members of Department of Cardiology, Busan Paik Hospital, for providing the Core Facility and for discussion and suggestions. We are indebted to B. Kim (Washington University in St. Louis) for assistance with animal surgery and maintenance. This work was supported by grants from National Research Foundation and Ministry of Education, Science and Technology of Korea ( NRF 2009-0060244 , NRF 2010-0027776 , NRF 2012-046885 , NRF 2014-A0403-00128 , MEST B020214 ) and by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare ( A120400 ). Any lab staff that made a large contribution to this project could go here.
All Science Journal Classification (ASJC) codes
- Ceramics and Composites
- Mechanics of Materials