title: A fibrin-supported myocardial organ culture for isolation of cardiac stem cells via the recapitulation of cardiac homeostasis.
abstract: 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 in vitro 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 in vitro 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.
authors.affiliation: Paik Institute for Clinical Research, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Jong-Tae
authors.initials: JT
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Chung
authors.affiliation: Paik Institute for Clinical Research, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Seo
authors.affiliation: Paik Institute for Clinical Research, Inje University College of Medicine, Busan 614-735, Republic of Korea. Electronic address: pathyang@inje.ac.kr.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Yang
authors.affiliation: Paik Institute for Clinical Research, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Choi
authors.affiliation: Paik Institute for Clinical Research, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Hyeong-In
authors.initials: HI
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Yang
authors.affiliation: Paik Institute for Clinical Research, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Won-Jin
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Paik Institute for Clinical Research, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Youn
authors.affiliation: Paik Institute for Clinical Research, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Paik Institute for Clinical Research, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Yeon Mee
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Hyukjin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Yang-Soo
authors.initials: YS
authors.lastname: Jang
authors.affiliation: Department of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea. Electronic address: sjlee@ewha.ac.kr.
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002455:Cell Division; D005337:Fibrin; D006706:Homeostasis; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000276:immunology; D009924:Organ Culture Techniques; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology
chemical_list: D005337:Fibrin
keywords: Cardiac homeostasis; Cardiac stem cells; Fibrin; Myocardial infarction; Organ culture; Stem cell niche