A fibrin-supported myocardial organ culture for isolation of cardiac stem cells via the recapitulation of cardiac homeostasis

Jong Tae Kim, Hye Jin Chung, Ji Yeon Seo, Young Il Yang, Min Young Choi, Hyeong In Kim, Tae Hyun Yang, Won Jin Lee, Young Chul Youn, Hye Jung Kim, Yeon Mee Kim, Hyukjin Lee, Yangsoo Jang, Seung Jin Lee

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)66-83
Number of pages18
JournalBiomaterials
Volume48
DOIs
Publication statusPublished - 2015 Apr 1

Fingerprint

Organ Culture Techniques
Stem cells
Fibrin
Cell culture
Homeostasis
Stem Cells
Stem Cell Niche
Cell signaling
Fibrinolysis
Microvessels
Cardiac Myocytes
Integrins
Cell Biology
Myocardium
Therapeutics
Growth

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Kim, Jong Tae ; Chung, Hye Jin ; Seo, Ji Yeon ; Yang, Young Il ; Choi, Min Young ; Kim, Hyeong In ; Yang, Tae Hyun ; Lee, Won Jin ; Youn, Young Chul ; Kim, Hye Jung ; Kim, Yeon Mee ; Lee, Hyukjin ; Jang, Yangsoo ; Lee, Seung Jin. / A fibrin-supported myocardial organ culture for isolation of cardiac stem cells via the recapitulation of cardiac homeostasis. In: Biomaterials. 2015 ; Vol. 48. pp. 66-83.
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Kim, JT, Chung, HJ, Seo, JY, Yang, YI, Choi, MY, Kim, HI, Yang, TH, Lee, WJ, Youn, YC, Kim, HJ, Kim, YM, Lee, H, Jang, Y & Lee, SJ 2015, 'A fibrin-supported myocardial organ culture for isolation of cardiac stem cells via the recapitulation of cardiac homeostasis', Biomaterials, vol. 48, pp. 66-83. https://doi.org/10.1016/j.biomaterials.2015.01.041

A fibrin-supported myocardial organ culture for isolation of cardiac stem cells via the recapitulation of cardiac homeostasis. / Kim, Jong Tae; Chung, Hye Jin; Seo, Ji Yeon; Yang, Young Il; Choi, Min Young; Kim, Hyeong In; Yang, Tae Hyun; Lee, Won Jin; Youn, Young Chul; Kim, Hye Jung; Kim, Yeon Mee; Lee, Hyukjin; Jang, Yangsoo; Lee, Seung Jin.

In: Biomaterials, Vol. 48, 01.04.2015, p. 66-83.

Research output: Contribution to journalArticle

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AU - Kim, Hyeong In

AU - Yang, Tae Hyun

AU - Lee, Won Jin

AU - Youn, Young Chul

AU - Kim, Hye Jung

AU - Kim, Yeon Mee

AU - Lee, Hyukjin

AU - Jang, Yangsoo

AU - Lee, Seung Jin

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N2 - 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.

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