Tissue Engineering and Regenerative Medicine

, Volume 9, Issue 6, pp 311–319

Direct comparison of distinct cardiomyogenic induction methodologies in human cardiac-derived c-kit positive progenitor cells

Original Article

DOI: 10.1007/s13770-012-0336-6

Cite this article as:
Choi, S.H., Jung, S.Y., Asahara, T. et al. Tissue Eng Regen Med (2012) 9: 311. doi:10.1007/s13770-012-0336-6

Abstract

Cardiac stem/progenitor cells can be differentiated into cardiomyocytes in vitro using several differentiation methodologies. However, the methodology of cardiomyogenic induction in human c-kit positive progenitor cells (hCPCsc-kit+) was not fully demonstrated. Thus, the purpose of our study was to directly evaluate each cardiomyocyte induction system using hCPCsc-kit+. In this study, cardiomyocyte induction methodologies were divided into the following three groups; treatment with dexamethasone, 5-azacytidine, and co-treatment with 5-azacytidine and Transforming Growth Factor Beta 1 (TGF-β1), using different serum concentrations [2% or 10% fetal bovine serum (FBS)]. GATA4 and Nkx2-5, cardiac-specific transcription factors, were expressed in our hCPCsckit+. However, the GATA4 and Nkx2-5 expressions were significantly decreased in 10% FBS/cardiomyogenic induction system (p < 0.01), whereas the GATA4 and Nkx2-5 expressions were preserved in 2% FBS/cardiomyogenic induction system (p > 0.05). GATA4 and Nkx2-5 is crucial roles in cardiac development, thus we considered the low serum conditions more affected in our cardiomyogenic induction system. In addition, c-kit expression decreased significantly during cardiomyogenic differentiation. Importantly, we demonstrated that co-treated with 5-azacytidine and TGF-β1 led to an earlier expression pattern of alpha-sarcomeric actin (α-SA), implying that this cardiomyocyte induction system facilitates early cardiomyocyte differentiation of hCPCsc-kit+. Thus, the present study provides a pivotal cardiomyogenic differentiation methodology using hCPCsc-kit+for basic or clinical research.

Key words

5-azacytidinecardiomyocyte differentiationdexamethasonehCPCsc-kit+TGF-β1

Copyright information

© The Korean Tissue Engineering and Regenerative Medicine Society and Springer Netherlands 2012

Authors and Affiliations

  1. 1.Laboratory of Cardiovascular Regeneration, Division of Cardiovascular Medicine, Seoul St. Mary’s HospitalThe Catholic University of Korea School of MedicineSeoulKorea
  2. 2.Laboratory of Vascular Medicine and Stem Cell Biology, Department of PhysiologyPusan National University School of MedicineYangsanKorea
  3. 3.Stem Cell Translational ResearchInstitute of Biomedical Research and Innovation/RIKKEN Center of Developmental BiologyKobeJapan
  4. 4.Department of Regenerative Medicine ScienceTokai University School of MedicineIseharaJapan
  5. 5.College of PharmacyAjou UniversitySuwonKorea