Original Article

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

  • Sung Hyun ChoiAffiliated withLaboratory of Cardiovascular Regeneration, Division of Cardiovascular Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea School of Medicine
  • , Seok Yun JungAffiliated withLaboratory of Vascular Medicine and Stem Cell Biology, Department of Physiology, Pusan National University School of Medicine
  • , Takayuki AsaharaAffiliated withStem Cell Translational Research, Institute of Biomedical Research and Innovation/RIKKEN Center of Developmental BiologyDepartment of Regenerative Medicine Science, Tokai University School of Medicine
  • , Wonhee SuhAffiliated withCollege of Pharmacy, Ajou University
  • , Sang-Mo KwonAffiliated withLaboratory of Cardiovascular Regeneration, Division of Cardiovascular Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea School of Medicine Email author 
  • , Sang Hong BaekAffiliated withLaboratory of Cardiovascular Regeneration, Division of Cardiovascular Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea School of Medicine Email author 

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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 hCPCs c-kit+ for basic or clinical research.

Key words

5-azacytidine cardiomyocyte differentiation dexamethasone hCPCsc-kit+ TGF-β1