Korean J Thorac Cardiovasc Surg.  2006 Jul;39(7):511-519.

Transformation of Adult Mesenchymal Stem Cells into Cardiomyocytes with 5-azacytidine: Isolated from the Adipose Tissues of Rat

• Choe JW
• Kim YI
• Oh TY
• Cho DY
• Sohn DS
• Lee TJ

Abstract

BACKGROUND: Loss of cardiomyocytes in the myocardial infarction leads to regional contractile dysfunction, and necrotized cardiomyocytes in infracted ventricular tissues are progressively replaced by fibroblasts forming scar tissue. Although cardiomyoplasty, or implantation of ventricular assist device or artificial heart was tried in refractory heart failure, the cardiac transplantation was the only therapeutic modality because these other therapeutic strategies were not permanent. Cell transplantation is tried instead of cardiac transplantation, especially bone marrow is the most popular donated organ. But because bone marrow aspiration procedure is invasive and painful, and it had the fewer amounts of cellular population, the adipose tissue is recommended for harvesting of mesenchymal stem cells. MATERIAL AND METHOD: After adipose tissues were extracted from abdominal subcutaneous adipose tissue and intra-abdominal adipose tissue individually, the cellular components were obtained by same method. These cellular components were tried to transformation with the various titers of 5-azacytidine to descript the appropriate concentration of 5-azacytidine and possibility of transformation ability of adipose tissue. Group 1 is abdominal subcutaneous adipose tissue and Group 2 is intra-abdominal adipose tissue-retroperitoneal adipose tissue and omentum. Cellular components were extracted by collagenase and NH4Cl et al, and these components were cultured by non-induction media-DMEM media containing 10% FBS and inducted by none, 3 micromol/L, 6 micromol/L, and 9 micromol/L 5-azacytidine after the 1st and 2nd subculture. After 4 weeks incubation, the cell blocks were made, immunostaining was done with the antibodies of CD34, heavy myosin chain, troponin T, and SMA. RESULT: Immunostaining of the transformed cells for troponin T was positive in the 6 micromol/L & 9 micromol/L 5-azacytidine of Group 1 & 2, but CD34 and heavy myosin chain antibodies were negative and SMA antibody was positive in the 3 micromol/L & 6 micromol/L 5-azacytidne of Group 2.
CONCLUSION
These observations confirm that adult mesenchymal stem cells isolated from the abdominal subcutaneous adipose tissues and intra-abdominal adipose tissues can be chemically transformed into cardiomyocytes. This can potentially be a source of autologous cells for myocardial repair.

Keyword

Cell biology; Cell tansplantation; Myocardium-cytology; Rats

MeSH Terms

Adipose Tissue
Adult*
Animals
Antibodies
Azacitidine*
Bone Marrow
Cardiomyoplasty
Cell Transplantation
Cicatrix
Collagenases
Fibroblasts
Heart Failure
Heart Transplantation
Heart, Artificial
Heart-Assist Devices
Humans
Intra-Abdominal Fat
Mesenchymal Stromal Cells*
Myocardial Infarction
Myocytes, Cardiac*
Myosins
Omentum
Rats*
Subcutaneous Fat, Abdominal
Transplants
Troponin T
Antibodies
Azacitidine
Collagenases
Myosins
Troponin T