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

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.

Resistance to Cisplatin Renders High Metastatic Potential in Human Non-Small Cell Lung Cancer Cell Line / 대한흉부외과학회지

BACKGROUND: Resistance to cytotoxic drugs such as cisplatin is an important cause of treatment failure in lung cancer. The mechanisms are omplex and have yet to be clearly elucidated, but the acquisition of drug resistance possibly has resulted in poor survival. The purpose of the study is to evaluate whether the resistant tumor cells would gain more potential for metastasis. MATERIAL AND METHOD: we examined the metastatic potential of a cisplatin-reisistant cell line, H460/CIS, which was established from the human lung cancer cell line H460 by in vitro selection with gradually increased concentration of cisplatin. The parental cisplatin-sensitive cell line(H460) was used as the control and analysis on the expression of angiogenesis or growth-related factors, gelatin zymographic analysis and in vivo spontaneous metastatic experiment in nude mice were done. RESULT: Increased levels of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor (bFGF) were found in H460/CIS. Gelatin zymographic analyses showed that proteinase A in the culture medium of H460/CIS was processed from latent to activated form. The in vivo experiment showed that H460/CIS cells spontaneously metastasized to the lungs but parental cells did not. CONCLUSION: resistance to the chemotherapeutic agents may render the tumor aggressi-veness and metastatic potential. Therefore, the risk, rather than benefit, from inadvertent application of adj uvant or neoadj uvant chemotherapy to early-staged lung cancer should be considered.