Cor Vasa 2022, 64(6):589-594 | DOI: 10.33678/cor.2022.033

Association between reversine dose and increased plasticity of dedifferentiated fat (DFAT cells) into cardiac derived cells

Muhammad Firdani Ramadhan, Yudi Her Oktaviono, Budi Baktijasa Dharmadjati, Ryan Enast Intan
Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Airlangga - Dr. Soetomo General Hospital, Surabaya, East Java, Indonesia

Aim: To analyze the association between reversine and increased plasticity of DFAT into cardiac derivative cells.

Method: The cultured DFAT cells were divided into four groups based on reversine dose: control (no reversine), 10 nM, 20 nM, and 40 nM reversine. Each group will go through several stages of passage before further differentiation into cardiomyocytes (marked by cTnT expression), VSCMs (marked by alpha-SMA expression), and vascular endothelial cells (marked by alpha-SMA expression) (marked by CD31 expression).

Result: There were significant differences in the expression of cTnT, alpha-SMA, and CD31 (p = 0.003, p <0.001, and p <0.001, respectively) in each group of DFAT cells that received reversine. From post-hoc analysis with Tukey test, it was found that only the 10 nM reversine group produced a significant difference compared to the control group (p = 0.002) for cTnT expression and reversine 10 nM and 20 nM group for α-SMA expression and CD31 expression (p = 0.028 and p <0.001, respectively).

Conclusions: This study proves that there is a relationship between reversine and increased plasticity of DFAT cells into cardiac derived cells in the form of cardiomyocytes (cTnT), VSMCs (alpha-SMA), and vascular endothelial cells (CD31).

Keywords: Cardiomyocyte, DFAT, Reversine, Vascular endothelial cells, VSMCs

Received: March 6, 2022; Revised: March 6, 2022; Accepted: April 3, 2022; Published: December 15, 2022  Show citation

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Ramadhan MF, Her Oktaviono Y, Dharmadjati BB, Intan RE. Association between reversine dose and increased plasticity of dedifferentiated fat (DFAT cells) into cardiac derived cells. Cor Vasa. 2022;64(6):589-594. doi: 10.33678/cor.2022.033.
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References

  1. Vasan RS, Benjamin EJ. The future of cardiovascular epidemiology. Circulation 2016;133:2626-2633. Go to original source... Go to PubMed...
  2. World Health Organization, NCDs Country Profiles 2018 WHO (2018) 224.
  3. Hussain MA, Al Mamun A, Peters SA, et al. The Burden of Cardiovascular Disease Attributable to Major Modifiable Risk Factors in Indonesia. J Epidemiol 2016;26:515-521. Go to original source... Go to PubMed...
  4. Xu Q. The impact of progenitor cells in atherosclerosis. Nat Clin Pract Cardiovasc Med 2006;3:94-101. Go to original source... Go to PubMed...
  5. Menasche P. Cell-based therapy for heart disease: A clinically oriented perspective. Mol Ther 2009;17:758-766. Go to original source... Go to PubMed...
  6. Chagastelles PC, Nardi NB., Biology of stem cells: An overview. Kidney Int. Suppl 2011;1:63-67. Go to original source... Go to PubMed...
  7. Wollert KC, Drexler H. Cell therapy for the treatment of coronary heart disease: a critical appraisal. Nat Rev Cardiol 2010;7:204-215. Go to original source... Go to PubMed...
  8. Doeppner TR, Hermann DM. Stem cell-based treatments against stroke: Observations from human proof-of-concept studies and considerations regarding clinical applicability. Front Cell Neurosci 2014;8:357. Go to original source... Go to PubMed...
  9. Poloni A, Maurizi G, Leoni P, et al. Human dedifferentiated adipocytes show similar properties to bone marrow-derived mesenchymal stem cells. Stem Cells 2012;30:965-974. Go to original source... Go to PubMed...
  10. Lessard J, Pelletier M, Biertho L, et al. Characterization of dedifferentiating human mature adipocytes from the visceral and subcutaneous fat compartments: fibroblast-activation protein alpha and dipeptidyl peptidase 4 as major components of matrix remodeling. PLoS One 2015;10:e0122065. Go to original source... Go to PubMed...
  11. Wei S, Duarte MS, Zan L, et al. Cellular and Molecular Implications of Mature Adipocyte Dedifferentiation. J Genomics 2013;1:5-12. Go to original source... Go to PubMed...
  12. Wanjare M, Kuo F, Gerecht S. Derivation and maturation of synthetic and contractile vascular smooth muscle cells from human pluripotent stem cells. Cardiovasc Res 2013;97:321-330. Go to original source... Go to PubMed...
  13. Watanabe H, Goto S, Kato R, et al. The neovascularization effect of dedifferentiated fat cells. Sci Rep 2020;10:9211. Go to original source... Go to PubMed...
  14. Ayoubi S, Sheikh SP, Eskildsen TV. Human induced pluripotent stemcell-derived vascular smooth muscle cells: Differentiation and therapeutic potential. Cardiovasc Res 2017;113:1282-1293. Go to original source... Go to PubMed...
  15. Lu YC, Lee YR, Der Liao J, et al. Reversine induced multinucleated cells, cell apoptosis and autophagy in human non-small cell lung cancer cells. PLoS One 2016;11:e0158587. Go to original source... Go to PubMed...
  16. Huang Y, Huang D, Weng J, et al. Effect of reversine on cell cycle, apoptosis, and activation of hepatic stellate cells. Mol Cell Biochem 2016;423:9-20. Go to original source... Go to PubMed...
  17. Higgins JE, Kleinbaum AP. Design trials, methodology for randomized clinical trials. USA: Family Health International.
  18. Jumabay M. Dedifferentiated fat cells: A cell source for regenerative medicine. World J Stem Cells 2015;7:1202-1214. Go to original source... Go to PubMed...
  19. Saler M, Caliogna L, Botta L, et al. hASC and DFAT, multipotent stem cells for regenerative medicine: A comparison of their potential differentiation in vitro. Int J Mol Sci 2017;18:2699. Go to original source... Go to PubMed...
  20. Shah M, George RL, Evancho-Chapman MM, Zhang G. Current challenges in dedifferentiated fat cells research. Organogenesis 2016;12:119-127. Go to original source... Go to PubMed...
  21. Jumabay M, Matsumoto T, Yokoyama S, et al. Dedifferentiated fat cells convert to cardiomyocyte phenotype and repair infarcted cardiac tissue in rats. J Mol Cell Cardiol 2009;47:565-575. Go to original source... Go to PubMed...
  22. Chen S, Zhang Q, Wu X, et al. Dedifferentiation of lineage-committed cells by a small molecule. J Am Chem Soc 2004;126:410-411. Go to original source... Go to PubMed...
  23. Soltani L, Rahmani HR, Daliri Joupari M, et al. Effects of Different Concentrations of Reversine on Plasticity of Mesenchymal Stem Cells. Indian J Clin Biochem 2020;35:188-196. Go to original source... Go to PubMed...
  24. Hiruma Y, Koch A, Dharadhar S, et al. Structural basis of reversine selectivity in inhibiting Mps1 more potently than aurora B kinase. Proteins 2016;84:1761-1766. Go to original source... Go to PubMed...
  25. Sabbattini P, Canzonetta C, Sjoberg M, et al. A novel role for the Aurora B kinase in epigenetic marking of silent chromatin in differentiated postmitotic cells. EMBO J 2007;26:4657-4669. Go to original source... Go to PubMed...
  26. Li C, Li M, Li S, et al. Progenitors of secondary crest myofibroblasts are developmentally committed in early lung mesoderm. Stem Cells 2015;33:999-1012. Go to original source... Go to PubMed...
  27. Anastasia L, Sampaolesi M, Papini N, et al. Reversine-treated fibroblasts acquire myogenic competence in vitro and in regenerating skeletal muscle. Cell Death Differ 2006;13:2042-2051. Go to original source... Go to PubMed...
  28. Kolch W. Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat Rev Mol Cell Biol 2005;6:827-837. Go to original source... Go to PubMed...
  29. Guo Y, Zhu H, Li X, et al. Multiple functions of reversine on the biological characteristics of sheep fibroblasts. Sci Rep 2021;11:12365. Go to original source... Go to PubMed...
  30. Park YL, Ha SY, Park SY, et al. Reversine induces cell cycle arrest and apoptosis via upregulation of the Fas and DR5 signaling pathways in human colorectal cancer cells. Int J Oncol 2019;54:1875-1883. Go to original source... Go to PubMed...

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