Induced Pluripotent Stem Cells
Applied to the Field of Regenerative Medicine
Imagine having the opportunity to travel back in time with the power to alter the outcome of the future. As pleasing as this may sound, such occurrences just do not seem realistic or even possible in today’s world. Although, if we take a step back and look into time travel on a smaller scale, at the cellular level, it is indeed possible to revert to an earlier stage of life. Specifically focusing on terminally differentiated somatic cells, scientists are now able to induce pluripotency thanks to the findings from Sir John B. Gurdon, and Shinya Yamanaka. Findings from Gurdon’s paper inform us that all cells in an organism contain the same genetic information. The difference in gene expression leads to one cell type over another. This implies that somatic cells should have the ability to give rise to a variety of cell types under the appropriate conditions because all of the cells have the same DNA content. Findings from Yamanaka’s paper tell us that the factors responsible from the maintenance of pluripotency in early embryos and embryonic stem cells also are responsible for inducing pluripotency in somatic cells. The factors from Yamanaka’s discovery are OCT-3/4, KLF4, SOX2, and c-MYC; these four transcription factors work together to effectively induce pluripotency and have greatly advanced the technological applications of genetic reprogramming. The field of regenerative medicine has especially benefitted from the genetic reprogramming advances. One of the main goals of regenerative medicine is to restore structures of damaged tissues as well as to restore functions of damaged organs1 . A major application for regenerative medicine is in the field of cardiovascular medicine. The use of regenerative medicine for cardiovascular disease treatment is appealing because it is much less invasive that transplantation and open-heart surgery. In order to determine which combination transcription factors are able to create normal cell fates from the damaged cardiac tissue, induced pluripotent stem cells are an intricate part of the drug screening technique often used. The drugs capable of inducing pluripotency and repairing the damaged tissue have the potential to treat cardiovascular disease in human patients. Alternative options for repairing damaged tissue include transplantation of new organs from donors. Cardiovascular diseases continue to account for the leading cause of death in America2. Due to the high frequency of deaths caused by heart malfunctions in society, researchers are constantly trying to discover new ways for treatment and prevention. Despite the alternative methods used to treat cardiovascular diseases, the use of induced pluripotent stem cells for regenerative medicine is overall beneficial to the field of cardiovascular medicine because it is a less invasive option that can effectively restore wounded cardiac tissue by replacing cardiomyocytes and reducing occurrences of fibrosis (Poon, 2011). Using induced pluripotent stem cells is a much less invasive means for cardiovascular repair than other options, such as transplanting an entire heart. Before regenerative medicine had the clinical potential it currently possesses, scientists first needed to have a comprehensive understanding of the heart and its development processes. Muscle tissue in the heart is referred to as cardiac muscle. One cell type that encompasses cardiac muscle is the cardiomyocyte. Each mature adult cardiomyocyte only contains a single, unique nucleus and expresses cardiac transcriptions factors, which allows for their calcium ion handling and contractile properties (Poon, 2011). Normally, these adult cardiomyocytes cannot regenerate once damaged (Poon). This leads to the malfunction or loss of function within the heart, causing many of the heart conditions prevalent in society. Studies show that induced pluripotent stem cells can differentiate into the...
References: Poon E, Kong CW, Li RA. Human pluripotent stem cell-based approaches for myocardial repair: from the electrophysiological perspective. Mol Pharm. 2011 Oct 3; 8(5):1495-504. doi: 10.1021/mp2002363. Epub 2011 Sep 8.
Song K, Nam YJ, Luo X, Qi X, Tan W, Huang GN, Acharya A, Smith CL, Tallquist MD, Neilson EG, Hill JA, Bassel-Duby R, Olson EN. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature. 2012 May 13; 485(7400):599-604. doi: 10.1038/nature11139.
Mehta A, Chung YY, Ng A, Iskandar F, Atan S, Wei H, Dusting G, Sun W, Wong P, Shim W. Pharmacological response of human cardiomyocytes derived from virus-free induced pluripotent stem cells. Cardiovasc Res. 2011 Sep 1;91(4):577-86. doi: 10.1093/cvr/cvr132. Epub 2011 May 12.
Kawamura M, Miyagawa S, Miki K, Saito A, Fukushima S, Higuchi T, Kawamura T, Kuratani T, Daimon T, Shimizu T, Okano T, Sawa Y. Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation. 2008 Jul 29;118(5):507-17. doi:10.1161/CIRCULATIONAHA.108.778795. Epub 2008 Jul 14.
Richardson, P. et al.; McKenna, W; Bristow, M; Maisch, B; Mautner, B; O 'Connell, J; Olsen, E; Thiene, G et al. (1996). "Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies". Circulation 93 (5): 841–2. doi:10.1161/01.CIR.93.5.841.PMID 8598070
Please join StudyMode to read the full document