Amniotic Fluid-Derived Stem Cells Demonstrated Cardiogenic Potential in Indirect Co-culture with Human Cardiac Cells
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Amniotic fluid-derived stem cells (AFSC) have been shown to be broadly multipotent and non-tumorogenic. Previous studies of direct mixing of AFSC and neonatal rat ventricle myocytes indicated evidence of AFSC cardiogenesis. In this study, we examined human AFSC cardiogenic potential in indirect co-culture with human cardiac cells in conditions that eliminated the possibility of cell fusion. Human AFSC in contact with human cardiac cells showed expression of cardiac troponin T (cTnT) in immunohistochemistry, and no evidence of cell fusion was found through fluorescent in situ hybridization. When indirectly co-cultured with cardiac cells, human AFSC in contact with cardiac cells across a thin porous membrane showed a statistically significant increase in cTnT expression compared to non-contact conditions but lacked upregulation of calcium modulating proteins and did not have functional or morphological characteristics of mature cardiomyocytes. This suggests that contact is a necessary but not sufficient condition for AFSC cardiac differentiation in co-culture with cardiac cells.
KeywordsCardiomyocytes Cardiac progenitor cells Right ventricular out flow tract Pediatric tissue engineering Congenital heart defects
Amniotic fluid derived stem cells
Congenital heart defects
Right ventricular out flow tract
Neonatal rat ventricular myocytes
This project is supported by the American Heart Association (Beginning Grant-in-Aid to JGJ.) Amniotic fluid samples were provided by the Fetal Center at Texas Children’s Hospital Pavilion for Women. Pediatric cardiac tissue samples were provided by Division of Congenital Heart Surgery at Texas Children’s Hospital through the Heart Center Biorepository.
There are no competing financial interests.
- 1.Acquistapace, A., T. Bru, P.-F. Lesault, F. Figeac, A. E. Coudert, O. le Coz, C. Christov, X. Baudin, F. Auber, R. Yiou, J.-L. Dubois-Randé, and A.-M. Rodriguez. Human mesenchymal stem cells reprogram adult cardiomyocytes toward a progenitor-like state through partial cell fusion and mitochondria transfer. Stem Cells (Dayton, Ohio) 29:812–824, 2011.Google Scholar
- 2.Benavides, O., and J. Petsche. Evaluation of endothelial cells differentiated from amniotic fluid-derived stem cells. Tissue Eng. Part A 18:1123–1131, 2012.Google Scholar
- 3.Bistola, V., M. Nikolopoulou, A. Derventzi, A. Kataki, N. Sfyras, N. Nikou, M. Toutouza, P. Toutouzas, C. Stefanadis, and M. M. Konstadoulakis. Long-term primary cultures of human adult atrial cardiac myocytes: cell viability, structural properties and BNP secretion in vitro. Int. J. Cardiol. 131:113–122, 2008.PubMedCrossRefGoogle Scholar
- 4.Chiavegato, A., S. Bollini, M. Pozzobon, A. Callegari, L. Gasparotto, J. Taiani, M. Piccoli, E. Lenzini, G. Gerosa, I. Vendramin, E. Cozzi, A. Angelini, L. Iop, G. F. Zanon, A. Atala, P. De Coppi, and S. Sartore. Human amniotic fluid-derived stem cells are rejected after transplantation in the myocardium of normal, ischemic, immuno-suppressed or immuno-deficient rat. J. Mol. Cell. Cardiol. 42:746–759, 2007.PubMedCrossRefGoogle Scholar
- 8.French, K. M., A. V. Boopathy, J. A. DeQuach, L. Chingozha, H. Lu, K. L. Christman, and M. E. Davis. A naturally derived cardiac extracellular matrix enhances cardiac progenitor cell behavior in vitro. Acta Biomater. 8:4357–4364, 2012.Google Scholar
- 9.Guan, X., and D. Delo. In vitro cardiomyogenic potential of human amniotic fluid stem cells. J. Tissue Eng. Regen. Med. 5:220–228, 2011. doi: 10.1002/term.
- 10.Hamilton, B. E., D. L. Hoyert, J. A. Martin, D. M. Strobino, and B. Guyer. Annual summary of vital statistics: 2010–2011. Pediatrics 131:548–558, 2013.Google Scholar
- 11.Harris, L., and S. Balaji. Arrhythmias in the adult with congenital heart disease. In: Diagnosis and Management of Adult Congenital Heart Disease, edited by M. Gatzoulis, G. Webb, and P. E. Daubeney. Philadelphia: Elsevier Health Sciences, 2003, pp. 105–113.Google Scholar
- 14.Kehat, I., and D. Kenyagin-Karsenti. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J. Clin. Invest. 108:363–364, 2001.Google Scholar
- 15.Mishra, R., K. Vijayan, E. J. Colletti, D. A. Harrington, T. S. Matthiesen, D. Simpson, S. K. Goh, B. L. Walker, G. Almeida-Porada, D. Wang, C. L. Backer, S. C. Dudley, L. E. Wold, and S. Kaushal. Characterization and functionality of cardiac progenitor cells in congenital heart patients. Circulation 123:364–73, 2011.Google Scholar
- 16.Moretti, A., L. Caron, A. Nakano, J. T. Lam, A. Bernshausen, Y. Chen, Y. Qyang, L. Bu, M. Sasaki, S. Martin-Puig, Y. Sun, S. M. Evans, K.-L. Laugwitz, and K. R. Chien. Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127:1151–1165, 2006.PubMedCrossRefGoogle Scholar
- 17.Murphy, S., J. Xu, and K. Kochanek. Deaths: final data for 2010. National Vital Statistics Reports 60, 2013.Google Scholar
- 18.Naqvi, N., M. Li, J. W. Calvert, T. Tejada, J. P. Lambert, J. Wu, S. H. Kesteven, S. R. Holman, T. Matsuda, J. D. Lovelock, W. W. Howard, S. E. Iismaa, A. Y. Chan, B. H. Crawford, M. B. Wagner, D. I. K. Martin, D. J. Lefer, R. M. Graham, and A. Husain. A proliferative burst during preadolescence establishes the final cardiomyocyte number. Cell 157:795–807, 2014.PubMedCrossRefGoogle Scholar
- 19.Nygren, J. M., S. Jovinge, M. Breitbach, P. Säwén, W. Röll, J. Hescheler, J. Taneera, B. K. Fleischmann, and S. E. W. Jacobsen. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat. Med. 10:494–501, 2004.PubMedCrossRefGoogle Scholar
- 20.Oh, H., S. B. Bradfute, T. D. Gallardo, T. Nakamura, V. Gaussin, Y. Mishina, J. Pocius, L. H. Michael, R. R. Behringer, D. J. Garry, M. L. Entman, and M. D. Schneider. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc. Natl Acad. Sci. U.S.A. 100:12313–12318, 2003.PubMedCentralPubMedCrossRefGoogle Scholar
- 23.Reller, M., and M. Strickland. Prevalence of congenital heart defects in metropolitan Atlanta, 1998–2005. J. Pediatrics 153:807–813, 2008.Google Scholar
- 24.Schuldiner, M., O. Yanuka, J. Itskovitz-Eldor, D. A. Melton, and N. Benvenisty. Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc. Natl Acad. Sci. U.S.A. 97:11307–12, 2000.Google Scholar
- 27.Wozniak, M. A., and C. S. Chen. Mechanotransduction in development: a growing role for contractility. Nature reviews. Mol. Cell Biol. 10:34–43, 2009.Google Scholar
- 28.Xin, M., Y. Kim, L. B. Sutherland, M. Murakami, X. Qi, J. McAnally, E. R. Porrello, A. I. Mahmoud, W. Tan, J. M. Shelton, J. A. Richardson, H. A. Sadek, R. Bassel-Duby, and E. N. Olson. Hippo pathway effector Yap promotes cardiac regeneration. Proc. Natl Acad. Sci. U.S.A. 110:13839–13844, 2013.Google Scholar
- 31.Zimmermann, W.-H., I. Melnychenko, G. Wasmeier, M. Didié, H. Naito, U. Nixdorff, A. Hess, L. Budinsky, K. Brune, B. Michaelis, S. Dhein, A. Schwoerer, H. Ehmke, and T. Eschenhagen. Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat. Med. 12:452–458, 2006.PubMedCrossRefGoogle Scholar