Research article Topical Sections

Cardiomyotic induction and proliferation of dental stem cells on electrospun scaffolds

  • Received: 22 February 2016 Accepted: 30 March 2016 Published: 04 April 2016
  • Stem cells from human exfoliated deciduous teeth (SHED) are a unique source of stem cells because they are relatively easy to obtain and harvest from discarded teeth. While they could differentiate into neurons, adipocytes, osteoblasts, and myocytes, little is known whether they can differentiate into cardiomyocytes. The potential use of a biomaterial scaffold to deliver cardiomyocytes to the site of damaged heart tissue for cellular therapy is an attractive concept. Gelatin-B and poly-(lactic-co-glycolic acid) (PLGA) were selected for the present study. The gelatin-B and PLGA scaffolds were constructed using an electro-spinning technique. SHED cells proliferate in both PLGA scaffolds and gelatin-B scaffolds and maintain adequate viability as determined with calcein-AM staining and DNA quantification. SHED cells were treated with a predetermined optimized cardio-treatment protocol. qPCR analysis of the cardiomyotic genes, MEF2.C, Cx-43, TNNT2.C, Nkx2.5, and GATA-4, showed that SHED cells differentiated on PLGA significantly up-regulated these cardiogenic markers compared to SHED cells cultured in control media . In summary, we demonstrate the growth and cardiomyogenesis of SHED cells on electrospun gelatin and PLGA scaffolds. Further development of our research concepts for cardiovascular regeneration using in vivo research and clinical trials, could allow the development of therapies involving the delivery of cardiomyocytes differentiated from SHED using electrospun scaffolds to the site of damaged heart tissue.

    Citation: Pornchai Kittivarakarn, Matthew Penna, Zenith Acosta, Daniel Pelaez, Ramon Montero, Fotios M. Andreopoulos, Herman S. Cheung. Cardiomyotic induction and proliferation of dental stem cells on electrospun scaffolds[J]. AIMS Bioengineering, 2016, 3(2): 139-155. doi: 10.3934/bioeng.2016.2.139

    Related Papers:

  • Stem cells from human exfoliated deciduous teeth (SHED) are a unique source of stem cells because they are relatively easy to obtain and harvest from discarded teeth. While they could differentiate into neurons, adipocytes, osteoblasts, and myocytes, little is known whether they can differentiate into cardiomyocytes. The potential use of a biomaterial scaffold to deliver cardiomyocytes to the site of damaged heart tissue for cellular therapy is an attractive concept. Gelatin-B and poly-(lactic-co-glycolic acid) (PLGA) were selected for the present study. The gelatin-B and PLGA scaffolds were constructed using an electro-spinning technique. SHED cells proliferate in both PLGA scaffolds and gelatin-B scaffolds and maintain adequate viability as determined with calcein-AM staining and DNA quantification. SHED cells were treated with a predetermined optimized cardio-treatment protocol. qPCR analysis of the cardiomyotic genes, MEF2.C, Cx-43, TNNT2.C, Nkx2.5, and GATA-4, showed that SHED cells differentiated on PLGA significantly up-regulated these cardiogenic markers compared to SHED cells cultured in control media . In summary, we demonstrate the growth and cardiomyogenesis of SHED cells on electrospun gelatin and PLGA scaffolds. Further development of our research concepts for cardiovascular regeneration using in vivo research and clinical trials, could allow the development of therapies involving the delivery of cardiomyocytes differentiated from SHED using electrospun scaffolds to the site of damaged heart tissue.


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    [1] Heron M, Hoyert D, Murphy S, et al. (2009) Deaths: Final data for 2006. National Vital Statistics Reports 57: 14.
    [2] Segers V, Lee R (2008) Stem-cell therapy for cardiac disease. Nature 45: 937–942.
    [3] Wu X, Ding S, Ding Q, et al. (2004) Small molecules that induce cardiomyogenesis in embryonic stem cells. J Am Chem Soc 126: 1590–1591. doi: 10.1021/ja038950i
    [4] Buggisch M, Ateghang B, Ruhe C, et al. (2007) Stimulation of ES-cell-derived cardiomyogenesis and neonatal cardiac cell proliferation by reactive oxygen species and NADPH oxidase. J Cell Sci: 885–894.
    [5] Jankowski M, Danalache B, Wang D, et al. (2004) Oxytocin in cardiac ontogeny. P Natl Acad Sci U S A 35: 13074–13079.
    [6] Paquin J, Danalache B, Jankowski M, et al. (2002) Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes. P Natl Acad Sci U S A 99: 9550–9555.
    [7] Antonitsis P, Ioannidou-Papagiannaki E, Kaidoglou A, et al. (2008) Cardiomyogenic potential of human adult bone marrow mesenchymal stem cells in vitro. J Thorac Cardiovasc Surg 56: 77–82.
    [8] Labovsky V, Hofer E, Feldman L, et al. (2010) Cardiomyogenic differentiation of human bone marrow mesenchymal cells: role of cardiac extract from neonatal rat cardiomyocytes. Differentiation 79: 93–101.
    [9] Doble B, Kardami E (1995) Basic fibroblast growth factor stimulates connexin-43 expression and intercellular communication of cardiac fibroblasts. Mol Cell Biochem 143: 81–87.
    [10] Long C (1996) Autocrine and paracrine regulation of myocardial cell growth in vitro: the TGF beta paradigm. Trends Cardiovasc Med 6: 217–226.
    [11] Ito H, Hiroe M, Tsujino M, et al. (1993) Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes. Circulation: Am Heart J 87: 1715–1721.
    [12] Hefti M, Harder B, Eppendberger H, et al. (1997) Signaling pathways in cardiac myocyte hypertrophy. J Mol Cell Cardiol 29: 2873–2892.
    [13] Ling-Ling E, Zhao Y, Guo X, et al. (2005) Enrichment of cardiomyocytes derived from mouse embryonic stem cells. J Heart Lung Transplant 25: 664–674.
    [14] Schultheiss T, Burch J, Lassar A (1997) A role for bone morphogenetic proteins in the induction of cardiac myogenesis. Genes Dev 11: 451–462.
    [15] Hiep N, Lee B (2010). Electro-spinning of PLGA/PCL blends for tissue engineering and their biocompatibility. J Mater Sci Mater Med 21: 1969–1978.
    [16] Ifkovitz J, Sundararaghavan H, Burdick J (2009) Electrospinning fibrous polymer scaffolds for tissue engineering and cell culture. J Vis Exp 32.
    [17] Miura M, Gronthos S, Zhao M, et al. (2003) SHED: Stem cells from human exfoliated deciduous teeth. P Natl Acad Sci U S A 100: 5807–5812.
    [18] Huang G, Gronthos S, Shi S (2009) Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 88: 792–806.
    [19] Kerkis I, Kerkis A, Dozortsez D, et al. (2006) Isolation and characterization of a population of immature dental pulp stem cells expressing oct-4 and other embyronic stem cell markers. Cells Tissues Organs: 105–116.
    [20] Pfaffl M (2001). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29: 45.
    [21] QIAGEN (2011). Gentra® Puregene® Handbook, 3rd Eds.
    [22] Hamamoto H, Gorman J, Ryan L, et al. (2009). Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial. Ann Thorac Surg. 87: 794–801.
    [23] Brignier A, Gewirtz A (2010) Embryonic and adult stem cell therapy. J Allergy Clin Immunol: 336–344.
    [24] Hofmann M, Wollert K, Meyer G, et al. (2005) Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 111: 2198–2202. doi: 10.1161/01.CIR.0000163546.27639.AA
    [25] Velez C, Aranega E, Melguizo C, et al. (1994) Modulation of contractile protein troponin-T in chick myocardial cells by basic fibroblast growth factor and platelet-derived growth factor during development. J Cardiovasc Pharmacol 24: 906–913. doi: 10.1097/00005344-199424060-00007
    [26] Lourenco D, Brauner R, Rybczynska M, et al. (2011). Loss-of-function mutation in GATA4 causes anomalies of human testicular development. P Natl Acad Sci U S A 108: 1597–1602.
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