Abstract
Therapeutic delivery of cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs) represents a novel clinical approach to regenerate the injured myocardium. However, poor survival and contractility of these cells are a signifcant bottleneck to their clinical use. To better understand the role of cell-cell communication in enhancing the phenotype and contractile properties of hPSC-CMs, we developed a three-dimensional (3D) hydrogel composed of hPSC-CMs, human pluripotent stem cell-derived endothelial cells (hPSC-ECs), and/or human amniotic mesenchymal stem cells (hAMSCs). The objective of this study was to examine the role of multi-cellular interactions among hPSC-ECs and hAMSCs on the survival and long-term contractile phenotype of hPSC-CMs in a 3D hydrogel. Quantifcation of spontaneous contractility of hPSC-CMs in tri-culture demonstrated a 6-fold increase in the area of contractile motion after 6 weeks with characteristic rhythmic contraction frequency, when compared to hPSC-CMs alone (P < 0.05). This fnding was supported by a statistically signifcant increase in cardiac troponin T protein expression in the tri-culture hydrogel construct at 6 weeks, when compared to hPSC-CMs alone (P < 0.001). The sustained hPSC-CM survival and contractility in tri-culture was associated with a signifcant upregulation in the gene expression of L-type Ca2+ ion channel, Cav1.2, and the inward-rectifer potassium channel, Kir2.1 (P < 0.05), suggesting a role of ion channels in mediating these processes. These fndings demonstrate that multi-cellular interactions modulate hPSC-CM phenotype, function, and survival, and they will have important implications in engineering cardiac tissues for treatment of cardiovascular diseases.
Original language | English (US) |
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Pages (from-to) | 724-735 |
Number of pages | 12 |
Journal | American Journal of Translational Research |
Volume | 6 |
Issue number | 6 |
State | Published - 2014 |
Externally published | Yes |
Keywords
- Cardiac patch
- Cardiomyocyte
- Differentiation
- Endothelial cell
- Induced pluripotent stem cell
- Mesenchymal stem cell
ASJC Scopus subject areas
- Molecular Medicine
- Clinical Biochemistry
- Cancer Research