Abstract 12965: Higher Cardiac Differentiation Properties are Evident in Long Term Cultured Induced Pluripotent Stem Cells Obtained From Atrial Mesenchymal Cells Compared to Skin Mesenchymal Cells
Introduction: Mesenchymal stromal cells from adult atrial tissue (A-MSC) retain the ability to differentiate into cardiovascular cell types better than syngeneic cells of non-cardiac origin both in vitro and in vivo. Of note, A-MSC exhibit a tissue-specific miR signature unaffected by in vitro differentiation media. Prior studies have demonstrated that founder cell types could influence the molecular and developmental properties of induced pluripotent stem cells (iPSC) via epigenetic memory. As crucial modulators of cell fate and differentiation, microRNA (miR) have been hypothesized to act as major players in this process.
Hypothesis: Aims of the work were to evaluate the maintenance of functional memory of the founder organ in iPSC generated from syngeneic stromal cells (fibroblasts) of cardiac and skin origin and whether A-iPSC cardiac memory is associated with specific miR modulation.
Results: We found that long term cultured (passage >13) A-iPSC produced a higher number of beating embryoid bodies than iPSC from skin MSC (S-iPSC). Notably, cardiomyocytes derived from A-iPSC displayed higher expression of sarcomeric proteins (MYLC2.a, α-Sarc, α-MHC, β-MHC), ion channels (HCN1, HCN2, HCN4, CACNA1C, CACNA1G) and cardiac-specific miR (miR-1, -133a, -133b). Moreover, A-iPSC-derived cardiomyocytes showed a higher degree of electrical maturation, such as more hyperpolarized diastolic potential and larger action potential amplitude than S-iPSC. Importantly, different groups of miRNA were differentially modulated in A- vs S- MSC during the reprogramming process. Gene-enrichment analysis revealed that miR associated to the reprogramming of A-MSC specifically target VEGF and TGF-β pathways, which are crucial for cardiac differentiation and also histone deacetylase (HDAC) binding genes, known to promote myocardial repair, prevents cardiac remodeling and induces the entry of mesodermal cells into the cardiac muscle.
Conclusions: Our results support the notion that iPSC retain a memory of their origin tissue and, as a consequence, have better cardiac differentiation capability. The evidence that miR are differentially regulated during the reprogramming supports the idea that they can play a role in establishing this difference.
Author Disclosures: V. Meraviglia: None. J. Wen: None. L. Piacentini: None. G. Campostrini: None. C. Wang: None. V. Azzimato: None. J. Wong: None. C. Gaetano: None. G. Pompilio: None. A. Barbuti: None. D. DiFrancesco: None. P.P. Pramstaller: None. G.I. Colombo: None. V.H. Chen: None. A. Rossini: None.
- © 2014 by American Heart Association, Inc.