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Epigenetic reprogramming by valproic acid (VPA) induces intermediate pluripotency in human amniotic mesenchymal stem cells (hAMSCs). The hAMSCs dedifferentiate into precardiac mesoderms to undergo direct transdifferentiation into cardiac progenitor-like cells, using Wnt-pathway specific small molecules.
The hAMSCs were isolated from the human placenta amniotic membrane. The cells were transferred to human embryonic stem cell (hESC) culture condition. Flow cytometry was performed after VPA treatment. The hAMSCs were divided into 3 treatment groups: 1) LIF, CHIR, BMP4 and IWR, 2) LIF, CHIR, ActivinA, BMP4 and IWR and 3) CHIR and IWR. Real time PCR was performed.
The hAMSCs underwent robust non-integrative epigenetic reprogramming using VPA in hESC culture condition to generate a dedifferentiated, partially reprogrammed population of hAMSCs yielding approximately, 50% TRA-1-60+ population. Relative quantification (RQ) using real time PCR demonstrated 250-500 fold increase in brachyury, GATA4, and Nkx2.5 expression. Sequential administration of LIF, BMP, CHIR, and IWR increased the expression of similar genes and mesp1to 3,000-5,000-fold, consistent with a developmental profile of cardiac progenitor cells (Figure).
VPA and sequential administration of Wnt-specific small molecules generated cardiac progenitor-like cells. Further studies to assess their in vivo cardiac regenerative effects are underway.
Poster Sessions, Expo North
Saturday, March 09, 2013, 3:45 p.m.-4:30 p.m.
Session Title: Novel Therapeutic Targets in Hearts Failure
Abstract Category: 16. Heart Failure: Basic
Presentation Number: 1176-292
- 2013 American College of Cardiology Foundation