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Developmental Factors Create a Niche for Cardiac Regeneration
Author(s) -
Perrera Alec Bennett,
Hoffman Kristen D,
Camenisch Todd D
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1119.21
Subject(s) - microbiology and biotechnology , reprogramming , regeneration (biology) , regenerative medicine , mesenchymal stem cell , myocardial infarction , mef2c , cellular differentiation , heart development , stem cell , biology , embryonic stem cell , medicine , cell , transcription factor , biochemistry , genetics , gene
Heart disease is the number one cause of death in the United States. The adult mammalian heart has limited ability to repair itself, which is not sufficient to regenerate myocardial tissue injured by myocardial infarction (MI). Previous research has established that cardiac fibroblasts can be reprogrammed to adult cardiomyocyte‐like cells in vitro by administration of Gata4, Mef2c, and Tbx5 (GMT) as well as thymosin β4 (Tβ4). We have reported previously that hyaluronan (HA) supports a hematopoietic niche in the bone marrow as well as serving as a vital biomolecule for endocardial cushion and epicardial development during mouse embryogenesis. Epicardial cells are also implicated in myocardial regeneration, however the mechanisms of how this occurs in mammalian cells is not clear. TGFβ2 and HA are important for the induction of epicardial cell differentiation and invasion through regulation of epithelial to mesenchymal transformation (EMT). Thus, we hypothesize that TGFβ2 and HA alongside Tβ4 create a regenerative niche potentiating effective reprogramming of cells into cardiomyocytes. These factors should promote cellular differentiation without driving proliferation. We therefore tested whether alone or together HA, TGFβ2 and Tβ4 induces epicardial cell proliferation. Additional experiments are defining the differentiation pathway triggered by the regenerative cocktail of HA, TGFβ2 and Tβ4. These data are vital for understanding how upstream factors can promote GMT‐induced cardiac regeneration. Support or Funding Information NIEHS R25ES025494