TGF-beta stimulating bone marrow to cardiac in vitro

Yamaguchi, Japan -

The ability of various mesenchymal stem cell populations and CD34 stem cell populations to help in stimulation of cardiac regeneration is a current belief by many investigators. Although some positive in vivo data have been generated with purified mesenchymal populations, as well as bone marrow stem cells, little is known about the molecular mechanisms of differentiation.

For example, how does the injured myocardium actually induce the undifferentiated stem cells that are injected intravenously or intracoronarily actually "instruct" the stem cells to differentiate into cardiac tissue? We do know that gradients of factors such as SDF-1 are important in homing of stem cells and that injured hearts make SDF-1 and VEGF, however we do not know the factors that actually are involved in the differentiation process.

In a recent study (Li et al. TGF-beta induces the differentiation of bone marrow stem cells into immature cardiomyocytes. Biochem Biophys Res Commun. 2007 Dec 22 ) the question of bone marrow to cardiomyocyte differentiation was addressed.

It was demonstrated that growing bone marrow stem cells in the presence of TGF-beta 1, would induce morphological differentiation of the stem cells into cardiomyocyte-like cells. These cells expressed cardiac-specific transcription factors such as GATA-4 and NKx-2.5. Additionally, markers such as cardiac myosin, troponin, and atrial natriuretic peptide were detected. By day 28 of culture the calcium flux was relatively weak and spontaneous beating had dissipated.

It will be interesting to combine this in vitro differentiation approach with other agents such as histone deacetylase inhibitors which have been previously demonstrated to increase expression of some markers of cardiomyocytes.