In 2008, scientists from Thomas Jefferson University in Philadelphia, Pennsylvania and the University of Heidelberg, Germany published a study that shows the conversion of bone marrow stem cells into cells that look like heart muscle cells. They cultured rat bone marrow stem cells with heart muscle cells from baby rats and then added two growth factors that are commonly found in developing heart. These growth factors include fibroblast growth factor-2 (FGF-2) and bone morphogen protein-2 (BMP-2). They cultured the bone marrow stem cells with the baby rate heart muscle cells for ten days and added either BMP-2, FGF-2 or FGF-2 + BMP-2. Neither BMP-2 or FGF-2 alone could elicit any significant change in the bone marrow cells, but when FGF-2 and BMP-2 were added together, the caused the bone marrow stem cells to express heart muscle-specific genes.
Transformed bone marrow stem cells made transcription factors like Nkx2.5 and GATA-4. These two transcription factors are expressed in developing heart cells, and the production of these transcription factors in bone marrow stem cells demonstrates that they are differentiating into heart cells. These transformed bone marrow stem cells also produced connexion-43, which is a protein that allows calcium ions to pass from one heart muscle cell to another so that they beat simultaneously. Since heart muscle cells specifically make this protein, it suggests that the bone marrow stem cells are becoming heart cells.
Even more remarkably, the transformed bone marrow stem cells showed calcium-handling proteins and calcium currents that occurred as a result of stimulation. Heart muscle cells spontaneously form calcium currents in response to a flood of calcium ions from the neighboring cells. Heart muscle cells have calcium channels called L-type calcium channels. Particular drugs block these channels, and they are sometimes prescribed to lower blood pressure. The inducible calcium channels in the transformed bone marrow stem cells could be inhibited by these calcium channel blocking drugs, which argues that the calcium currents are due to proteins that are usually expressed in heart muscle cells.
These data argue that bone marrow stem cells can become heart muscle cells. Bone marrow treatments have been used in clinical trials for heart attack patients. However, the ability of bone marrow cells to differentiate into heart muscle cells is limited. Even though there is plenty of evidence that bone marrow stem cells can become heart muscle cells, they appear to do so at a very low-frequency. Therefore, changing bone marrow stem cells into heart muscle cells should greatly increase the therapeutic capacity of these cells. Treatment of human bone marrow stem cells with BMP-2 and FGF-2 might transform bone marrow stem cells into heart muscle cells, which would augment the ability of bone marrow stem cells to treat heart attack patients.