Researchers at Harvard Medical School and the Harvard School of Dental Medicine have found that by mimicking a rare genetic disorder in a dish, they can drive a mature cell back into an adult stem cell-like stage. These stem cells were able to differentiate into various cell types, both in culture and in animal models.
“It's important to clarify that these new cells are not exactly the same as mesenchymal stem cells from bone marrow,” notes Damian Medici, Ph.D., an instructor of medicine at Harvard Medical School and Beth Israel Deaconess Medical Center. “There are some important differences. However, they appear to have all the potential and plasticity of mesenchymal stem cells.”
The findings appeared November 21 online in Nature Medicine. The paper is titled “Conversion of vascular endothelial cells into multipotent stem-like cells.”
Fibrodysplasia ossificans progressiva (FOP), which affects fewer than 1,000 people worldwide, is a genetic disease in which acute inflammation causes soft tissue to morph into cartilage and bone. Dr. Medici found that unlike normal skeletal tissue, the pathological cartilage and bone cells from these patients contained biomarkers specific for endothelial cells.
This led him to question whether or not the cartilage and bone growing in soft tissues of FOP patients had an endothelial origin. Dr. Medici’s team transferred the mutated gene that causes FOP into normal endothelial cells. The endothelial cells converted into a cell type nearly identical to mesenchymal stem cells that could differentiate into bone, cartilage, muscle, fat, and nerve cells.
Further experimentation showed that instead of using the mutated gene to induce transformation, endothelial cells could be incubated with either one of two specific proteins (growth factors TGF-beta2 and BMP4). The cellular interactions of these growth factors mimicked the effects of the mutated gene.
Dr. Medici reports that he was able to take these reprogrammed cells and coax them into developing into a group of related tissue types in both culture dishes and animal models.