Reprograming of adult fibroblasts into endothelial cells using a single transcription factor for the repair of ischemic tissue.
- Converts to endothelial cells with a single, non-tumorigenic, transcription factor.
- Bypasses a pluripotent stage and avoids the use of potentially tumorigenic stem cells.
Ischemic cardiovascular disease, including coronary artery disease and peripheral artery disease, is the most frequent cause of death in the US. These causes of death are the clinical manifestation of a loss of functional blood vessels. Because endothelial cells are required for the healing of ischemic tissues, there have been many attempts to develop endothelial cells for cell-based therapies. While originally promising, stem cells have had limited clinical application due to inefficient differentiation and tumorigenic concerns. There is currently no established treatment option for repairing damage to cardiac tissue from a heart attack. Efficient and safe production of endothelial cells has the potential to become a treatment option for the nearly 715,000 Americans who have a heart attack each year. In addition, endothelial cells have treatment potential for strokes, diabetic complications and general wound healing.
Isolation of endothelial cells from adult organs for culture and treatment applications is prohibitively challenging. Likewise, differentiating embryonic stem cells or induced pluripotent stem cells to endothelial cells have tumorigenic potential and are inefficiently produced. These limitations inhibit the advanced evaluation of endothelial cells for their therapeutic potential in cardiovascular diseases, stroke, diabetic neurovascular complications, and wound healing. Emory researchers have identified a single transcription factor, with or without being combined with a small molecule epigenetic modifier, that is able to reprogram adult fibroblasts to endothelial cells. This reprogramming approach bypasses a pluripotent stage and avoids the use of stem cells, which have tumorigenic and aberrant differentiation potential. These reprogrammed cells express the common gene and protein markers of endothelial cells and can induce vessel formation in vivo.
Successfully reprogrammed human fibroblasts into endothelial cells can induce vessel formation including vasculogenesis, angiogenesis and arteriogenesis in various animal models including ischemic hind limb mouse models.