Transforming Scar Cells into Blood Vessels

Cardiovascular scientists at Houston Methodist (Texas, USA) lead a team that coaxes fibroblasts — cells that causes scarring and are plentiful throughout the human body — into becoming endothelium, an entirely different type of adult cell that forms the lining of blood vessels.  John Cooke and colleagues utilized a novel small-molecule and protein therapy to achieve trans-differentiation to a therapeutic cell type. The team exposed fibroblasts to poly I:C (polyinosinic:polycytidylic acid), a small segment of double-stranded RNA that binds to the host cell receptor TLR3 (toll-like receptor 3).  After treatment with poly I:C, the researchers observed a reorganization of nuclear chromatin, allowing previously blocked-off genes to be expressed. The fibroblasts were then treated with factors, such as VEGF, that are known to compel less differentiated cells into becoming endothelial cells.  These transformed cells self-assembled into vessels that improved blood flow.   Submitting that: “This study suggests that manipulation of innate immune signaling may be generally used to modify cell fate,” the study authors submit that: “[this] is a first step toward development of a small molecule strategy for therapeutic transdifferentiation for vascular disease.”