Scientists may have discovered a new way to repair damaged tissues after they transformed human scar cells into blood vessel cells.
The method appeared to improve blood flow, oxygenation, and nutrition to areas in need.
Cardiovascular scientists at Houston Methodist, with colleagues at Stanford University and Cincinnati Children’s Hospital, learned that fibroblasts – cells that causes scarring and are plentiful throughout the human body – can be coaxed into becoming endothelium, an entirely different type of adult cell that forms the lining of blood vessels.
“To our knowledge, this is the first time that trans-differentiation to a therapeutic cell type has been accomplished with small molecules and proteins,” said John Cooke, the study’s principal investigator.
“In this particular case, we’ve found a way to turn fibroblasts into ‘shapeshifters’ nearly on command,” said Cooke.
Cooke said the regenerative medicine approach provides proof-of-concept for a small molecule therapy that could one day be used to improve the healing of cardiovascular damage or other injuries.
The new method starts with exposing 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), tricking the cells into reacting as if attacked by a virus.
After treatment with poly I:C, the researchers observed a reorganisation 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.
Cooke and his colleagues reported that about 2 per cent of the fibroblasts were transformed from fibroblasts into endothelial cells, a rate comparable to what other research groups have accomplished using viruses and gene therapy.
But Cooke said preliminary, as-yet-unpublished work by his group suggests they may be able to achieve transformation rates as high as 15 per cent.
In a second part of the study, the scientists introduced the transformed human cells into immune-deficient mice that had poor blood flow to their hind limbs. The human blood vessel cells increased the number of vessels in the mouse limb, improving circulation.
“The cells spontaneously form new blood vessels – they self assemble,” Cooke said.
“Our transformed cells appear to form capillaries in vivo that join with the existing vessels in the animal, as we saw mouse red blood cells inside the vessels composed of human cells,” Cook said.
The study appears in the journal Circulation.