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| Scar cells(top) transformed into blood vessels. The proof of transformation is indicated by the red color in the bottom picture. The red is an indicator for CD31, a protein made by blood vessels. |
Cardiovascular scientists from Houston Methodist, Stanford University, and Cincinnati Children’s Hospital teamed up in a joint effort to study fibroblasts, cells that cause scarring. Our bodies are filled with an immense amount of fibroblast. Through their study, the scientists discovered that the fibroblasts can be transformed into endothelium, a cell type that forms the lining of blood vessels. The method first involves polyinosinic:polycytidylic acid (poly I:C), a segment of double-stranded RNA, being introduced to fibroblasts. Poly I:C binds to TLR3(toll-like receptor 3), which fools the fibroblast cell into believing it was attacked by a virus. This resulted in a rearrangement of nuclear chromatin, which allowed genes to be expressed that were once restricted. After rearrangement, the fibroblast was treated with VEGF, Vascular endothelial growth factor, which allowed the fibroblasts to become endothelial cells.
"To our knowledge, this is the first time that trans-differentiation to a therapeutic cell type has been accomplished with a small molecules and proteins," explained chairperson, John Cooke, M.D. Houston Methodist Research Institute Department of Cardiovascular Sciences.
The next step in their research involved taking the transformed fibroblasts and introducing them to immune-deficient mice. The immune-deficient mice had poor blood circulation, however, with the transformed fibroblasts the number of vessels in the limbs of the mice increased, and ultimately 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."
Although procedures like this have been performed, this is the first time a small molecule has been reprogrammed. Research groups were able to generate endothelial cells from infectious viruses, viruses that were programmed to manipulate DNA cells. However, this process involves a more complicated approach. Viruses also have the potential to damage patient’s chromosomes. The small-molecule transformation of cells is a safer approach that will be utilized in clinical trials. The new research also helps our society take one step further into regenerative medicine. The new discovery will definitely help humans who suffer from poor blood circulation and cardiovascular health affects, by improving their condition through the formation of new blood vessels.
Article Related: Fibroblasts - http://ghr.nlm.nih.gov/glossary=fibroblast
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