A new approach for generating large numbers of circulatory system cells, known as vascular endothelial cells (VECs), from human amniotic-fluid-derived cells (ACs) is reported in a study published by Cell Press October 18th in the journal Cell. The strategy, which shows promise in mice, opens the door to establishing a vast inventory of VECs for promoting organ regeneration and treating diverse vascular disorders.
"Currently, there is no treatment available for a broad range of patients with vascular diseases, including patients who have suffered heart attack, stroke, lung diseases, trauma, emphysema, or even diabetes and neurological disorders," says senior study author Shahin Rafii of Weill Cornell Medical College. "Replacing injured or dysfunctional endothelial cells with normal cultured endothelial cells could potentially provide for a novel therapy to treat these diseases that afflict millions of patients worldwide."
VECs line the entire circulatory system, including the heart and blood vessels, and they help to control blood pressure, promote the formation of new blood vessels, and support the regeneration and repair of injured organs. A wide range of vascular diseases stem from dysfunctions in VECs, so generating healthy cells for transplantation in patients would represent an attractive treatment strategy. But past stem cell strategies have fallen short: VECs derived from stem cells are unstable and tend to convert to nonvascular cells, and they do not increase rapidly in number, limiting their potential for clinical use.
To overcome these limitations, Rafii and his team developed a safe approach for producing a large number of stable VECs from amniotic cells, which are extracted during routine amniocentesis procedures and thus represent a steady source of cells. To reprogram amniotic cells into mature and functional VECs, called rAC-VECs, the researchers turned specific genes on and off using members of the E-twenty-six family of transcription factors -- proteins that bind DNA and are important for VEC development.
The rAC-VECs resembled human adult VECs in that they expressed the normal set of vascular-specific genes. When rAC-VECs were transplanted into the regenerating livers of mice, they formed stable, normal, and functional blood vessels. "This major breakthrough will allow the use of endothelial cells for the treatment of numerous vascular disorders and may benefit a myriad of patients," Rafii says.
- Michael Ginsberg, Daylon James, Bi-Sen Ding, Daniel Nolan, Fuqiang Geng, Jason M. Butler, William Schachterle, Venkat R. Pulijaal, Susan Mathew, Stephen T. Chasen, Jenny Xiang, Zev Rosenwaks, Koji Shido, Olivier Elemento, Sina Y. Rabbany, Shahin Rafii. Efficient Direct Reprogramming of Mature Amniotic Cells into Endothelial Cells by ETS Factors and TGFβ Suppression. Cell, 2012; DOI: 10.1016/j.cell.2012.09.032
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