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Amniotic Fluid Cells Reprogrammed to Endothelial Cells

Human amniotic fluid cells can be reprogrammed directly into transplantable vascular endothelial cells, bypassing pluripotency.

A new report in Cell from Shahin Rafii, M.D. and colleagues at Weill Cornell Medical College demonstrates direct reprogramming of human amniotic fluid-derived cells into functional vascular endothelial cells.  Prior work from Dr. Rafii’s group found that hESCs and iPSCs could be converted to induced vascular endothelial cells (iVECs), but these are unstable and proliferate poorly.  This allowed the investigators to identify several key transcription factors that were expressed during the differentiation of hESCs into iVECs.  Although ectopic expression of these factors could not overcome all the problems with the original iVECs, using them on amniotic fluid-derived cells (ACs) resulted in VECs that were readily expandable to a clinically relevant scale and could produce functional blood vessels in mice.  In addition, these reprogrammed AC-VECs, or rAC-VECs, acquire the instructive tissue-specific attributes of endothelial cells, endowing them with the capacity to support abundant expansion of human hematopoietic stem cells that could be used for bone marrow transplantation.  A key advantage of AC-VECs as a source of transplantable vascular cells is that human ACs are routinely cultured after amniocentesis for diagnostic purposes during pregnancy, and thus are readily available.  Further, they can also be easily HLA typed for immune matching, cryopreserved and banked, making them an accessible potential cellular source for transplants in the future to treat a wide variety of patients with vascular and hematological disorders.  This research was funded in part by NYSTEM contracts C024180, C026438, C026878.

GinsbergM, JamesD, DingBS, NolanD, ButlerJM, SchachterleW, PulijaalVR, RosenwaksZ, ShidoK, ElementoO, RabbanySY, and Rafii S.  Efficient direct reprogramming of mature human amniotic cells into endothelial cells by ETS factors and TGFb suppression.  Cell, October 18th, 2012.

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Human amniotic fluid cells can be reprogrammed directly into transplantable vascular endothelial cells, bypassing pluripotency.