Vascular cell generation could be used to treat vascular disorders

Oct 23 2012

By Piriya Mahendra, medwireNews Reporter

A study in mice has shown that large numbers of vascular endothelial cells (VECs) can be generated from human amniotic fluid-derived cells (ACs).

This finding means that VECs could be used to promote organ regeneration and treat vascular disorders, report Shahin Rafii (Ansary Stem Cell Institute, Weill Cornell Medical College, New York, USA) and colleagues in Cell.

"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," said Rafii in a press statement.

"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."

Previous stem cell strategies have produced unstable VECs that convert to nonvascular cells and do not multiply rapidly in number, which limits their clinical application. Rafii and team circumvented this problem by extracting a large number of VECs during routine amniocentesis of ACs, representing a steady source of cells.

The researchers reprogrammed ACs into mature, functional VECs (rAC-VECs) by enforcing expression of the ETS transcription factor gene (ETV2), Friend Leukemia virus Integration 1 gene (FLI1), and constitutive Ether-à-go-go Related Gene 1 (ERG1) gene, while inhibiting the transforming growth factor beta gene (TGFβ) and silencing nonvascular genes.

The authors note that the resulting rAC-VECs resembled authentic mature endothelial cells in global gene expression, and that when the rAC-VECs were transplanted into regenerating mice livers, they formed functional and stable blood vessels.

"Given that rAC-VECs and ACs could be human leukocyte antigen (HLA) typed, cryopreserved, and publicly banked, these cells could establish an inventory for generating abundant vascular cells for promoting angiocrine-dependent organ regeneration as well as lay the foundation for treating genetically diverse populations of patients with vascular disorders," the team writes.

Rafii remarked: "This major breakthrough will allow the use of endothelial cells for the treatment of numerous vascular disorders and may benefit a myriad of patients."

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