New perspectives of induced pluripotent stem cells

Vascular endothelial cells obtained from IPSC,
open up new possibilities in the treatment of atherosclerosis

LifeSciencesToday based on materials from Harvard Stem Cell Institute:
Take-Home Dialysis Machines? Novel Drugs for Atherosclerosis? The New Potential of Patient-Specific Blood Vessel Cells

Vascular endothelium grown from induced pluripotent stem cells (photo: Garcia-Cardena).

From human induced pluripotent stem cells, scientists at the Harvard Stem Cell Institute have grown cells lining the inner surface of blood vessels – the so–called vascular endothelial cells - and obtained a large amount of information about their functions. Using a unique approach, the researchers induced the differentiation of cells into different functional phenotypes by exposing the surface of the endothelium obtained from induced pluripotent stem cells (iPSCs) to a mechanical force simulating the features of blood flow in different parts of the vascular bed. For example, cells that "felt" a stronger "current" became artery cells, and those that were exposed to a weaker "current" became vein cells.

"We were particularly pleased that these cells mainly respond to biomechanical signals," says study leader Guillermo Garcia–Cardena, PhD. "By exposing cells to the flow that promotes the formation of atherosclerotic plaques, we can direct their differentiation into cells damaged by diseases, for example, atherosclerosis, areas of the cardiovascular system."

Dr. Garcia-Cardegna is already using vascular endothelial cells derived from human iPSCs to simulate the formation of arterial plaques and is looking for potential drugs that could prevent this process.

In addition to the characteristic molecular and structural features of endothelial cells, vascular endothelial cells derived from induced pluripotent stem cells (IPSC-EC) demonstrate phenotypic plasticity, which allows them to mediate leukocyte transmigration and maintain a dynamic barrier. In addition, by various biomechanical or pharmacological stimuli, the development of IPSC-EC can be directed towards either a predisposed to the formation of atherosclerotic plaques, or atheroprotective phenotypes. In general, IPSC-ECS preserve the spectrum of physiological functions of the endothelium and have relevant phenotypic plasticity for studying important features of the cardiovascular pathophysiology of a particular patient (Stem Cell Reports).

He and his colleagues found that human vascular endothelial cells derived from induced pluripotent stem cells retain the ability to perform three important functions of the mature endothelium – to stimulate the development of inflammatory reactions and prevent blood leakage from blood vessels and the formation of blood clots.

The work of Dr. Garcia-Cardegna, published in the journal Stem Cell Reports (Adams et al. Functional Vascular Endothelium Derived from Human Induced Pluripotent Stem Cells), has another promising practical application: its results indicate the potential to reduce the dose of heparin, and possibly completely remove the need for its administration, during renal dialysis and treatment of pulmonary insufficiency, making both much safer.

Traditionally, patients on dialysis are injected with heparin, a powerful drug that prevents blood clotting when it passes through a dialysis machine. While heparin effectively prevents the formation of blood clots, its use is fraught with the development of internal bleeding. In addition, it has antiplastic properties.

"Endothelial cells grown from induced pluripotent stem cells function perfectly as an anticoagulating surface," comments Garcia–Cardegna, associate professor of pathology at Harvard Medical School and Brigham and Women's Hospital. "In the future, we will be able to take a patient's tissue sample, obtain an IPSC, and then cover the extracorporeal device with the patient's own endothelial cells. With such a device, he will be able to go home, as he will no longer need regular injections of heparin."

Portal "Eternal youth" http://vechnayamolodost.ru 26.08.2013