Induced Pluripotent Stem Cells Combo Could Yield Much-needed Models to Study Vascular Disease

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A study recently published in STEM CELLS Translational Medicine shows smooth muscle and vascular endothelial cells induced from pluripotent stem cells perform similarly to their naturally evolving counterparts under conditions that mimic hardening of the arteries and other blood vessel diseases.

Brian R. Wamhoff, Ph.D., Co-founder and Head of Innovation at HemoShear Therapeutics

A study recently published in STEM CELLS Translational Medicine shows smooth muscle and vascular endothelial cells induced from pluripotent stem cells perform similarly to their naturally evolving counterparts under conditions that mimic hardening of the arteries and other blood vessel diseases. The finding opens the door to modeling rare vascular diseases necessary for research, as well as assists in screening new drugs and developing personalized cell-based therapies.

Researchers have difficulty studying vascular diseases – those affecting the blood vessels – because of a scarcity of human tissue samples and difficulty in accurately modeling the disease of interest. The potential toxic effects when testing a new drug is another reason why a substitute for real blood vessels is desperately needed.

Recent advances in stem cell biology, however, are beginning to change things. Induced pluripotent stem cells (iPSCs), which can differentiate into various adult human cell types, allow scientists to grow human tissue in the lab for research. Additionally, iPSC lines produced from patients with genetic diseases offer the ability to investigate specific genetic alterations of interest and their effect in disease onset and progression.

Research has already shown that vascular endothelial cells (iECs) and smooth muscle cells (iSMCs) can be created from human iPSCs. (Endothelial cells form the interior lining of a blood vessel while smooth muscle cells reside within the wall of the blood vessel.) However, because these cells are not derived from an intact blood vessel, they represent what is known as “an immature phenotype,” which means they don’t have all the properties of their naturally formed – or “primary” – counterparts.

The STEM CELLS Translational Medicine study, conducted by researchers from HemoShear Therapeutics, Charlottesville, Va., and the University of Cambridge, was designed to learn whether a “co-culture” of iECs grown on one side of a porous membrane and iSMCs on the other side exposed to blood flow as seen in the healthy and diseased blood vessel would come close to mimicking how primary vascular cells function.

“While many studies demonstrate the utility of iECs and iSMCs for vascular applications, none to date have provided a direct comparison of primary to iPSC-derived EC and SMCs,” said Brian R. Wamhoff, Ph.D., co-founder of HemoShear and a principal investigator in the study. “We did this by simulating normal blood flow through both the co-culture of iPSC-derived cells or primary cells and then again by simulating blood flow through them under advanced inflammatory conditions, such as hardening of the arteries and exposure to drug treatments.”

“While we found that the iPSC-derived cells didn’t perform quite as well as the primary cells under normal blood flow conditions, when it came to advanced inflammatory and drug-related conditions, the iPSCs performed very well,” Dr. Wamhoff said. “Thus, we believe this co-culture may have promise for modeling atherosclerosis or other diseases where no primary cells exist or are challenging to procure.”

“Toxicity of drugs to the blood vessels is a major impediment to the development of new therapies,” said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “This research may result in a viable system for modeling rare vascular diseases and testing new therapeutic approaches.”

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The full article, “Exposure of iPSC-derived vascular endothelial and smooth muscle cells in co-culture to hemodynamics induces primary vascular cell-like phenotypes,” can be accessed at: http://www.stemcellstm.com.

About STEM CELLS Translational Medicine: STEM CELLS Translational Medicine (SCTM), published by AlphaMed Press, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes two other internationally renowned peer-reviewed journals: STEM CELLS® (http://www.StemCells.com), celebrating its 35th year, is the world's first journal devoted to this fast paced field of research. The Oncologist® (http://www.TheOncologist.com), also a monthly peer-reviewed publication, entering its 22nd year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. All three journals are premier periodicals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines.

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Chelsea Kekahuna
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