Smooth muscle cells created from patients’ skin cells

Smooth muscle cells created from patients’ skin cells

Scientists have created cells which make up the walls of blood vessels; research could lead to new treatments and better screening for cardiovascular disease.

Cambridge scientists have for the first time created different types of vascular smooth muscle cells (SMCs) – the cells which make up the walls of blood vessels – using cells from patients’ skin. Their research, which was partly funded by the Wellcome Trust, is published yesterday, 15 January, in the journal Nature Biotechnology.

In the UK, one in three of all deaths is due to cardiovascular disease. The vast majority of these are caused by atherosclerosis, a ‘furring up’ and blockage of blood vessels. For patients who are unsuitable for conventional stenting or bypass treatment, one option in the future may be to grow new blood vessels to bypass their own blocked vessels.

Lead author of the research, Dr Sanjay Sinha, Wellcome Trust Intermediate Clinical Fellow at the University of Cambridge said: “This research represents an important step in being able to generate the right kind of smooth muscle cells to help construct these new blood vessels. Other patients who may benefit from new blood vessels include those with renal failure, who need vascular grafts for dialysis.”

For the research, the scientists used embryonic stem cells (or similar cells derived from a patient’s skin sample), which have the potential to form any cell type in the body, known as human pluripotent stem cells (hPSCs). Using hPSCs, they discovered a method for creating high purity vascular smooth muscle. Although blood and cardiac cells from hPSCs have been created before, this is the first time that all the major types of vascular smooth muscle cells have been developed and done so in a system which would be easy to scale up for clinical-grade production.

Vascular smooth muscle cells originate from different tissues in the early embryo, and the scientists were able to reproduce three distinct types of embryonic tissue in the culture dish. Interestingly, these SMCs responded differently to vascular disease causing substances, such as growth factors, depending on which embryonic pathway they had come from. They conclude that differences in embryonic origin may play a part in determining where and when common vascular diseases such as aortic aneurysms or atherosclerosis develop.

Dr Sinha added: “Using this system, we can begin to understand how SMC origin affects development of vascular disease and why some parts of the vasculature are protected from disease.

“Additionally, there are many patients who have a genetic disorder, such as Marfans Syndrome, that affects their vascular smooth muscle cells and leads to premature death and disability. With this research, and using hPSCs generated from patient skin samples, we will be able to generate smooth muscle cells with the genetic abnormality in a culture dish. This type of ‘disease in a dish’ modelling will allow us to understand the disease better and will allow us to screen for new treatments.”

Heterogeneity of embryological origins is a hallmark of vascular smooth muscle cells (SMCs) and may influence the development of vascular disease. Differentiation of human pluripotent stem cells (hPSCs) into developmental origin–specific SMC subtypes remains elusive. Here we describe a chemically defined protocol in which hPSCs were initially induced to form neuroectoderm, lateral plate mesoderm or paraxial mesoderm. These intermediate populations were further differentiated toward SMCs (>80% MYH11+ and ACTA2+), which displayed contractile ability in response to vasoconstrictors and invested perivascular regions in vivo. Derived SMC subtypes recapitulated the unique proliferative and secretory responses to cytokines previously documented in studies using aortic SMCs of distinct origins. Notably, this system predicted increased extracellular matrix degradation by SMCs derived from lateral plate mesoderm, which was confirmed using rat aortic SMCs from corresponding origins. This differentiation approach will have broad applications in modeling origin-dependent disease susceptibility and in developing bioengineered vascular grafts for regenerative medicine.

Scientists from Cambridge University have reported in Nature Biotechnology a breakthrough in turning skin cells into different types of vascular smooth muscle cells.

The new technology may one day lead to the opportunity of growing new blood vessels for patients whose own blood vessels are blocked due to atherosclerosis. The scientists, led by Dr Sanjay Sinha, used embryonic pluripotent stem cells that can be derived from a patient’s skin for their research.

The three different types of vascular smooth muscle cells that were created responded differently when exposed to substances which cause vascular disease. This could be a sign that a different embryonic origin of vascular smooth muscle cells may be a factor in the development of vascular diseases. Sinha and his group want to use their new technique to better understand vascular pathophysiology and explore new treatments.

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