Research paperApplications of nuclear reprogramming and directed differentiation in vascular regenerative medicine
Introduction
The vascular system permeates every organ and tissue of the human body. Acting as the conduit delivering oxygen and nutrients around the body, it is also necessary to allow the translocation of various factors, signals and by-products. Blood vessels consist of endothelial cell (EC) networks, which are often associated with mural cells including smooth muscle cells (SMCs) and pericytes.
The vascular system is divided into arterial and venous portions, in which the vessel architecture and function are distinct. The arterial system carries oxygenated blood to target tissues. It has higher blood pressures and has a higher component of smooth muscle cells underlying the endothelium. The venous system, whose goal is to deliver the deoxygenated blood back to the heart, has developed valves to deal with pressure changes and veins tend to have a larger luminal area in cross section compared to arteries. In addition, the vascular branch has macro- and micro-vascular components, from large vessels such as the aorta to capillary networks in the peripheral regions.
Section snippets
Normal function and pathological aberrations of ECs
Endothelial cells line the innermost surface of blood and lymphatic vessels. Under normal conditions they form a mono-layered structure that provides a semi-selective yet dynamic barrier function between the lumen of the vessel and the surrounding tissues [1]. This permits the controlled passage of factors and cells, such as those of the immune system, from the blood or lymph into the tissue the vessel passes through. It is also responsible for regulating blood flow, vascular tone and vascular
The future: building vessels
In addition to the considerations raised earlier regarding the translation of pluripotent stem cell derived vascular cells to the clinic and for improved disease modelling and drug screening, we must also consider how we can use these cells to generate functional blood vessels for potential transplantation therapies. To do this we would firstly have to consider the heterogenicity of the vascular system to be sure of using the right combination of cell-types, and so it is clear that more work is
Conclusion
Both endothelial and smooth muscle cell dysfunction can lead to a variety of vascular pathologies but the limited renewal capacity of cell lines producing these cell types has impeded research in this area. The availability of pluripotent cell lines and the subsequent establishment of directed differentiation protocols into endothelial and smooth muscle populations have overcome the limitations caused by a finite source of experimental material. Both endothelial and VSMC populations are
Acknowledgements
The work was funded by British Heart Foundation and British Heart Foundation Centre for Regenerative Medicine, Fight for Sight, Robert McApline Foundation and Dinosaur Trust and supported by the Foundation Le Ducq and Cambridge NIHR Biomedical Research Centre.
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