What happens to certain blood vessel stem cells in people with diabetes?
- Type of funding: PhD Studentship
- Grant Holder: Professor Alan Stitt
- Institute: Queen’s University Belfast
- Region: Northern Ireland
- Start date: October 2011
- End Date: September 2014
- Eye Category:
In conditions such as diabetic retinopathy and retinopathy of prematurity, blood vessels in the light-sensitive part of the eye (the retina) degenerate and fail to supply the retina with the oxygen and nutrition it needs. This is called ischaemic retinopathy, and it can lead to severe visual impairment.
Current treatments for most ischaemic retinopathies aren’t good enough and generally focus on the later stages. So there’s an urgent need to explore ways to treat the early stages of vessel damage to prevent the conditions becoming sight-threatening.
Recent evidence suggests that certain blood vessel (vascular) stem cells can be injected into patients to help blood vessel repair. But it’s important to get exactly the right cell type, especially in people with diabetes, as using the wrong ones could make diabetic retinopathy worse.In this project the student was finding out more about blood vessel stem cells in people with diabetes. They focussed on a cell type that has been used in other clinical research, outside the retina. The aim was to gain basic knowledge that could lead to a stem cell therapy for people with diabetic retinopathy.
Analysis of the vasoreparative and anti-inflammatory potential of a myelomonocytic endothelial progenitor cell (EPC) sub-type for treating diabetic retinopathy.
Endothelial progenitor cells (EPCs) represent a small, but critically important population of vascular stem cells circulating in blood. EPCs play a major role in vascular maintenance and regeneration. They also constitute a reliable biomarker of endogenous vascular repair capacity. There has been increasing interest in using EPCs as a cell therapy to promote revascularisation of ischaemic tissues. Ischaemic retinopathies are leading causes of blindness and current treatments for these eye diseases such as pan-retinal laser photocoagulation and vitreoretinal surgery are mainly focused on end-stages of the disease and do not address the primary pathology. While such “cell therapy” is already undergoing clinical trials for heart disease and limb ischaemia, it has not been used in the eye.
EPCs have potential as an alternative and novel treatment for vascular repair and reperfusion of the ischaemic retina, such as occurs in diabetic retinopathy. However there is a pressing need to characterise the precise nature of EPCs since this nomenclature represents a “catch-all” for a range of cell-types with distinct derivation and differentiation potential. Such heterogeneity is problematic because therapy using the “wrong” cell-type delivered into a diseased tissue (such as diabetes) has potential to exacerbate pathology. This is especially true for diabetic retina.
In this studentship, experiments have been designed to evaluate key questions that aid understanding of the nature of EPCs in diabetes. They also address the current hurdles preventing EPC-based therapy for ischaemic retinopathies.The project used complementary in vitro and in vivo approaches and also utilised EPCs from defined patient groups within a translational structure.
In this project, the student, Sarah Chambers, studied a type of cell known as ‘circulating angiogeneic cells’. They can be isolated and injected into patients to help blood vessel repair. The results showed that this type of cell changes what it does depending on the environment it’s in.When they’re exposed to high levels of sugar they are less able to help grow new blood vessels. When they’re compared to circulating angiogenic cells from people without diabetes, the cells from diabetic people have fewer specific markers that mean they can do repairs. They next steps are finding out more about why this is, and how to change it so that people with diabetic retinopathy could potentially be treated with their own blood vessel stem cells.
- Chambers SEJ, O’Neill CL, O’Doherty TM, Medina RJ, Stitt AW. The role of immune-related myeloid cells in angiogenesis. Immunobiology. 2013 Nov;218(11):1370–5.
- Medina RJ, O’Neill CL, O’Doherty TM, Chambers SEJ, Guduric-Fuchs J, Neisen J, et al. Ex vivo expansion of human outgrowth endothelial cells leads to IL-8-mediated replicative senescence and impaired vasoreparative function. Stem Cells. 2013 Aug;31(8):1657–68.
- Stitt AW, Lois N, Medina RJ, Adamson P, Curtis TM. Advances in our understanding of diabetic retinopathy. Clin Sci. 2013 Jul;125(1):1–17.
- J. Medina R, L. O’Neill C, M. O’Doherty T, E.J. Wilson S, W. Stitt. A. A Review of Patents Relating to Therapeutic Angiogenesis Using Endothelial Progenitors and Other Vasculogenesis-Related Cell Types. Recent Patents on Regenerative Medicine. 2012 Oct 1 ;3(1):63–73.
- Medina RJ, O’Neill CL, O', Doherty TM, Wilson SEJ, Stitt AW, et al. Endothelial Progenitors as Tools to Study Vascular Disease, Endothelial Progenitors as Tools to Study Vascular Disease. Stem Cells International. 2012 Mar 15;2012, 2012:e346735.
- O’Neill CL, O’Doherty MT, Wilson SE, Rana AA, Hirst CE, Stitt AW, et al. Therapeutic revascularisation of ischaemic tissue: the opportunities and challenges for therapy using vascular stem/progenitor cells. Stem Cell Res Ther. 2012;3(4):31.