Could stem cell therapy be used to treat sight-loss early?
- Type of funding: Early Career Investigator Award
- Grant Holder: Dr Reinhold Medina Benavente
- Institute: Queen’s University Belfast
- Region: Northern Ireland
- Start date: October 2010
- End Date: September 2013
- Eye Category:
In conditions such as central/branch vein occlusion, diabetic retinopathy and others, blood vessels in the light-sensitive part of the eye (the retina) become damaged. This is known as ‘ischaemic retinopathy’. It means that the retina is not supplied with oxygen and nutrition and can lead to severe sight loss.
Most current treatments for ischaemic retinopathies focus on the later stages, when sight loss has occurred. They don’t tackle the underlying causes. But recent research by the team suggests that certain blood vessel (vascular) stem cells can be injected into patients to help blood vessels to repair themselves.In this project Dr Medina Benevente is studying one type of vascular stem cell to develop the best process of growing and delivering the cells as well as how effective they are as a treatment, in an animal model.
Endothelial progenitor cell therapy for ischaemic retinopathy
Endothelial progenitor cells (EPCs) represent a small, but critically important population of stem cells circulating in blood. EPCs play a major role in vascular maintenance and regeneration, and constitute a reliable biomarker of endogenous vascular repair capacity. Recently, 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. Therefore EPCs have potential as an alternative and novel treatment for vascular repair and reperfusion for ischaemic retinopathies.
This proposal represents an ideal training vehicle for a young scientist developing an independent career. The experiments have been designed to evaluate key questions towards establishing an efficient EPC cytotherapy for ischaemic retinopathies. First, human EPC in vitro expansion capability will be investigated, cell growth dynamics and senescence will be characterised at the molecular level, and ex-vivo stimulation will be tested as a strategy to enhance vasoreparative capacity. Second, cell delivery technique will be optimized in an established murine model of ischaemic retinopathy by assessing delivery routes (systemic vs. intravitreal), cell number (1x103 to 1x105), and different timings for injection (early, intermediate, and late ischaemic phases). Finally, efficiency of EPC cell therapy to repair the ischaemic retina will be evaluated by assessing reduction of hypoxia, increase in vascular density, and changes in cytokine profiles. The biological mechanisms to explain the benefits of an EPC-based autologous cytotherapy will be explored.
Dr Medina Benevente and team have shown that repairing the blood vessels with stem cell therapy works in principle. They are now trying to develop this approach into a treatment that could be used in the clinic.
- Stitt, A. W. et al. The progress in understanding and treatment of diabetic retinopathy. Prog Retin Eye Res 51, 156–186 (2016).
- Rajasekar, P. et al. Epigenetic Changes in Endothelial Progenitors as a Possible Cellular Basis for Glycemic Memory in Diabetic Vascular Complications. Journal of Diabetes Research 2015, e436879 (2015).
- Chambers, S. E. J., O’Neill, C. L., O’Doherty, T. M., Medina, R. J. & Stitt, A. W. The role of immune-related myeloid cells in angiogenesis. Immunobiology 218, 1370–1375 (2013).
- Medina, R. J. et al. Ex vivo expansion of human outgrowth endothelial cells leads to IL-8-mediated replicative senescence and impaired vasoreparative function. Stem Cells 31, 1657–1668 (2013).
- Stitt, A. W., Lois, N., Medina, R. J., Adamson, P. & Curtis, T. M. Advances in our understanding of diabetic retinopathy. Clinical Science 125, 1–17 (2013).
- Liu, Y. et al. Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells. STEM CELLS 30, 1911–1924 (2012).
- O’Neill, C. L. et al. Therapeutic revascularisation of ischaemic tissue: the opportunities and challenges for therapy using vascular stem/progenitor cells. Stem Cell Res Ther 3, 31 (2012).
- Medina, R. J., O’Neill, C. L., O’Doherty, T. M., Wilson, S. E. J. & Stitt, A. W. Endothelial progenitors as tools to study vascular disease. Stem Cells Int 2012, 346735 (2012).
- Medina, R. J. et al. Myeloid angiogenic cells act as alternative M2 macrophages and modulate angiogenesis through interleukin- Mol. Med. 17, 1045–1055 (2011).
- Stitt, A. W. et al. Vascular stem cells and ischaemic retinopathies. Progress in Retinal and Eye Research 30, 149–166 (2011).
- Medina, R. J., Archer, D. B. & Stitt, A. W. Eyes open to stem cells: safety trial may pave the way for cell therapy to treat retinal disease in patients. Stem Cell Res Ther 2, 47 (2011).
- Medina, R. J., O’Neill, C. L., Humphreys, M. W., Gardiner, T. A. & Stitt, A. W. Outgrowth endothelial cells: characterization and their potential for reversing ischemic retinopathy. Invest. Ophthalmol. Vis. Sci. 51, 5906–5913 (2010).