|Department||Nuffield Department of Clinical Laboratory Sciences|
Stem cell therapies for cardiovascular repair
Heart disease is the major cause of death in the world and the number of patients suffering from heart failure, following a heart attack, is steadily increasing. Stem cell therapies are a promising novel treatment that may reduce the number of patients who later die or suffer from heart failure. However, we still do not fully understand how stem cells work and how they are affected by the disease. Ischaemic heart disease is characterised by the poor supply of blood from the coronary arteries to the myocardium, with the consequence of damaging the heart and causing heart failure in the long-term. There is an unmet clinical need to find alternative therapies as the number of patients requiring heart transplants increases.
To evaluate evidence from randomised trials of stem cells administered to patients following a heart attack.
To understand how endogenous cardiac stem cells support blood vessel formation and how their function is affected by cardiovascular risk factors and disease state.
To develop clinical-grade stem cells or biologics that would support blood vessel formation or reduce fibrosis in the damaged heart.
Stem cell fate decisions: Molecular pathways involved in human myelopoiesis.
The extensive proliferative capacity and the ability to differentiate into multiple cell lineages turn stem/progenitor cells into ideal candidates for successful tissue regeneration and repair. Oxygen tensions can influence stem/progenitor cell self-renewal and differentiation within the bone marrow niche. Oxygen deprivation or hypoxia is also associated with rapid cell growth and aberrant blood vessel formation in cancers and with the death of cardiomyocytes following myocardial infarction. The hypoxia-inducible factors (HIFs) mediate the transcriptional responses to hypoxia in normal tissues and in cancers, having also a pivotal role in integrating physiological and epigenetic effectors. HIFs activate the expression of a number of metabolism-, angiogenesis- and inflammation-related genes, including genes of the ubiquitin-proteasome system (UPS). We have identified novel members of the UPS that are regulated by oxygen tension. The first known function of UPS was the degradation of misfolded, damaged or malfunctioning proteins. However, UPS is also involved in the regulation of biological processes such as inflammation, cell proliferation and DNA repair and its activity is drastically reduced with age. We are particularly interested in understanding the role of the UPS in myeloid progenitor maintenance and differentiation both in health and disease.
Sources of Funding
- BHF 2007-2010
- MRC/BBSRC 2008- 2009; 2010-2011
- NIHR 2010-2015
- BMDA Trust Fund 2012-2013
Dr. Martin-Rendon received her undergraduate degree, MSc and PhD in Genetics from the University of Seville, Spain. She worked as a post-doctoral fellow in the Biochemistry Department, University of Oxford and as a Senior Scientist at Oxford BioMedica Ltd before she joined NHS Blood and Transplant where she leads a research group within Stem Cells and Immunotherapies (SCI) at the John Radcliffe Hospital, Oxford. Dr. Martin-Rendon’s research interests focus on developing stem cell therapies to repair the heart and understanding the molecular mechanisms of stem cell fate decisions such as proliferation and differentiation. She is currently conducting translational and basic research on bone marrow and cardiac progenitors with the aim of improving cell therapies for ischaemic heart disease. Dr. Martin-Rendon is also an editor of the Cochrane Heart Review Group.