Acute and chronic inflammation is damaging to all cell types and contributes to the pathogenesis of a number of diseases, including cardiovascular disease. “Inflamm-aging” is a chronic, sterile, systemic pro-inflammatory status that occurs during ageing. Senescent cells, which accumulate in tissues with ageing and disease, secrete pro-inflammatory senescence associated-secretory phenotype (SASP) factors contributing to inflamm-aging. Mesenchymal stromal cells or Medicinal signalling cells (MSCs) have a powerful immunomodulatory, anti-inflammatory and reparative/regenerative function.
We hypothesise that: MSCs can target and suppress inflammation and inflamm-aging, thus directly attenuate the damaging effects of inflammation to the cardiovascular system.
1. To elucidate whether MSCs attenuate the damaging systemic effects of inflamm-ageing on human cardiomyocytes and cardiac endothelial cells in vitro. Rotation project and Year 1
2. Characterising senescence and inflamm-aging in healthy and ischaemic muscle from patients with Chronic Limb Threatening Ischemia (CLTI). Year 2
3. To elucidate whether MSCs attenuate the damaging systemic effects of inflamm-ageing in an animal model of Chronic Limb Threatening Ischemia (CLTI). Year 3 and 4 (if 0+4).
Techniques and skills: The student will be trained in a range of cutting-edge in vitro and in vivo techniques. These include primary human cell isolation, generation and maintenance of human cells/iPSCs and iPSC-CMs in co-culture, cell phenotyping using multi-parameter flow cytometry, NGS, multiplex Luminex, immunostaining, confocal and light microscopy and image analysis, in vivo animal models. The student will use the laboratories of Dr. Patel and Prof. Ellison-Hughes as well as the BRC/KCL Core Facilities to carry out the work.