Dr Fiona Lewis-McDougallSenior Lecturer in Myocardial Repair and RegenerationCentre: Microvascular Research Email: f.lewis@qmul.ac.uk Telephone: +44(0) 20 7882 8238Website: https://www.centre-for-microvascular-research.com/lewis-mcdougall-labProfileResearchPublicationsCollaboratorsProfileDr Fiona Lewis-McDougall completed her undergraduate studies at the University of Liverpool (Anatomy and Human Biology) and obtained her PhD at the UK Centre for Tissue Engineering, University of Liverpool. Subsequently, Fiona completed her post-doctoral research at the Centre for Stem Cells and Regenerative Medicine at King’s College London. She joined the Centre for Microvascular Research at the William Harvey Research Institute (WHRI) as a lecturer in myocardial repair and regeneration. Fiona is now establishing her own research group to investigate the effect of ageing on induced pluripotent stem cells regenerative potential in cardiovascular disease.ResearchGroup members Researcher/Staff: Dr Alia Hafiz Abbas Gasim; Dr Hanin Alyamani Summary Cardiovascular disease is one of the main causes of death in the UK and worldwide. At present no widely available, restorative option exists therefore new strategies are required to identify a safe and efficient way of treating heart failure. In recent years, stem cells have emerged as a potentially valuable tool for repair of damaged hearts and a breakthrough discovery in 2006 identified that stem cells could be generated from a patient’s own skin cells, termed induced pluripotent stem cells (iPSCs). IPSCs have gained increasing recognition given their extensive differentiation capacity, the absence of ethical issues surrounding their use, autologous nature and low immunogenicity. Their therapeutic potential has been demonstrated in studies where progenies of iPSCs when delivered into infarcted hearts improved cardiac function. Fiona’s research primarily focuses on understanding the effect of ageing on stem cell regenerative potential for cardiac repair and regeneration, she is currently pursuing a number of major research themes:Influence of donor age/disease on iPSC potentialIPSCs have been successfully generated from different aged donors however evidence suggests that aged cells generate iPSCs at lower efficiency and may have deteriorated functions making them unsuitable for clinical application. Aging is determined not only by chronological age but also by health condition therefore rigorous testing of iPSCs derived from aged, heart disease patients is required to provide a clear indication on their suitability for clinical application. Identification of key ageing molecular signatures and their association with cellular reprogramming will provide a way to select optimal cells for cardiac regenerative therapies. Therapeutic potential of iPSC-cardiac progenitor cells for cardiac repairThe optimal iPSC progeny for cardiac repair is currently unknown and to date the majority of studies have focused on generating fully differentiated iPSC-cardiomyocytes. While this approach has shown some promise, a major drawback is that only a single replacement cell type is delivered to the heart furthermore iPSC-cardiomyocytes display an immature phenotype and their integration with the host myocardium often leads to arrhythmias. As endogenous cardiac progenitor cells (eCPCs) have been widely reported to possess reparative characteristics the generation of human iPSC-CPCs, offers an alternative source of renewable precursors where isolation of resident CPCs is not feasible. Given that there is currently much discussion regarding the cardiac regenerative capacity of c-kit+ eCPCs, which is largely based on observations using rodent models, we will directly compare human c-kit+ eCPCs and iPSC-CPCs isolated from the same donors to provide vital information and address the therapeutic potential of this population. Extracellular vesicles as mediators of cardiac repair and regenerationIn recent years, extracellular vesicles (EVs) have been identified as both biomarkers and therapeutic agents, with evidence to suggest that they exert protective effects by transferring their contents to rescue injured neighbouring cells. A therapeutic source of EVs for the treatment of heart disease has yet to be identified. To address this, we are exploring different sources of EVs as mediators of cardiac repair and aim to identify the mechanisms by which they exert their regenerative effects. Memberships / Awards Young Investigator Award for best poster presentation at the Biomedical Basis of Elite Performance - Nottingham, UK (March 2016) Young Investigator Award for best oral presentation at the 50th International Congress of European Society for Surgical Research - Liverpool, UK (June 2015) Oral Presentation Award at the Alternative Muscle Club Meeting - London, UK (July 2016) 6th Annual Alliance for Healthy Aging Conference Travel Award - Newcastle UK (October 2015) Publications Ruchaya PJ, Lewis-McDougall FC, Sornkarn N et al. (publicationYear). Transplantation of Skeletal Muscle-Derived Sca-1+/PW1+/Pax7− Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction. nameOfConference DOI: 10.3390/cells11244050 QMRO: https://qmro.qmul.ac.uk/xmlui/handle/123456789/83441 Smith AJ, Ruchaya P, Walmsley R et al. (publicationYear). Receptor tyrosine kinase inhibitors negatively impact on pro-reparative characteristics of human cardiac progenitor cells. nameOfConference DOI: 10.1038/s41598-022-13203-3 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/79051 Suzuki K, Ito T, Lewis F (publicationYear). Epicardial Placement of Fibrin Sealant Film-incorporating Human Mesenchymal Stromal Cells for the Treatment of Heart Failure: Towards Clinical Translation and Mechanistic Implication. nameOfConference DOI: 10.1016/j.ymthe.2021.04.018 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/71498 Ito T, Shintani Y, Fields L et al. (publicationYear). Cell barrier function of resident peritoneal macrophages in post-operative adhesions. nameOfConference DOI: 10.1038/s41467-021-22536-y QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/71369 Podaru MN, Fields L, Kainuma S et al. (2019). 2419Reparative macrophage transplantation for myocardial repair: a refinement of bone marrow mononuclear cell-based therapy. ESC DOI: 10.1093/eurheartj/ehz748.0167 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/67360 Podaru MN, Fields L, Kainuma S et al. (2019). Reparative macrophage transplantation for myocardial repair: a refinement of bone marrow mononuclear cell-based therapy. European Society of Cardiology DOI: doi QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/66259 Podaru M-N, Fields L, Kainuma S et al. (2019). Abstract 718: Reparative Macrophage Transplantation for Myocardial Repair: A Refinement of Bone Marrow Mononuclear Cell-Based Therapy. AHA DOI: 10.1161/res.125.suppl_1.718 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/66641 Podaru M-N, Fields L, Kainuma S et al. (2019). Reparative Macrophage Transplantation for Myocardial Repair: A Refinement of Bone Marrow Mononuclear Cell-Based Therapy. American Heart Association DOI: doi QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/68760 Suzuki K, Podaru M, Fields L et al. (publicationYear). Reparative Macrophage Transplantation for Myocardial Repair: A Refinement of Bone Marrow Mononuclear Cell-Based Therapy. nameOfConference DOI: 10.1007/s00395-019-0742-1 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/58979 Kobayashi K, Ichihara Y, Sato N et al. (2019). On-site fabrication of Bi-layered adhesive mesenchymal stromal cell-dressings for the treatment of heart failure. nameOfConference DOI: 10.1016/j.biomaterials.2019.04.014 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/57098 Lewis‐McDougall FC, Ruchaya PJ, Domenjo‐Vila E et al. (2019). Aged‐senescent cells contribute to impaired heart regeneration. nameOfConference DOI: 10.1111/acel.12931 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/56121 Kobayashi K, Ichihara Y, Sato N et al. (2018). On-Site, Instant Production of Bi-Layered Bio-Dressing Incorporating Mesenchymal Stromal Cells for the Treatment of Heart Failure. AHA DOI: doi QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/66815 Kobayashi K, Ichihara Y, Tano N et al. (publicationYear). Fibrin Glue-aided, Instant Epicardial Placement Enhances the Efficacy of Mesenchymal Stromal Cell-Based Therapy for Heart Failure. nameOfConference DOI: 10.1038/s41598-018-27881-5 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/41023 LEWIS F, Cottle BJ, Shone V et al. (publicationYear). Transplantation of Allogeneic PW1pos/Pax7neg Interstitial Cells (PICs) Enhance Endogenous Repair of Injured Porcine Skeletal Muscle. nameOfConference DOI: 10.1016/j.jacbts.2017.08.002 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/25581 Ellison-Hughes GM, Lewis FC (2017). Progenitor Cells from the Adult Heart. nameOfConference DOI: 10.1007/978-3-319-56106-6_2 QMRO: qmroHref LEWIS F, Agley C, Jaka O et al. (2017). Active GSK3β and an intact β-catenin TCF complex are essential for the differentiation of human myogenic progenitor cells. nameOfConference DOI: 10.1038/s41598-017-10731-1 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/25483 LEWIS F, Deva Kumar S, Ellison-Hughes GM (2018). Non-invasive strategies for stimulating endogenous repair and regenerative mechanisms in the damaged heart. nameOfConference DOI: 10.1016/j.phrs.2017.08.016 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/42603 Vicinanza C, Aquila I, Scalise M et al. (2017). Adult Cardiac Stem Cells are Multipotent and Robustly Myogenic: c-kit Expression is Necessary but not Sufficient for their Identification. nameOfConference DOI: 10.1038/cdd.2017.130 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/25009 Henning BJ, Lewis FC, Shone V et al. (2017). Skeletal muscle-derived interstitial progenitor cells (PICs) display stem cell properties, being clonogenic, self-renewing and multi-potent in vitro and in vivo.. nameOfConference DOI: 10.1186/s13287-017-0612-4 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/24877 Attias J, Bieles J, Carvil P et al. (2017). Altitude exposure and increased heart rate: the role of the parasympathetic nervous system. nameOfConference DOI: 10.1113/JP274220 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/24384 Smith A, Wright K, Lewis F et al. (2016). P44 Tyrosine kinase inhibitor cardiotoxicity and cardiac stem cells. nameOfConference DOI: 10.1136/heartjnl-2016-310696.48 QMRO: qmroHref Lewis FC, Teoh T, Domenjo-Vila E et al. (2016). Canonical wnt signaling reverses the 'aged/senescent' human endogenous cardiac stem cell phenotype. American Heart Association DOI: doi QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/24587 Smith AJ, Lewis FC, Aquila I et al. (2014). Isolation and characterization of resident endogenous c-Kit+ cardiac stem cells from the adult mouse and rat heart. nameOfConference DOI: 10.1038/nprot.2014.113 QMRO: qmroHref Lewis FC, Henning BJ, Marazzi G et al. (2014). Porcine Skeletal Muscle‐Derived Multipotent PW1pos/Pax7neg Interstitial Cells: Isolation, Characterization, and Long‐Term Culture. nameOfConference DOI: 10.5966/sctm.2013-0174 QMRO: qmroHref Torella D, Ellison GM, Torella M et al. (2014). Carbonic Anhydrase Activation Is Associated With Worsened Pathological Remodeling in Human Ischemic Diabetic Cardiomyopathy. nameOfConference DOI: 10.1161/jaha.113.000434 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/71987 Ellison GM, Smith AJ, Waring CD et al. (2014). Adult Cardiac Stem Cells: Identity, Location and Potential. nameOfConference DOI: 10.1007/978-1-4614-9569-7_4 QMRO: qmroHref Bryan N, Lewis FC, Bond D et al. (2013). Evaluation of a Novel Non-Destructive Catch and Release Technology for Harvesting Autologous Adult Stem Cells. nameOfConference DOI: 10.1371/journal.pone.0053933 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/71988 Lewis F, Henning B, Sassoon D et al. (2013). Identification and characterisation of multipotent porcine PW1+/Pax7- skeletal muscle-derived interstitial cells (PICs). nameOfConference DOI: doi QMRO: qmroHref Lewis FC, Bryan N, Hunt JA (2012). A feeder-free, human plasma-derived hydrogel for maintenance of a human embryonic stem cell phenotype in vitro. nameOfConference DOI: 10.1186/2045-9769-1-6 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/72325 Lewis FC, Rhodes NP, Hunt JA (2011). A novel, feeder free, autologous system for maintenance of human embryonic stem cell phenotype. nameOfConference DOI: doi QMRO: qmroHref CollaboratorsInternal Prof Ken Suzuki (WHRI) Prof Andrew Tinker (WHRI) Prof Mauro Perretti (WHRI) External Mr Wael Awad (Barts NHS Trust) Dr Georgina Ellison (King’s College London, UK) Prof Sian Harding (Imperial College London) Back to top