Dr Fiona Lewis-McDougall

Profile

Dr 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 recently joined the Centre for Microvascular Research at the 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.

Research

Group 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:

1. Influence of donor age/disease on iPSC potential
IPSCs 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.

2. Therapeutic potential of iPSC-cardiac progenitor cells for cardiac repair
The 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.

3. Extracellular vesicles as mediators of cardiac repair and regeneration
In 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)

Key Publications

• Podaru M, Fields L, Kainuma S, Ichihara Y, Hussain M, Ito T, Kobayashi K, Mathur A, D’Acquisto F, Lewis-McDougall F, Suzuki K. Reparative macrophage transplantation for myocardial repair: a refinement of bone marrow mononuclear cell-based therapy. Basic Res Cardiol. 2019;114:34
• Lewis-McDougall FC, Ruchaya PJ, Domenjo-Vila E, Teoh TS, Cottle BJ, Clark JE, Punjabi PP, Awad W, Torella D, Tchkonia T, Kirkland JL, Ellison-Hughes GM (2019).  Aged-senescent progenitor cells contribute to impaired heart regeneration. Aging Cell;18(3):e12931
• Kobayashi K, Ichihara Y, Sato N, Umeda N, Fields L, Fukumitsu M, Tago Y, Ito T, Kainuma S, Podaru M, Lewis-McDougall FC, Yamahara K, Suzuki K (2019). On-site fabrication of bi-layered adhesive mesenchymal stromal cell-dressings for the treatment of heart failure. Biomaterials;  209:41-53
• Kobayashi K, Ichihara Y, Tano N, Fields L, Murugesu N, Ito T, Ikebe C, Lewis FC, Yashiro K, Shintani Y, Uppal R, Suzuki K (2018). Fibrin glue-aided, instant epicardial placement enhances the efficacy of mesenchymal stromal cell-based therapy for heart failure. Sci. Rep; 8:9448. 
• Lewis FC, Deva Kumar S, Ellison-Hughes GM (2017). Non-invasive strategies for stimulating endogenous repair and regenerative mechanisms in the damaged heart. Pharmacol. Res; 127: 33-40.
• Agley CC*, Lewis FC*, Jaka O, Lazarus NR, Velloso C, Ellison-Hughes GM, Francis-West P, Harridge SDR *joint first author (2017). Active GSK3β and an intact beta-Catenin TCF complex are essential for the terminal differentiation of human myogenic progenitor cells. Sci. Rep; 7(1):13189.
• Vicinanza C, Aquila I, Scalise M, Cristiano F, Marino F, Cianflone E, Mancuso T, Sacco W, Lewis FC, Couch L, Shone V, Torella A, Smith A, Terracciano C, Britti D, Veltri P, Indolfi C, Nadal-Ginard B, Ellison-Hughes GM, Torella D (2017). Adult Cardiac Stem Cells are Multipotent and Robustly Myogenic: c-kit Expression is Necessary but not Sufficient for their Identification. Cell Death Differ. 24(12):2101-2116.
• Lewis FC, Henning BJ, Shone V, et al. (2017). Transplantation of Allogeneic PW1^pos/Pax7^neg Interstitial Cells (PICs) Enhance Endogenous Repair of Injured Porcine Skeletal Muscle. JACC Basic Transl. Sci. 
• 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. Stem Cell Res. Ther. 8:158.
• Smith AJ, Lewis FC, Aquila I, et al. (2014). Isolation and characterisation of resident endogenous c-kit-positive cardiac stem cells (eCSCs) from the adult mouse and rat heart. Nat. Protoc. 7: 1662-16681. 
• Lewis FC, Henning BJ, Marazzi G, et al. (2014). Porcine skeletal muscle-derived multipotent PW1^pos/Pax7^neg Interstitial Cells: Isolation, characterization and long-term culture. Stem Cells Transl. Med. 3:1-11.
• Torella D, Ellison GM, Torella M, et al. (2014). Carbonic Anhydrases Activation is Associated with Worsened Pathologic Remodeling in Human Ischemic Diabetic Cardiomyopathy. J. Am. Heart Assoc. 3: e000434
• Bryan N, Lewis FC, Stanley C, et al. (2013). Evaluation of a Novel Non-Destructive Catch and Release Technology for Harvesting Autologous Adult Stem Cells. PLOS ONE. 8: e53933. 
• 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.  Cell Regeneration. 1:6.

Collaborators

Internal
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)