Prof Carolyn Carr: We currently have three strands to our research: 1) we are characterising the substrate metabolism of iPS-cardiomyocytes and stimulating oxidative metabolism by culture in 3D on porous scaffolds or in EHTs and by triggering fatty acid metabolism; 2) we are treating cardiac progenitor cells, isolated from the atria, with microRNAs to increase cell survival post transplantation and release of beneficial paracrine factors; 3) with Ipsita Roy, we are encapsulating cytokine-releasing microparticles in porous collagen scaffolds to generate acellular scaffolds for therapy.

Oxford University |

Dr Matt Daniels: My group makes, and apply, genetically encoded tools to study the stem-cell derived cardiomyocyte. This includes bioluminescent calcium (Nat Comm 2016, PMID: 27966527), bioluminescent voltage (Sci Rep 2017, PMID: 28205521), fluorescent calcium combined with optogenetics (PlosONE 2017, PMID: 28379974), and myofilament restricted fluorescent calcium (BioRixv, 2018, tools. I am also a clinical cardiologist working with patients born with inherited or congenital cardiac disease who may be beneficiaries of regenerative cardiology in the future.

Cambridge University |

Dr Gabor Foldes: Gabor works on a Cross-Centre post between the Imperial and Vascular Centres with the aims to develop vascularisation strategies for biomaterial/pluripotent stem cell-derived cardiac patches. This project requires new tissue engineering approaches and scaled-up high-fidelity generation of cardiovascular lineages to investigate whether survival and engraftment of exogenous cells can improve myocardial repair and neovasculogenesis.

Gabor has recently received the MRC Regenerative Medicine Research Grant to generate vascular constructs using human pluripotent stem cells in the therapy of peripheral arterial disease. If successful, this new joint effort between many BHF Centre members including Imperial College, University of Bristol, and the Cell and Gene Therapy Catapult will generate the first clinical product from the Centre.

We welcome any ideas for collaboration on these multi-disciplinary projects.

Imperial College London | 

Prof Paolo Madeddu: My team works on cardiovascular regeneration with a focus on gene therapy and cellular (pericyte) therapy to contrast age-related cardiovascular disease. We have also major grants on tissue engineering for treatment of congenital heart disease and a BHF program grant investigating the remodelling effect of diabetes on the bone marrow niche with implications for peripheral vascular complications. I am named collaborator in a new MRC grant to Foldes and also collaborate with Costanza Emanueli and Marc Dumas at the Imperial College. My involvement in the BHF CRM is twofold: (1) To identify and exploit the molecular mechanism underpinning cardiac pericytes commitment to coronary arteriogenesis and (2) To provide pericytes feeding the in vivo comparative study of cell therapy in a swine model of MI.

University of Bristol | 

Dr Annette Meeson: My research focuses on the duration and impact of IDC on native cardiac derived stem cells. In addition I am interested in furthering the understanding of healthy cardiac stem cell biology throughout cardiogenesis and maturation.

Newcastle University |

Prof Philippe Menasche: Our work is focused on a translational program geared at the clinical use of cardiovascular progenitor cell-derived extracellular vesicles (EVs) in patients with severe heart failure. The ongoing experiments entail testing methods for a large-scale GMP-compliant cell expansion followed by purification of the conditioned medium by a clinically usable technique and development of in-process quality controls. Enclosed are two recent papers summarizing our clinical experience with the transplantation of ESC-derived cardiovascular progenitor cells and our preclinical experience with iPSC-derived EVs.


Dr Stephen Niederer: Dr Steven Niederer's research is characterised by the use of multi-scale and multi-physics computational models of the heart to investigate fundamental physiological questions and gain insight into patient pathologies and treatments. This work includes the development of novel methods for integrating and interpreting patient data, evaluating new medical devices using computational modelling and developing patient specific models. His research is highly interdisciplinary, working closely with imaging scientists, basic researchers and cardiologists with a strong focus on clinical translation.

Kings College London |

Dr Michela Noseda: We previously found that intramyocardial injection of cardiac progenitor cells (CPCs) at time of ischemia improves cardiac function 12 weeks later. Given poor long-term engraftment in our studies and many others’, the consensus is that early paracrine effects are the probable cause of the benefits observed, including direct effects on cardiomyocytes but also macrophages as key players in the response to injury.

The major advancements of our team working on paracrine circuits for heart repair by cardiac stem cells focus on the protective effects on cardiomyocytes and macrophages. Using human iPS-derived cardiomyocytes as a platform, we found that conditioned-media from cardiac progenitors determines protection from cell death and apoptosis triggered by different stresses. Our complementary studies demonstrate that progenitors’ paracrine effects include disruption of the pro-inflammatory (“M1”) programme induced by GM-CSF/LPS/IFN, and promoting instead the formation of anti-inflammatory (“M2”) macrophages. We are using single cell technologies as well as high-throughput approaches to define and validate candidate factors mediating the specify effects described above.

From a quantitative and qualitative point of view, the magnitude of protection and the anti-inflammatory effects do not just merely provide a mechanistic implication for the improvement in cardiac function determined by intra-myocardial injection of progenitors at time of myocardial infarction. These findings allow us to envision cell-free therapies based on delivery of the factors mediating cardiomyocytes cell death prevention and immunomodulation as well as adjuvants to other therapies including as a pro-survival treatment of iPS-derived cardiomycoytes to be used as a cell therapy.

Imperial College London |

Prof Amer Rana: Developmental and disease modelling of vascular identities and regeneration using human pluripotent stem cells and animal models. We have a particular focus on understanding and modelling the pulmonary and cardiac vasculature including the endocardium and it’s derivatives and in modelling pulmonary vascular disease (pulmonary hypertension). Through these models we aim to improve vascular regeneration post-MI, develop more sophisticated models for cardiovascular and cardiopulmonary drug screening and are keen to collaborate on in vitro and in vivo 3D tissue replacement models.

Cambridge University | 

Prof Anna Randi: The Randi laboratory investigates the transcriptional pathways that regulate endothelial homeostasis, angiogenesis and lineage identity (Birdsey et al, Developmental cell 2015; Shah et al, Nature Communications 2017; Dufton et al, Nature Communications 2017). We also investigate vascular diseases using circulating human endothelial progenitors (BOEC/ECFC) (Starke et al, Blood 2013; Paschalaki et al, Stem Cell 2013); these cells have stem cell properties and are a promising new avenue for regenerative medicine. The two areas of interest are combined in the project supported by the BHF Centre for vascular regeneration (CVR), where we will carry out genome-wide studies to identify lineage-specific transcriptional and epigenetic pathways in BOEC/ECFC, to be exploited for regenerative medicine approaches.

Imperial College London | 

Dr Gavin Richardson: Cellular senescence is defined as the irreversible loss of division potential in somatic cells. While senescence can be a potent anti-tumour mechanism recent studies have indicated that it is a major contributor to age-dependent tissue dysfunction. We have demonstrated that within the cardiomyocyte population there is an age dependent increase in senescence which contributes to impaired regenerative potential and myocardial remodelling. We are now testing the potential of targeting this senescent cell population in order to revitalise the myocardium in aged and disease hearts.

Newcastle University |

Prof Nadia Rosenthal: We have described novel signaling pathways responsible for the regenerative action of insulin-like growth factor-1 (IGF-1) in skeletal and cardiac muscle. We have redefined cardiac cell composition, and uncovered a role for IGF-1 in orchestrating the tissue repair process through modulation of both innate and adaptive immune cells to improve immune response to myocardial infarction. 

Imperial College London |

Prof Johan Hyllner / Dr Michaela Sharpe: The Cell and Gene Therapy Catapult is a centre of excellence in innovation, with the core purpose of building a world-leading cell and gene therapy sector in the UK as a key part of a global industry. Supported by Innovate UK, our mission is to drive the growth of the industry by helping cell and gene therapy organisations across the world translate early stage research into commercially viable and investable therapies. Many companies in the cell and gene therapy industry start in academia and we work with organisations such as the BHF bringing expertise, such as product development, product safety and commercialisation, to tackle the challenges that may be faced in the development of cell and gene therapies.

Cell Therapy Catapult | | 

Other Collaborators

Prof Raimondo Ascione
Prof Costanza Emanueli
Prof Jorge Ferrer
Dr Alexander Lyon
Dr Guy Macgowan
Dr Prakash Punjabi
Prof Sanjay Sinha
Prof Ken Suzuki
Prof Andrew Trafford