Dr Cédric Ghevaert
In vitro production of platelets for transfusion
Laboratory: Cambridge Blood Centre, NHS Blood and Transplant, Cambridge Biomedical Campus
Departmental Affiliation: Haematology
Cédric Ghevaert graduated from the medical school of the University Libre de Bruxelles in 1997 and subsequently became a fellow of the Royal College of Physicians, London (2000). He specialised in Haematology and became a fellow of the Royal College of Pathologists in 2005. He obtained his PhD in 2008 studying novel antibodies for the treatment of bleeding in neonates in Cambridge. He obtained a personal Intermediate Clinical Fellowship from the British Heart Foundation whilst working in Prof Steve Watson's group at the university of Birmingham in 2009.
He took up the post of Senior Lecturer in Transfusion Medicine at the University of Cambridge in 2010, a post funded by the NHS Blood and Transplant. In addition to his academic post, Dr Ghevaert also works as a Consultant Haematologist for the NHSBT.
Wellcome, MRC, British Heart Foundation, NHS Blood and Transplant, NIHR
Megakaryocytes were produced from human pluripotent stem cells through over expression of 3 key transcription factors TAL1, GATA1 and FLI1. These cells are capable of producing platelets that contain the granules (in red) necessary to perform their clotting function after transfusion. Green= alpha-tubulin, Red=P-selectin, Blue=nuclei.
The main focus of my group’s research is the production of blood cells for human use, namely red cells and platelets. We have developed a particular expertise in the production of these cell types from human pluripotent stem cells using methodologies that are compatible with the production of clinical grade products within the constraints of affordable manufacturing processes. To this end we are combining cellular programming through knowledge and manipulation of transcription fa ctor networks and the creation of 3D biocompatible niches and bioreactors.
As a consultant haematologist for the NHS Blood and Transplant (a partner organisation of the University of Cambridge) I have an expertise recognised world-wide in carrying out first-in-man studies of blood cell survival and recovery in human volunteers. I am the clinical lead for 3 such trials due to take place in the next 5 years on the Cambridge Biomedical Campus.
Cavan Bennett, Amanda Dalby, Amanda Evans, Holly Foster, Nina Herbert, Daniel Howard, Thomas Moreau, Annett Müller, Amanda Niven, Momal Taimoor, Amie Waller.
We are currently entirely reliant on blood donors for the red cells and platelets transfusion we administer to patients who are very anaemic or at high risk of bleeding. Producing these blood cells in the laboratory would take the pressure of the supply chain and would make finding compatible blood for patients with rare blood groups easier. We are developing novel methods to produce red cells and platelets from human stem cells by using key "identity switches" and programming the stem cells to become blood cells. This method generates highly pure cell harvest with large quantities of blood cells to the point that we are now setting up clinical trials to assess these cells in human volunteers.
- Moreau T, Evans AL, Vasquez L, Tijssen MR, Yan Y, Trotter MW, Howard D, Colzani M, Arumugam M, Wu WH, Dalby A, Lampela R, Bouet G, Hobbs CM, Pask DC, Payne H, Ponomaryov T, Brill A, Soranzo N, Ouwehand WH, Pedersen RA, Ghevaert C. Large scale production of platelet forming megakaryocytes from human pluripotent stem cells by a chemically defined forward programming approach. Nat Commun. 2016 Apr 7;7:11208 PMID:27052461
- Guerrero JA, Bennett C, Van der Weyden L, McKinney H, Chin M, Nurden P, McIntyre Z, Cambridge EL, Estabel J, …, Ghevaert C. Gray Platelet Syndrome: Proinflammatory Megakaryocytes and a-granule loss cause myelofibrosis and confer resistance to cancer metastasis. Blood 124(24): 3624-35. PMID:25258341
- Hobbs CM, Manning H, Bennett C, Vasquez L, Severin S, Brain L, Mazharian A, Guerrero JA, Li J, Soranzo,…, Ghevaert C. (2013) JAK2V617F leads to intrinsic changes in platelet formation and reactivity in a knock-in mouse model of essential thrombocythemia. Blood 122:3787-3797. PMCID:PMC3843237
- Ghevaert C, Herbert N, Hawkins L, Grehan N, Cookson P, Garner SF, Crisp-Hihn A, Lloyd-Evans P, Evans A, Balan K, et al. (2013) Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers. Blood 122:313-320. PMCID:PMC3716198
- Albers CA, Paul DS, Schulze H, Freson K, Stephens JC, Smethurst PA, Jolley JD, Cvejic A, Kostadima M, Bertone P,…, Ghevaert C (2012) Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome. Nat Genet 44:435-439, S431-432. PMCID:PMC3428915