Rebecca Griffiths specialises in Ageing of human haematopoietic stem cells and their niche.

Stem cell maintenance is vital for organ homeostasis and longevity. Haematopoietic stem cells (HSCs) are the most primitive cells in the haematopoietic system and reside in specialised niches in the bone marrow. The bone marrow becomes the main site for HSC maintenance and blood production after birth. It is the site in which massive blood production – lineage commitment, proliferation and differentiation - takes place whilst the HSC pool is maintained. The non-haematopoietic cells such as osteoblasts, endothelial cells, fibroblasts, neurons and adipocytes are present within the niche and can be considered as stromal cells. The specific input of each cell or combination of cells makes up a unique microenvironment which is optimal for HSC and bone maintenance, or progenitor lineage commitment, proliferation and differentiation.

Ageing is correlated to an increased susceptibility to infectious diseases and autoimmune conditions due to failings in the adaptive and innate immune systems.The majority of HSC and HSC niche research, particularly research focused on ageing, is carried out in mice and HSC transplantation studies. 

I am investigating how ageing affects HSCs and other bone marrow niche stem cells in humans.

Using fresh samples of bone marrow, I will isolate the HSCs and non-haematopoietic stem cells from the bone marrow niche and define them. By comparing the bone marrow stem cells from younger and older bone marrow samples we aim to pinpoint the differences in molecular drivers which can be targeted for therapeutics.

Rebecca was previously part of the NIHR Blood and Transplant research team in the UK developing the first in-man Clinical Trial of cultured red blood cells for transfusion from waste blood products.

Human haematopoietic stem cells are isolated from peripheral blood and are cultured, in vitro, for 3 weeks until they differentiate into mature red blood cells. Rebecca was focussed on understanding the differentiation and maturation of erythroid stem cells to mature red blood cells. Her work has led to identification of novel autophagic vesicles on maturing red blood cells that act to both remove organelles and reduce plasma membrane. Subsequent studies in patients with damaged and dysfunctional spleens, such as in Sickle Cell Disease (SCD), found elevated levels of red cells exposing these vesicles. Transfer to clinical practice is ongoing with development of an apheresis machine that removes these vesicles from the circulation.

Rebecca was also involved in developing the first adult human immortalised erythroid cell line that can differentiate into mature red blood cells. These cell lines will provide a safely transfusible red cell product that can be tailored for difficult to transfuse patients. 

Key Publications

​Trakarnsanga K, Griffiths RE, Wilson MC, et al. An immortalized adult human erythroid line facilitates sustainable and scalable generation of functional red cells. Nat Commun. 2017;8:14750.

Mankelow TJ*, Griffiths RE*, Trompeter S, Flatt JF, Cogan NM, Massey EJ and Anstee DJ. The ins and outs of reticulocyte maturation revisited: the role of autophagy in sickle cell disease. Autophagy 2016 Mar 3;12(3):590-1 *Joint first authors

Mankelow TJ*, Griffiths RE*, Trompeter S, Flatt JF, Cogan NM, Massey EJ, Anstee DJ. Autophagic vesicles on mature human reticulocytes explain phosphatidylserine positive red cells in Sickle Cell Disease. Blood. 2015 Oct 8;126(15):1831-4. doi:10.1182/blood-2015-04-637702. Epub 2015 Aug 14.   *Joint first authors

Griffiths RE, Kupzig S, Cogan N, Mankelow TJ, Betin VM, Trakarnsanga K, Massey EJ, Parsons SF, Anstee DJ, Lane JD. The ins and outs of human reticulocyte maturation: autophagy and the endosome/exosome pathway. Autophagy. 2012 Jul 1;8(7):1150-1.

Griffiths RE, Kupzig S, Cogan N, Mankelow TJ, Betin VM, Trakarnsanga K, Massey EJ, Lane JD, Parsons SF, Anstee DJ. Maturing reticulocytes internalize plasma membrane in glycophorin A-containing vesicles that fuse with autophagosomes before exocytosis. Blood. 2012 Jun 28;119(26):6296-306. 

Featured projects Duration
Ageing of the human haemopoietic stem cell niche
20172019