A collaborative study between Boston University School of Public Health and researchers at Boston Medical Center has used induced pluripotent stem cells to make unlimited numbers of human red blood cells and platelets in culture.
This finding could potentially reduce the need for blood donations to treat patients who require blood transfusions. Such research could also help researchers examine fresh and new therapeutic targets in order to treat blood diseases such a sickle-cell anemia.
The lead scientist on this project was George Murphy, assistant professor of medicine at Boston University School of Medicine and co-director of the Center for Regenerative Medicine at Boston University. Murphy’s main collaborator was David Sherr, professor of environmental health at Boston University School of Medicine and the Boston University School of Public Health.
Induced pluripotent stem cells or iPSCs are made from adult cells by applying genetic engineering technology to the adult cells that introduces genes into them. The introduction of four specific genes de-differentiates the adult cells into pluripotent stem cells that can, potentially, differentiate into any adult cell type. This makes iPSCs powerful tools for research and potential therapeutic agents for regenerative medicine.
In this study, Murphy and others used iPSCs from the CreM iPS Cell Bank and exposed them to a battery of different growth factors in order to push them to differentiate into different adult cell types. They were looking for the precise cocktail to differentiate iPSCs into red blood cells, since they wanted to further study red blood cell development in detail.
One group of compounds given to the set of iPSCs were molecules that activate “aryl hydrocarbon” receptors. Aryl hydrocarbon receptors (AHRs) play important roles in the expansion of hematopoietic stem cells, which make blood cells, since antagonism of AHRs promotes expansion of hematopoietic stem cells (see AE Boitano et al.,Science 10 September 2010: Vol. 329 no. 5997 pp. 1345-1348). In this case, however, Murphy and his colleagues observed a dramatic increase in the production of functional red blood cells and platelets in a short period of time. THis suggests that the ARH is important for normal blood cell development.
“This finding has enabled us to overcome a major hurdle in terms of being able to produce enough of these cells to have a potential therapeutic impact both in the lab and, down the line, in patients,” said Murphy. “Additionally, our work suggests that AHR has a very important biological function in how blood cells form in the body.”
“Patient-specific red blood cells and platelets derived from iPSC cells, which would solve problems related to immunogenicity and contamination, could potentially be used therapeutically and decrease the anticipated shortage and the need for blood donation,” added Murphy.
iPS-derived cells have tremendous potential as model systems in which scientists can test and develop new treatments for disease, given that such diseases can be constructed in the laboratory. These iPSC-derived red blood cells could be used by malaria researchers, and IPSC-derived platelets could be used to explore cardiovascular disease and treatments for blood clotting disorders.
Because my mother died from myelodysplasia, this finding has some personal interest to me. Mom had a difficult blood type to match, since she had the Bombay blood type (H). Finding blood for her was a major tour de force, and as she received blood that was less and less well matched to her body, she suffered the ravages of poorly matched blood. A treatment of red blood cells made from IPSCs derived from her own cells might have extended her life and even improved her quality of life in her later years.
I look forward to this research eventually culminating in clinical trials.