Understanding the biological signals and their temporal magnitude involved in the division, maturation and migration of haematopoietic stem cells (HSCs) and their differentiated progeny would allow for a controlled continuous production of mature blood cells. By careful selection of a 3-dimensional micro-environment it is possible to mimic the niche within bone marrow in which haematopoiesis occurs. Further, by design and control of the flow profile within this microenvironment, it is possible to fine tune the rate of departure of the differentiating cells into a separate microenvironment suitable for further maturation, so creating the conditions for the generation of mature blood cells which could be a continuous process. This research will determine the requirements for the control of the fluidic behaviour within bioreactors for the generation of HSC. Complex, composite systems that allow for the temporal and spatial separation of microenvironments allowing for not only variation in the fluid flow and oxygen tension, but a change in the chemical nature of the culture conditions, will provide the opportunity for delivery of controlling factors. The principle is based on the ability to provide nutritional exchange with an overall zero, or very small, net mass transport. Mechanical design will allow us to match the rate of HSC division, providing the opportunity to derive the daughter cells into the correct environment for red blood cell development over an appropriate time frame. Differentiation of HSCs into different blood cell types occurs within different bone marrow niches and so mimicry of the erythrocyte niche is likely to result in maximisation of the rate of red blood cell development.
Field of science
- /medical and health sciences/medical biotechnology/cells technologies/stem cells
- /social sciences/sociology/social problems/migration
- /engineering and technology/environmental biotechnology/bioremediation/bioreactor
- /social sciences/social and economic geography/transport
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