Engineering haematopoietic microniches: the hematon project

Blood is produced in bone marrow. Within bone marrow small clumps of cells have been found, called hematons, which are able to produce all the types of cells found in blood. It is not known how a hematon is able to do this, and the aim of the project is to find out how it does. To do this, we will try to make hematons outside the body. Because we do it outside the body, we can exactly control the composition of the hematon, in terms of the different cell types it consists of as well as the material that is found outside the cells. In addition, we can also precisely control the position of the different cells by guiding them to specific positions within a reconstructed hematon.

In this project the hematon, the smallest multicellular unit capable of self-reproduction and the formation of all cell types found in blood, will be recreated in vitro. In order to do this, microfabrication and micromanipulation techniques will be combined with cell immobilisation techniques to create 3-dimensional cell aggregates with different compositions and architectures. Stem cells will be introduced into the cell aggregates, and the effect of the microenvironment on stem cell renewal, expansion and differentiation will be studied. In addition, laser tweezer technology will be used to move stem cell progeny between different microenvironment, enabling one to study the commitment of the stem cell progeny to its fate. Multiparameter flow cytometry, confocal microscopy and real time PCR will be used to isolate and characterise the primary stem cells and their progeny to be used in the project.