Biomaterials that mimic the characteristics of bone marrow can alter the development of blood cells, say researchers at the University of Illinois. The technique developed by the researchers could potentially be used to grow hematopoietic stem cells in the lab that could be used for the treatment of hematopoietic diseases such as lymphoma and leukemia.
Treatment of both leukemia and lymphoma involves the transplanting of hematopoietic stem cells into the bone marrow. Hematopoietic stem cells are precursors for all cells in the immune system, as well as blood cells. However, there are problems with the treatment. Hematopoietic stem cells must be obtained from donors, and there is a limited supply. Secondly, the technique has a relatively low success rate. What oncologists need are large numbers of hematopoietic stem cells.
Growing donor HSCs in the lab could potentially resolve the supply problem, although doing so is problematic. In vivo, HSCs grow in an extra-cellular matrix, which provides a number of signals that control how the cells behave. Replicating the extracellular matrix in the lab and creating an environment where HSCs grow rapidly without differentiating has proved incredibly difficult.
However, Brendan Harley, a professor of chemical and biomolecular engineering at the University of Illinois and postdoctoral researcher Ji Sun Choi have made significant progress. They looked at the signals provided by the extracellular matrix and attempted to replicate the ECM in the lab. The purpose of the study was to see how engineered systems could be developed that could not only grow donor HSCs in the lab, but also control the rate of proliferation and cell differentiation.
Harley and Choi took samples of HSCs from mice and used a novel ECM constructed from biomaterials which mimicked the conditions in the bone marrow. The team looked at two elements of the ECM which are known to interact with HSCs in vivo: Collagen and fibronectin.
Harley and Choi used different biomaterials and altered the concentrations of both collagen and fibronectin and were able to control the speed at which HCSs grew, as well as controlling differentiation of HSCs into blood cells. Exposing HSCs to collagen resulted in rapid growth of HSCs; however, doing so resulted in the cells differentiating into blood cells, which would not be of use for transplantation. Using fibronectin resulted in slower growth of HSCs, although the cells did not differentiate and remained as HSCs.
Harley explained that “With the right combination of stiffness in the matrix and the presence of fibronectin, we identified a class of biomaterials that show promise for being able to maintain and eventually expand these stem cells outside of the body.”
There are of course many factors that potentially affect the speed at which cells can be grown. Harley’s research team is now investigating a host of other ECM features that can be manipulated to increase the number of stem cells that can be grown to levels that would make it viable to artificially grow HSCs in the lab for use in the treatment of hematopoietic diseases.
The research paper has recently been published in the journal Science Advances.