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HSCI Science Update: June 2009

June 30, 2009

  • The skinny on fat and blood

    Adult bone marrow contains fat cells or adipocytes and the number of fat cells is inversely proportional to the marrow's blood cell making activity (hematopoiesis). After bone marrow irradiation or chemotherapy, the number of adipocytes in the bone marrow increases, as it also does in cases of bone marrow failure, or aplasia. In a recently published paper in Nature, HSCI investigators were interested in exploring the relationship between the adipocytes and hematopoiesis, whether the adipocytes filled up inactive marrow or if they actually had a regulatory function. In order to address this question, HSCI Executive Committee member George Daley (CHB) and colleagues measured adipocyte levels in the hematopoietically active and inactive regions of a mouse, as well as in animals unable to form adipocytes. The researchers found that the adipocytes appeared to negatively regulate hematopoiesis. This finding is useful therapeutically because it suggests that preventing adipocytes in the marrow could facilitate hematopoiesis after a bone marrow transplant.

    Naveiras, O., Nardi, V., Wenzel, P.L., Hauschka, P.V., Fahey, F., Daley, G.Q.(2009). Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature. Jun 10. [Epub ahead of print]

  • Hematopoietic stem cells - a heartbeat away

    In a paper just released in the journal Cell, HSCI Principal Faculty members Trista North (BIDMC), Wolfram Goessling (BWH), and colleagues in the lab of HSCI Executive Committee chair Len Zon (CHB) report on factors that regulate hematopoietic stem cell (HSC) development.

    While postdocs in the Zon lab, they looked at mutant zebrafish embryos that lacked a heartbeat and blood flow. The HSCs in these "silent heart" mutants did not develop normally, suggesting that heartbeat and blood flow were required for HSCs to form. Co-author Goessling notes "this study reveals the biological reason for the heartbeat to start so early in embryonic development - before it is necessary for oxygen delivery - is because it acts as a trigger to develop the next wave of "adult-type" blood stem cells."

    The researchers also identified additional factors involved in regulating HSC development. Nitric oxide has been previously identified as a regulator of many physiological processes including blood vessel formation. In this work, the scientists discovered a new role for nitric oxide in HSC development. As co-author North describes, "Nitric oxide (NO) is the perfect mediator for this type of process - it is produced by shear stress and can alter both endothelial cell interactions and movement.   In this manner local elevations in NO levels would permit the initial budding of stem cells from the blood vessel wall."

    It is particularly exciting to discover new, additional regulators of the process because the greater the number of factors that can be identified, the better our understanding of the complex signaling network that regulates HSC formation. The better our understanding of early formation, the better our understanding of ongoing maintenance, because many of the same factors that control HSC development also regulate their maintenance in the adult and could be useful therapeutic targets for treating bone marrow diseases. Senior author Len Zon notes, "Our study demonstrates that blood flow is a critical regulator of blood stem cell production in an embryo.   By providing the relevant blood flow signaling factor, nitric oxide, it may be possible to help embryonic stem cells to become blood stem cells.   This would potentially provide patients with an alternative source of blood stem cells, which is helpful when an immune system match is not available. "

    North, T.E., Goessling, W., Peeters, M., Li, P., Ceol, C., Lord, A.M., Weber, G.J., Harris, J., Cutting, C.C., Huang, P., Dzierzak, E., Zon, L.I. (2009). Hematopoietic stem cell development is dependent on blood flow. Cell. 137, 736-48.

  • All eyes on polymer scaffolds for retinal repair

    Loss of vision due to retinal degeneration affects millions of people. A recent study in mouse showed the promise of a retinal tissue engineering approach using a biodegradable polymer scaffold on which mouse retinal progenitor cells are allowed to differentiate. To explore the feasibility of such an approach for retinal tissue engineering restorative therapy, HSCI Affiliated Faculty member Michael Young (Schepens Eye Research Institute) and colleagues made and studied a micro-fabricated polymer to which they were able to adhere mouse retinal progenitor cells. In their recently published paper in Biomaterials, they report that these mouse retinal progenitor cells differentiated into more mature cell types and were able to survive long term when transplanted. These results are encouraging in that they suggest that this may be developed further as a practical strategy for retinal tissue engineering.

    Redenti, S., Neeley, W.L., Rompani, S., Saigal, S., Yang, J., Klassen, H., Langer, R., Young, M.J. (2009). Engineering retinal progenitor cell and scrollable poly(glycerol-sebacate) composites for expansion and subretinal transplantation. Biomaterials. 30, 3405-14. Epub 2009 Apr 9.