Home » Newsroom » HSCI Science Update » HSCI Science Update: April 2009

HSCI Science Update: April 2009

April 1, 2009

  • Engineering stem cells to destroy deadly tumors

    Mesenchymal stem cells (MSCs) are multipotent stem cells that are of particular interest for use in stem cell therapies because among other reasons, they are easy to isolate and culture, easy to genetically engineer to express foreign genes, and have a modulatory effect that mitigates immune rejection of the cells. One area in which MSCs are being extensively studied is in the treatment of glioma brain tumors. Many of these tumors are particularly aggressive with a median patient survival time of only about a year. It has been shown previously that MSCs have a propensity to migrate toward glioma cells and can be engineered to exert cytotoxic effects on these cells. This is particularly useful because many types of gliomas are highly invasive cancers that are difficult to remove surgically. Studies to date, however, have lacked a thorough characterization of how the engineered MSCs are actually functioning. HSCI Affiliate Faculty Khalid Shah, Principal Faculty Ralph Weissleder, and colleagues recently reported how they engineered multiple MSCs, observed their fate in a live mouse with glioma, and demonstrated that these engineered MSCs have significant anti-tumor effects. This study showed not only a potentially exciting way that stem cell therapy may be able to treat treat a relatively intractable and aggressive cancer, but also demonstrated how the use of advanced optical imaging to understand cellular function in vivo is applicable to cell therapy in general and will be critical to gaining clinical approval.

    Sasportas, L.S., Kasmieh, R., Wakimoto, H., Hingtgen, S., van de Water, J.A., Mohapatra, G., Figueiredo, J.L., Martuza, R.L., Weissleder, R., Shah, K. (2009). Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci USA 106, 4822-7.

  • A master switch for vertebrate organ regeneration

    In adult vertebrates, hematopoietic stem cells (HSCs), the stem cells that form the cell types found in the blood, reside in the bone marrow. During embryogenesis, multiple sites in the developing embryo are capable of producing HSCs. Understanding how these sites function and determining the complex signals regulating HSC development in these sites is an active area of investigation with the goal of understanding more about our ability to modulate HSC maintenance as an adult. HSCI Principal Faculty Len Zon, George Daley, Trista North, Wolfram Goessling, and colleagues published a paper that contributes significantly to our understanding of this process. The group showed that two signaling pathways, Prostaglandin E2 (PGE2) and the Wnt signaling pathway, interact to exert significant effects on HSC development. Excitingly, the researchers further note that the interaction between PGE2 and Wnt appears to be conserved in other instances of organ regeneration and that they may have uncovered a master regulator of vertebrate organ regeneration.

    Goessling, W., North, T.E., Loewer, S., Lord, A.M., Lee, S., Stoick-Cooper, C.L., Weidinger, G., Puder, M., Daley, G.Q., Moon, R.T., Zon, L.I. (2009). Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 136, 1136-47.

  • Helping stem cells find their way home

    The study of cell homing, engraftment and retention - how stem cells reach their proper destination in the body, how they incorporate, and how they stay there - is a critical area of focus for stem cell researchers. For example, the success of bone marrow transplants used to treat many types of cancers depends on this ability and a better understanding of the process is critical for us to be able to optimize therapies and treatments. Hematopoietic stem and progenitor cells (HSPCs) maintain a dynamic course throughout life, traveling through the bloodstream to enter and exit bone marrow stem cell niches through the series of steps of homing, engraftment, and retention. HSCI Scientific Co-Director David Scadden, HSCI Affiliate Faculty Henry Kronenberg, and colleagues recently described that the guanine-nucleotide-binding protein stimulatory alpha subunit (Galpha(s)) is necessary for HSPC engraftment of bone marrow during fetal development. These results are particularly exciting because they highlight a potential therapeutic target that may be used to enhance the efficiency of stem cell transplants in the treatment of certain types of cancers.

    Adams GB, Alley IR, Chung UI, Chabner KT, Jeanson NT, Celso CL, Marsters ES, Chen M, Weinstein LS, Lin CP, Kronenberg HM, Scadden DT. Haematopoietic stem cells depend on Galpha(s)-mediated signalling to engraft bone marrow. (2009). Nature Mar 25. [Epub ahead of print]