Determining the Origins of Blood cell-Making Stem Cells

Nancy Speck, professor of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania, and her team have discovered a molecular marker for the immediate precursors of blood-making stem cells in the developing embryo. This discovery provides insights that may eventually help biotechnology companies make blood-making stem cells by means of tissue engineering.

Blood making stem cells are found in the bone marrow of adults, and these stem cells produce all the blood cells found in blood. A deeper understanding of these cells may allow scientists to someday manipulate or even make blood-making stem cells for therapy. Speck and her colleagues stated: “The ultimate goal for stem-cell therapies is to take precursor stem cells and push them down a particular lineage to replace diseased or dead cells in human adults or children . . . You have to understand how this happens in the embryo.”

Previous studies strongly suggested that blood-making stem cells originated from a small population of cells that line blood vessels (endothelial cells). However, it is unclear precisely which endothelial cells transition to blood stem cells during early development. During embryonic development, multiple waves of blood-cell development occur. The first wave gives the embryo a quick source of oxygen, and the final wave sets up the development of blood-making stem cells that ultimately reside in adult bone marrow. Laboratory techniques can produce the first wave of blood cell progenitors from embryonic or induced pluripotent stem cells. However, efforts to produce blood-making stem cells have failed. By understanding the developmental origins of blood-cell forming stem cells, scientists can potentially produce them in the lab from embryonic or induced pluripotent stem cells.

How much closer does this study bring hematologists and other scientists to making blood cell-making stem cell stem cells in the laboratory? Presently, scientists can make blood cells from endothelial cells, and they can monitor such cells in the embryo. Not all endothelial cells can produce blood-cell forming stem cells. To find those cells that can form blood-cell forming stem cells, Speck’s team used a special marker to follow their development. Progenitor cells in the first wave of embryo blood-cell development and the blood-cell forming stem cells of later waves of development are differentiated from distinct populations of blood-producing endothelial cells by the expression of a marker called “Lya6a.” This marker is expressed in those endothelial cells that eventually form blood-cell forming stem cells and is not expressed in those endothelial cells that make the first wave of blood cells.

Knowing more about the development of blood cell-making stem cells and its distinct markers can help tissue engineers make blood cell-making stem cells in the lab for stem-cell therapies. Some leukemia patients cannot find suitable donors bone marrow donors, and these studies might help clinicians potentially patient’s own cells to make blood-cell forming stem cells to replace their diseased stem cells. Eventually, such techniques can even be used to make blood cells depleted by chemotherapy or blood cancers. Such technologies might be applicable to other treatments as well.