March 10, 2000

Protein controls proliferation of hematopoietic stem cells

An MGH research team has identified a key protein that appears to control the development and proliferation of hematopoietic stem cells. These cells, which are found in the bone marrow and blood, are capable of developing into any kind of blood cell. The discovery of a molecular switch that makes this possible, a protein called p21, may solve a major limitation to the use of these stem cells — the fact that they occur naturally in very small numbers and rarely reproduce.

"Hematopoietic stem cells tend to be very rare and inactive," says David Scadden, MD, of the MGH Cancer Center and AIDS Research Center, senior author of the study appearing in the March 10 issue of Science. "Stem cell transplants — as well as gene therapies that may someday be developed using these cells — need a lot of cells to ensure they will engraft in a recipient's marrow. If we could induce stem cells to proliferate without differentiating into specific types of blood cells, we could get the number of stem cells we need from a single tube of blood instead of having to extract a large amount of bone marrow."

Scadden continues: "Perhaps even more exciting are recent reports that some hematopoietic stem cells have the potential to develop into cells of many different types in addition to blood cells. If we could identify and expand the population of those cells, the possibilities for treating conditions — from injuries to cancer — would be enormous."

The study, led by Tao Cheng, MD, of Scadden's lab, confirmed that p21 acts like a molecular brake, keeping inactive stem cells from proliferating. The next step in the research will investigate whether inactivating p21 in a specialized cellular environment could allow cells to proliferate at high levels. The study's other co-authors are Neil Rodrigues, MS; Hongmei Shen, PhD; and David Dombkowski, of the MGH AIDS Research Center; and Yong-guang Yang, MD, PhD, and Megan Sykes, MD, of the MGH Transplantation Biology Research Center.