New Insight That "Mega" Cells Control the Growth of Blood-Producing Cells

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Newswise Kansas City, Mo. - While megakaryocytes are best known for producing platelets that heal wounds, these mega cells found in bone marrow also play a critical role in regulating stem cells according to new research from the Stowers Institute for Medical Research. In fact, hematopoietic stem cells differentiate to generate megakaryocytes in bone marrow. The Stowers study is the first to show that hematopoietic stem cells (the parent cells) can be directly controlled by their own progeny (megakaryocytes).

The findings from the lab of Stowers Investigator Linheng Li, Ph.D., described in the Oct. 19 issue of the journal Nature Medicine, could cause researchers to rethink what they know about the workings of megakaryocytes and potentially lead to new treatments for patients recovering from chemotherapy or organ transplantation.

Our results suggest that megakaryocytes might be used clinically to facilitate adult stem cell regeneration and to expand cultured cells for adult stem cell transplants, says Meng Zhao, Ph.D., a postdoctoral fellow at Stowers and lead author on the study. Stowers researchers discovered that megakaryocytes directly regulate the function of murine hematopoietic stem cellsadult stem cells that form blood and immune cells and that constantly renew the bodys blood supply. These cells can also develop into all types of blood cells, including white blood cells, red blood cells, and platelets.

Because of their remarkable ability to renew themselves and differentiate into other cells, hematopoietic stems cells are the focus of intense research and have been used to treat many diseases and conditions. The transplantation of isolated human hematopoietic stem cells is used in the treatment of anemia, immune deficiencies and other diseases, including cancer.

Basic research has centered on identifying and characterizing hematopoietic stem cells, however, it is still not clear how hematopoietic stem cells actually work, and how they are regulated because of the complexity of the bone marrow microenvironment. Zhao and his colleagues discovered that as a terminally differentiated progeny, megakaryocytes regulate hematopoietic stem cells by performing two previously unknown functions.

Megakaryocytes can directly regulate the amount of hematopoietic stem cells by telling the cells when they need to keep in the quiescent stage, and when they need to start proliferating to meet increased demand. Maintaining that delicate balance is important, he adds. You dont want to have too many or too few hematopoietic stem cells.

These findings are supported by similar research from the laboratory of Paul S. Frenette, Ph.D., at the Albert Einstein College of Medicine, also reported in the Oct. 19 issue of Nature Medicine.

Employing the advanced technology of the Institutes Cytometry, Imaging and Histology centers, the researchers examined the relationship between megakaryocytes and hematopoietic stem cells in mouse bone marrow. In the course of their research, they found that the protein transforming growth factor B1 (TGF-B1), contained in megakaryocytes, signaled quiescence of hematopoietic stem cells. They also found that when under stress from chemotherapy, megakaryocytes signaled fibroblast growth factor 1 (FGF1), to stimulate the proliferation of hematopoietic stem cells.

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New Insight That "Mega" Cells Control the Growth of Blood-Producing Cells