Anatomical Compartments Modify the Response of Human Hematopoietic Cells to a Mitogenic Signal

¹ University of Washington, Seattle, Washington
² Fred Hutchinson Cancer Research Center, Seattle, Washington

^* To whom correspondence should be addressed. E-mail: tblau{at}u.washington.edu.

	Abstract

Methods for specifically regulating transplanted cells have many applications in gene and cell therapy. We examined the response of human cord blood CD34⁺ cells, to a specific mitotic signal, in vivo. Using a conditional signaling molecule (F36VMpl) that is specifically activated by an artificial ligand called a chemical inducer of dimerization (CID), human hematopoietic cells transplanted into immune deficient mice were induced to proliferate. Only differentiating erythroid precursors and multipotential and erythroid progenitors (CFUmix and BFUe) responded, however the nature of the response differed markedly between bone marrow and spleen. In the marrow, F36VMpl induced a 12-17 fold expansion of differentiated erythroid precursors, and a loss of CFUmix and BFUe. In the spleen, F36VMpl induced a marked rise in BFUe and CFUmix and, relative to marrow, a much less prominent rise in more mature red cells. Clonal analysis was most consistent with the interpretation that the spleen and bone marrow differentially regulate the response of human progenitors to a mitotic signal, possibly influencing progenitor expansion versus differentiation. These findings establish CIDs as in vivo growth factors for human hematopoietic cells.