A NEUTRALIZING ANTI-TGF-BETA-1 ANTIBODY PROMOTES PROLIFERATION OF CD34(-1(+) PERIPHERAL-BLOOD PROGENITORS AND INCREASES THE NUMBER OF TRANSDUCED PROGENITORS()THY)

The subset of blood cells that expresses both CD34 and Thy1 (CD90) cel l surface molecules is enriched in hematopoietic stem cell activity an d can be obtained from the peripheral blood of cancer patients after m obilization by chemotherapy and granulocyte colony-stimulating factor (G-CSF). Because transforming growth factor-beta 1 (TGF-beta 1) is a p otent inhibitor of hematopoietic progenitor proliferation and differen tiation, in this study we analyzed the impact of neutralizing TGF-beta 1 activity during culture and retroviral transduction of CD34(+)Thy1( +) cells. When purified CD34(+)Thy1(+) cells were cultured in the pres ence of a neutralizing antibody against TGF-beta 1, the percentage of cycling cells, proliferation, and absolute number of clonogenic progen itors were increased in comparison to the cultures performed without t he addition of antibody. Antibody-mediated neutralization of TGF-beta 1 during retroviral transduction performed by coculture of CD34(+)Thy1 (+) cells with a MFG-S-nlsLacZ retroviral vector-producing cell line d id not affect the percentage of transduced progenitors as assessed by direct X-Gal staining of colonies in clonogenic assays. However, due t o the better expansion of CD34(+)Thy1(+) cells in the presence of anti -TGF-beta 1, the absolute number of transduced progenitors recovered a t the end of the culture was increased.