Dendritic cells support hematopoiesis of bone marrow cells

Background. We previously observed that vaccination of normal mice with bon e marrow (BM) -derived dendritic cells (DCs) could increase the number of p eripheral white blood cells (WBCs) and platelets. In the present study, we investigated the potential of DCs to support the hematopoiesis of BM cells in vitro and in vivo. Methods. In the absence of exogenous cytokines, the expansion of CD34(+) st em cells was observed when cultured with DC-derived supernatant or contact cocultured with DC. After culture in supernatant of DCs or contact cocultur e with DCs for 3 days, CD34(+) progenitor cells were cultured in the semiso lid media to test their ability to generate the clonogeneic cells. Then, BM cells combined with DCs or not were transferred into lethally irradiated s yngeneic recipients to determine the effects of DCs on hematopoietic recove ry. Results. After culture in the supernatant of DCs, especially in the superna tant of OVA-DCs (OVA-stimulated DQ, the proliferation of CD34(+) stem cells and generation of clonogeneic cells were augmented in correspondence with the concentration of DCs. After contact coculture with DCs, the proliferati on of CD34(+) stem cells and generation of clonogeneic cells were more sign ificant than that in noncontact cultures. Moreover, when cultured with DCs or supernatant of DCs, CD34(+) progenitor cells were preferentially differe ntiated to megakaryocytes. After coculture with OVA-DCs, markedly greater g eneration of colony forming units-granulocyte/macrophages (CFU-GM): colony forming units-megakaryocytes (CFU-MR) was found than that in coculture with unstimulated DCs. Pretreatment of DC with antibodies to thrombopoietin (TP O), interleukin (IL) -6, IL-12, or anti-mouse intercellular adhesion molecu le-1 (ICAM-1) could inhibit the ability of DCs to support the generation of CFU-GM, CFU-MK. After transplant with BM cells and DCs, the number of peri pheral platelets of the recipients increased significantly and, to a lesser extent, peripheral WBC counts increased. The survival periods were signifi cantly prolonged when the lethally irradiated mice were transplanted with B M cells combined with DCs or OVA-DCs. High levels of TPO, IL-6, and IL-12 c ould be detectable in the supernatant of DCs, and TPO expression by DCs was further confirmed by reverse transcription-polymerase chain reaction analy sis and intracellular staining with anti-TPO antibody. Conclusions. We first demonstrated that DCs, especially antigen-stimulated DCs, can promote the expansion of hematopoietic progenitors and support hem atopoiesis, preferentially support megakaryopoiesis of BM cells, by express ing soluble factors, including TPO, IL-6, IL-12, and by direct cell-to-cell interaction with stem cells in vitro and in vivo.