[show abstract][hide abstract] ABSTRACT: Fibroblast growth factor (FGF) and FGF receptor (FGFR) are expressed in various cells including endothelial progenitor cells and hematopoietic cells. The interaction between FGF and FGFR is associated with the proliferation, migration, and survival of these cells. In this report, we examined the effects of FGFR2 signaling on hematopoiesis in immature hematopoietic cells, using mutant mice in which a constitutively active form of FGFR2 mutant was caused to be overexpressed by the Tie2 promoter (FGFR2 Tg mice). Under normal conditions, hematopoiesis of FGFR2 Tg mice and wild type (Wt) mice do not differ significantly, except for the weight and cell numbers of the thymus. However, the c-kit(+)Sca-1(+)lineage⁻ bone marrow cells (BMCs) of FGFR2 Tg mice facilitate the formation of colony-forming units of culture. When these BMCs were transplanted into the recipient bone marrow (intra-bone marrow-bone marrow transplantation), there was better reconstitution of donor hematopoietic cells. In the in vitro experiment, the c-kit(+)Sca-1(+)lineage⁻ BMCs from FGFR2 Tg mice showed fewer apoptotic cells than those from Wt mice. These results suggest that the antiapoptotic effect of FGFR2 signaling facilitates the hematopoiesis of FGFR2 Tg mice.
Stem cells and development 03/2010; 19(11):1679-86. · 4.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: (NZW x BXSB)F1 mice (W/BF1 mice) have been reported to develop autoimmune diseases with aging. We have also reported that the number of dendritic cells (DCs) increases in the various organs, and that the B-cell response to LPS or interleukin-4 plus anti-mu increase with aging in W/BF1 mice. In the present experiment, we show that many DCs exist not only in the T-cell area but also in the B-cell area and the sinus in the spleen of aged W/BF1 mice, and that the coculturing of DCs from aged W/BF1 mice and B cells from disease-free young W/BF1 mice produces much more IgG and IgM than normal mice. These results suggest that an abnormal distribution of DCs and the interaction of DCs and B cells induce the hyperproduction of immunoglobulin in aged W/BF1 mice.
[show abstract][hide abstract] ABSTRACT: The collection of bone marrow cells (BMCs) using a perfusion method has been advantageous not only because of the low contamination of BMCs with T cells from the peripheral blood but also the enrichment of stromal cells, which support hemopoiesis. Before the application of this new method to humans, its safety needed to be confirmed using cynomolgus monkeys. We therefore performed the perfusion method on more than 100 cynomolgus monkeys using the long bones (such as the humerus and femur) and also the iliac bones (for human application); in the more than 150 trials to date, there have been no accidental deaths. Furthermore, the technical safety of a new method for the intra-bone marrow (IBM) injection of BMCs (termed IBM-bone marrow transplantation) has also been confirmed using 30 monkeys. Disclosure of potential conflicts of interest is found at the end of this article.