| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Bone marrow and peripheral blood contains endothelial progenitor cells (EPCs) that participate in neovascularization. EPCs have an important role on vasculogenesis and they are repoted to be enriched in CD34(+) cells derived from cord blood(CB). The hematopoietic stem cell is more enriched in CB of preterm infants than CB of term infants. However, little is known about EPCs from human CB of preterm infants. We classified preterm group as gestational age less than 37 weeks (n=27) and term groups as more than 37weeks (n=27). Mononuclear cells (MNCs) of CB were subjected to flow cytometric analysis to examine surface expression of CD34, CD133, VEcadherin, CD117, VEGFR2/KDR and VEGFR3. Though the percentage of CD34^+ and VEGFR3^+ cells was no significant differences in any groups, the percentage of KDR(+) cells in CD34^+ and CD133^+ were significantly enriched in preterm group (P<0.01). CD34^+VEGFR3^+cells, which thought to be presumptive lymphatic EPCs, were significantly higher in preter
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m group (P<0.05). To examine the existence of EPCs in CB, MNCs were cultured on fibronectin coated plates. The numbers of attaching (AT) cells, which are tought to be presumptive EPCs, are more enriched in preterm CB (P<0.05), which is consistent with phenotypic analysis.
Moreover, VEGF (307±366pg/mL versus 20.2±21.8pg/mL, P<0.001), SDF-1α (,693±355pg/mL versus 513±194pg/mL P<0.01) and SCF which mobilize EPC from BM are higher in preterm CB. Thus, higher concentration of EPC mobilizing cytokines may give an account for the reason why CB in preterm infants contain higher rate of EPC. Interestingly, we demonstrated that VEGF-C which is ligand of VEGFR-2 and VEGFR-3 is significantly higher in preterm CB than term CB(41.5±28.0pg/mL versus 26.5±5.8pg/mL, P=0.017). These results suggest that CD133^+ VEGFR3^+ cells derived from preterm CB have strong outgrowth activity through the VEGF-C/VEGFR-3 and VEGF-C/VEGFR-2 signaling. Our findings suggest that preterm umbilical CB is a precious source for isolating EPC and putative lymaphatic EPC. Therefore, CB of preterm infants is an attractive source for several therapies by transplantation using EPC. Less
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