Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
Research Abstract |
To establish the human early phase-Kaposi's sarcoma model, we worked on seeking, and the isolation of non-transformed, proliferating XIIIa-positive mesenchymal dermal dendrocytes(FXIIIa DD) from the skin. We performed such trial in mice as the first step because it is known to be easier to isolate certain kind of mesenchymal cells from them. We succeeded in isolation of a population from enzymatically separated epidermis, which proliferate vigorously to undergo passage in RPMI culture in vitro, dependending only on fetal cuff serum. Then we cloned this cell line by limiting dilution, and named CMDC-1. Based on the results of DNA microarray analysis, CMDC-1 was supposed to belong to different cell population from fibroblasts. It expressed mRNA for the receptors of GM-CSF and IL-4, but not for factor XIIIa. By flow cytometry, it revealed that CMDC-1 constitutively expressed CD80, while showed positivity for I-A in reponse to IFNg. In contrast, they did not express CD14, CD45, CD68, CD86 with or without IFNg. Immunohistochemistry did not show positivity either for CD11b, CD31, CD34, CD106 or MECA32. These data suggested that CMDC-1 is mesenchymal-origin, although it belongs to other population than endothelial cells, and that it may have antigen-presenting capacity. To the best of our knowledge, the existence of cell lines with such phenotypes have not been reported so far. There is the possibility that CMDC-1 may differentiate into FXIIIa DD if it also express recptors proteins for such cytokines as GM-CSF and IL-4. CMDC-1 may be in line as a member of novel differentiation pathway of dermal dedrocytes and or mesencymal populations in vivo as well as the strong candidate for the component of early Kaposi's sarcoma lesion. Further investigation will reveal the pathomechanism of early Kaposi's sarcoma with the enigmatic ontogenesis of mesenchymal cells.
|