Search

Melanocytes are pigment-producing cells generated from neural crest cells ( NCCs) that delaminate from the dorsal neural tube. The widely accepted premise that NCCs migrating along the dorsolateral pathway are the main source of melanocytes in the skin was recently challenged by the finding that Schwann cell precursors are the major cellular source of melanocytes in the skin. Still, in a wide variety of vertebrate embryos, melanocytes are exclusively derived from NCCs. In this study, we show that a NCC population that is not derived from Sox1 + dorsal neuroepithelial cells but are derived from Sox1 − cells differentiate into a significant population of melanocytes in the skin of mice. Later, these Sox1 − cells clearly segregate from cells that originated from Sox1 + dorsal neuroepithelial cell-derived NCCs. The possible derivation of Sox1 − cells from epidermal cells also strengthens their non-neuroepithelial origin. [ABSTRACT FROM AUTHOR]

Embryonic stem (ES) cells from many organisms have the capacity to generate in vitro a wide variety of cell types depending on their environment. Understanding precisely how such toti- or pluripotent cells may be driven towards a specific lineage represents a major challenge if our ambition of using ES cells to generate a ready supply of healthy cells for cell-based therapies for a range of diseases is to be realized. Recent advances have demonstrated that melanocytes and retinal pigmented epithelial (RPE) cells exhibiting the characteristics of their natural counterparts can be induced from undifferentiated ES cells grown on monolayers of specific stromal cell lines or by using a combination of Wnt3a, Endothelin-3 and SCF. The ability to induce pigment cells from ES cells promises to facilitate our understanding of the precise molecular mechanisms underlying this process and moreover enable us to distinguish the program of gene expression that underpins the choice made between generating a nerual crest-type melanocyte versus an RPE cell. Moreover, once the combination of signals required to induce a particular type of pigment cell are characterized, the way may be open for future cell-based therapy for various diseases caused by defective pigment cells. [ABSTRACT FROM AUTHOR]

Background: We previously reported the usefulness of the IFNαGal epitope as a target molecule for gene therapy against cancer. To induce cancer cell specific transcription of the IFNαGal epitope, an expression vector which synthesizes the IFNαGal epitope under the control of a promoter region of the human telomerase reverse transcriptase (hTERT), NK7, was constructed. Methods: NK7 was transfected into a human pancreatic carcinoma cell line, MIA cells, and telomerase-negative SUSM-1 cells served controls. Expression of the IFNαGal epitope was confirmed by flow cytometry using IB4 lectin. The susceptibility of transfected MIA cells to human natural antibodies, was examined using a complement-dependent cytotoxic cross-match test (CDC) and a flow cytometry using annexin V. Results: The IFNαGal epitope expression was detected only on the cell surfaces of NK7-transfected MIA cells, i.e., not on naive MIA cells or telomerase negative SUSM-1 cells. The CDC results indicated that MIA cells transfected with NK7 are susceptible to human natural antibody-mediated cell killing, and the differences, as compared to NK-7 transfected telomerase negative SUSM-1 cells or telomerase positive naïve MIA cells, were statistically significant. The flow cytometry using annexin V showed a higher number of the apoptotic cells in NK-7 transfected MIA cells than in naïve MIA cells. Conclusions: The results suggest that IFNαGal epitope-expression, under the control of the hTERT-promoter, may be useful in cancer specific gene therapy. [ABSTRACT FROM AUTHOR]