Application of nuclear transferred embryonic stem cells for reconstitution of hematopoiesis

点击翻译按钮获取中文摘要

The establishment of a number of human embryonic stem (ES) cell lines has spurred research into the potential applications of such cells. The use of ES cell-derived cell populations for cell therapy appears to be one of the more promising clinical applications. However, there are a few reasons to limit clinical uses of the cells derived from ES cells. One is in the case of a mismatch of major histo-compatibility (MHC) antigen between the ES cells and the recipient's cells. This limitation may be overcome in several ways: an induction of tolerance in the recipient using ES cell-derived antigen-presenting cells; production of many ES cell lines to cover many types of MHC; production of cloned ES cell lines that possess nuclei derived from the recipient, i.e. so called "therapeutic cloning".The establishment of nuclear transferred ES (ntES) cell line is possible with mouse oocytes and nuclei. On the other hand, although the establishment of human ntES cell line has not been succeeded yet, … More it is highly likely that the technology to establish human ntES cell line will be developed in the future. Prior to the use of human ntES cell lines in the clinic, many basic researches should be performed using mouse and/or primate ntES cell lines.Since many groups have already reported that hematopoietic cells can be derived from human ES cells, hematopoietic cells may be also derived from human ntES cells. Then, we have tested whether hematopoietic cells can be derived from mouse ntES cells. First, we have analyzed the characteristics of several mouse ntES cell lines. All mouse ntES cell lines tested have demonstrated that they have the characteristics quite similar to ordinary ES cell lines, e.g., in morphology, cell surface phenotype, and gene expression pattern. Next, we have tested whether mouse ntES cells could produce hematopoietic cells following the induction of those cells into hematopoietic cells. As the results, all mouse ntES cell lines tested could produce hematopoietic cells robustly.We are currently studying whether hematopoietic stem cells are included in the hematopoietic cell population produced from mouse ntES cells. In addition, we will test the potential of those hematopoietic stem cells whether they can reconstitute hematopoietic cells in vivo by transplantation assay. Less