Hematopoietic potential of histocompatible embryonic stem cell lines

Sloan-Kettering Inst Can Research, New York NY

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Abstract

PROJECT SUMMARY (See instructions): The goal of this research is to create histocompatible patient specific hematopoietic stem cells, which in addition to their potential therapeutic value, will provide novel tools for in-depth study of reprogramming and differentiation. The Specific Aims of this proposal are: Specific Aims 1: Generation of histocompatible mmctES cells using microcell mediated chromosome transfer (mmct) in mouse. Specific Aim 2: Testing of hematopoietic potential in mmctES cells by in vitro and in vivo methods. The limited availability of human oocytes required for both nuclear transferred (nt) ES and parthenogenetic (p) ES cell techniques poses a significant obstacle to generating customized embryonic stem cells. Therefore, alternative methods to generate similar types of cells are needed. Generation of ES cells by oocyte free methods already has been demonstrated by fusion of somatic cells (sc) and embryonic stem (es) cells to reprogram the somatic cells. However, removal of the genetic material from the resultant tetraploid sc-es hybrid ES cells to make diploid ES cells has not been achieved. As an alternative approach, I propose microcell-mediated transfer to ES cells of mouse sc-chromosome 17 and human sc-chromosome 6, which contain the major histocompatibility complex (MHC). The resultant duplicated mouse es-chromosome 17 and human sc-chromosome 6 will then be removed to make diploid mmctES cells in mouse