Differentiation Potential of Histocompatible Parthenogenetic Embryonic Stem Cells

Abstract

Embryonic stem cells (ESCs) hold unique promise for the development of cell replacement therapies, but derivation of therapeutic products from ESCs is hampered by immunological barriers. Creation of HLA-typed ESC banks, or derivation of customized ESC lines by somatic cell nuclear transfer, have been envisioned for engineering histocompatible ESC-derived products. Proof of principle experiments in the mouse have demonstrated that autologous ESCs can be obtained via nuclear transfer and differentiated into transplantable tissues, yet nuclear transfer remains a technology with low efficiency. Parthenogenesis provides an additional means for deriving ESC lines. In parthenogenesis, artificial oocyte activation initiates development without sperm contribution and no viable offspring are produced in the absence of paternal gene expression. Development proceeds readily to the blastocyst stage, from which parthenogenetic ESC (pESC) lines can be derived with high efficiency. We have recently shown that when pESC lines are derived from hybrid mice, early recombination events produce heterozygosity at the major histocompatibility complex (MHC) loci in some of these lines, enabling the generation of histocompatible differentiated cells that can engraft immunocompetent MHC-matched mouse recipients. Here, we explore the differentiation potential of murine pESCs derived in our laboratory.