Concise review: parthenote stem cells for regenerative medicine: genetic, epigenetic, and developmental features

Abstract

Embryonic stem cells (ESCs) have the potential to provide unlimited cells and tissues for regenerative medicine. ESCs derived from fertilized embryos, however, will most likely be rejected by a patient's immune system unless appropriately immunomatched. Pluripotent stem cells (PSCs) genetically identical to a patient can now be established by reprogramming of somatic cells. However, practical applications of PSCs for personalized therapies are projected to be unfeasible because of the enormous cost and time required to produce clinical-grade cells for each patient. ESCs derived from parthenogenetic embryos (pESCs) that are homozygous for human leukocyte antigens may serve as an attractive alternative for immunomatched therapies for a large population of patients. In this study, we describe the biology and genetic nature of mammalian parthenogenesis and review potential advantages and limitations of pESCs for cell-based therapies.

Keywords: Histocompatibility; Imprinting; Parthenogenesis; Pluripotent stem cells.

Figure 1.

Meiosis and zygosity outcomes during parthenogenesis. (A): Normal fertilization with sperm. During the prophase I of meiosis I, the two parental chromosomes (depicted as white and black), each containing sister chromatids, recombine and exchange regions through chromosomal crossover. Meiosis I is resolved by extrusion of one homologous parental chromosome into the first polar body. The remaining homologous chromosome enters into meiosis II but remains arrested at metaphase II until fertilized by sperm. Meiotic progression resumes after fertilization. Sister chromatids segregate, and one chromatid is eliminated in the second PB. The sperm provides the second homologous chromosome to the diploid zygote. (B): Heterozygous parthenogenesis without completion of meiosis. After artificial activation that blocks second PB extrusion, sister chromatids segregate during anaphase II; however, both chromatids are retained within the oocyte, forming a diploid parthenogenetic zygote. Because of earlier meiotic recombination and crossover with the other homologous parental chromosomes, the resulting diploid parthenote exhibits high levels of heterozygosity. (C): Homozygous parthenogenesis after completion of meiosis. Artificial activation methods may not interfere with completion of meiosis and segregation of the second PB. However, the initial haploid genome replicates during mitotic S-phase without undergoing subsequent cell division. Both sister chromatids are retained as a homologous pair resulting in a diploid but homozygous parthenote. (D): Haploid parthenogenesis after completion of meiosis. Parthenogenetic activation renders a haploid genome that is maintained throughout subsequent mitotic divisions. Abbreviations: MII, metaphase II; PB, polar body; PI, prophase I of meiosis I.