Brief Report: Parthenogenetic Embryonic Stem Cells are an Effective Cell Source for Therapeutic Liver Repopulation

Abstract

Parthenogenesis is the development of an oocyte without fertilization. Mammalian parthenogenetic (PG) embryos are not viable, but can develop into blastocysts from which embryonic stem cells (ESCs) have been derived in mouse and human. PG ESCs are frequently homozygous for alleles encoding major histocompatibility complex (MHC) molecules. MHC homozygosity permits much more efficient immune matching than MHC heterozygosity found in conventional ESCs, making PG ESCs a promising cell source for cell therapies requiring no or little immune suppression. However, findings of restricted differentiation and proliferation of PG cells in developmental chimeras have cast doubt on the potential of PG ESC derivatives for organ regeneration. To address this uncertainty, we determined whether PG ESC derivatives are effective in rescuing mice with lethal liver failure due to deficiency of fumarylacetoacetate hydrolase (Fah). In developmental chimeras generated by injecting wild-type PG ESCs into Fah-deficient blastocysts, PG ESCs differentiated into hepatocytes that could repopulate the liver, provide normal liver function, and facilitate long-term survival of adult mice. Moreover, after transplantation into adult Fah-deficient mice, PG ESC-derived hepatocytes efficiently engrafted and proliferated, leading to high-level liver repopulation. Our results show that—despite the absence of a paternal genome—PG ESCs can form therapeutically effective hepatocytes.

Mouse Parthenogenetic Embryonic Stem Cells with Biparental-Like Expression of Imprinted Genes Generate Cortical-Like Neurons That Integrate into the Injured Adult Cerebral Cortex

“…Mouse and human Pg‐ESCs can be differentiated in vitro and in vivo into derivatives of all germ lineages , including neural lineages . Pg‐ESCs have therefore emerged as a potent source of histocompatible cells for liver , heart , hematopoietic tissue , tendon , and the substantia nigra . Finally, Pg‐ESCs are a more accessible source with less ethical concerns than Bp blastocysts developed from sperm fertilized‐eggs.…”

Non‐coding RNAs: emerging regulatory factors in the derivation and differentiation of mammalian parthenogenetic embryonic stem cells

“…Besides, in developmental chimeras, PESCs differentiated into hepatocytes that could repair the injured liver and achieve normal liver function in mice. PESC-derived hepatocytes efficiently engrafted and proliferated, and lead to liver repopulation, indicating that PESCs can form therapeutically effective hepatocytes (Espejel et al, 2014).…”

“…To date, PESCs have been successfully derived from several mammalian species including human, mouse, bovine, porcine, and rabbit (Bevacqua et al, 2011;De Sousa et al, 2016;Intawicha et al, 2016;Kim et al, 2016;Zhong et al, 2016). (Onodera et al, 2010;Espejel et al, 2014;Schmitt et al, 2015;Sagi et al, 2016). They have been widely used in regenerative medicine due to their capacity to differentiate into various cell types both in vitro and in vivo, and are also the most ideal material in being to study the distinct roles of paternal and maternal genomes during development of multiple systems/organs/tissues, including and neural system, brain, lung, liver, and heart, etc.…”

“…They have been widely used in regenerative medicine due to their capacity to differentiate into various cell types both in vitro and in vivo, and are also the most ideal material in being to study the distinct roles of paternal and maternal genomes during development of multiple systems/organs/tissues, including and neural system, brain, lung, liver, and heart, etc. (Onodera et al, 2010;Espejel et al, 2014;Schmitt et al, 2015;Sagi et al, 2016). Mammalian PESCs are an important way to produce patient-specific stem cell lines or terminal differentiated cells, which are histocompatible cells, for cellbased therapy.…”

Directing the Differentiation of Parthenogenetic Stem Cells into Tenocytes for Tissue-Engineered Tendon Regeneration

“…These common HLA haplotype‐matched pSCs may reduce the risk of immune rejection after transplantation of their differentiated derivatives, thus offering significant advantages for application to cell‐based therapies compared with ESCs . pSCs can develop into retinal pigment epithelium‐like cells , muscle‐like and bone‐like cells , neuronal cells , , and hepatocytes . Moreover, cardiomyocytes derived from pSCs have been reported to facilitate engineering of myocardium and have been shown to enhance regional myocardial function after myocardial damage.…”