Format

Send to

Choose Destination
Stem Cells. 2014 Jul;32(7):1983-8. doi: 10.1002/stem.1726.

Brief report: Parthenogenetic embryonic stem cells are an effective cell source for therapeutic liver repopulation.

Author information

1
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, California, USA; Department of Surgery, Division of Transplantation, University of California San Francisco, San Francisco, California, USA.

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.

KEYWORDS:

Embryonic stem cells; Liver cell therapy; Liver regeneration; Liver repopulation; Parthenogenesis; Pluripotent stem cells

PMID:
24740448
PMCID:
PMC4376534
DOI:
10.1002/stem.1726
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center