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Trans-inner Cell Mass Injection of Embryonic Stem Cells Leads to Higher Chimerism Rates
Published on: May 29, 2018
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Interspecies Chimerism with Mammalian Pluripotent Stem Cells
Jun Wu1, Aida Platero-Luengo1, Masahiro Sakurai1
1Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Cell
|January 28, 2017
Summary
Researchers explored human pluripotent stem cells (hPSCs) in pig and cattle embryos. Intermediate hPSCs showed significant contribution to pig embryo development, advancing xenogeneic organ generation potential.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Xenotransplantation Research
Background:
- Interspecies blastocyst complementation facilitates organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives.
- CRISPR-Cas9 technology enables versatile blastocyst complementation platforms for studying embryogenesis and disease models.
- The potential for human organ generation in animals necessitates understanding human PSC (hPSC) contribution in diverse mammalian species.
Purpose of the Study:
- To establish a versatile blastocyst complementation platform using CRISPR-Cas9 for gene-edited organogenesis-disabled mice.
- To evaluate the chimeric competency of various hPSC types in ungulate species (pigs and cattle).
- To determine the potential for hPSC contribution to chimera formation in non-rodent species for future organ generation.
Main Methods:
- Development of a CRISPR-Cas9-mediated zygote genome editing platform for blastocyst complementation.
- Systematic evaluation of different hPSC types for engraftment and contribution in pig and cattle pre- and post-implantation embryos.
- Assessment of differentiated progeny generation from engrafted hPSCs in post-implantation pig embryos.
Main Results:
- Rat PSC derivatives were enriched in multiple tissues of gene-edited, organogenesis-disabled mice.
- Naïve hPSCs demonstrated robust engraftment in both pig and cattle pre-implantation blastocysts.
- Intermediate hPSCs exhibited a higher degree of chimerism and generated differentiated progeny in post-implantation pig embryos, unlike naïve hPSCs which showed limited contribution.
Conclusions:
- The study successfully established a versatile blastocyst complementation platform for interspecies studies.
- Intermediate hPSCs show promise for contributing to chimera formation in ungulate species, specifically pigs.
- These findings advance the potential for human organ generation in animals with physiology closer to humans.
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