The Stem Cell Podcast

Ep. 86: “Human-Pig Chimera” Featuring Dr. Jun Wu

Feb 28, 2017
Dr. Jun Wu, a developmental biologist at the Salk Institute who studies interspecies chimerism, joins to discuss human–pig chimera research. He explains what chimeras are and why pigs are chosen. He covers CRISPR-created host niches, differences between naive and primed stem cells, ethical safeguards, and next steps to boost human cell contribution in pigs.
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ANECDOTE

Long Lived Rat Mouse Chimeras With Functional Donor Cells

  • Rat→mouse chimeras produced viable adults and even two-year-old chimeric animals with functional donor-derived tissues.
  • Wu described rat cells contributing up to ~10% in heart of an older chimera while liver contribution remained extremely low.
ADVICE

Use Zygote Gene Editing To Create Developmental Niches

  • Use embryo zygote gene editing to create niche vacancies and enrich donor cell contribution rather than waiting years to make mutant host lines via ESCs.
  • Jun Wu used CRISPR-Cas9 in zygotes to disable organ development and complemented with donor PSCs to enrich organs like pancreas.
INSIGHT

Evolutionary Distance Creates A Major Chimerism Barrier

  • Evolutionary distance strongly limits donor cell contribution: rat→mouse chimerism reached up to ~20–25%, while human→pig contribution was roughly 1 in 100,000 cells at 3–4 weeks.
  • Low human contribution suggests technical and biological species barriers that must be lowered for organ generation in pigs.
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