Cell
Volume 142, Issue 5, 3 September 2010, Pages 787-799
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Article
Generation of Rat Pancreas in Mouse by Interspecific Blastocyst Injection of Pluripotent Stem Cells

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Summary

The complexity of organogenesis hinders in vitro generation of organs derived from a patient's pluripotent stem cells (PSCs), an ultimate goal of regenerative medicine. Mouse wild-type PSCs injected into Pdx1−/− (pancreatogenesis-disabled) mouse blastocysts developmentally compensated vacancy of the pancreatic “developmental niche,” generating almost entirely PSC-derived pancreas. To examine the potential for xenogenic approaches in blastocyst complementation, we injected mouse or rat PSCs into rat or mouse blastocysts, respectively, generating interspecific chimeras and thus confirming that PSCs can contribute to xenogenic development between mouse and rat. The development of these mouse/rat chimeras was primarily influenced by host blastocyst and/or foster mother, evident by body size and species-specific organogenesis. We further injected rat wild-type PSCs into Pdx1−/− mouse blastocysts, generating normally functioning rat pancreas in Pdx1−/− mice. These data constitute proof of principle for interspecific blastocyst complementation and for generation in vivo of organs derived from donor PSCs using a xenogenic environment.

Highlights

Pdx1−/− mice provide developmental niche for blastocyst complementation approach ► Mouse pluripotent stem cell (PSC)-derived pancreas is generated in Pdx1−/− mice ► Generation of interspecific chimeras between mouse and rat using PSCs of each ► Generation of rat pancreas in mouse via interspecific blastocyst complementation

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Present address: Department of Nephrology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan