Generation of Rat Pancreas in Mouse by Interspecific Blastocyst Injection of Pluripotent Stem Cells
Author(s) -
Toshihiro Kobayashi,
Tomoyuki Yamaguchi,
Sanae Hamanaka,
Megumi KatoItoh,
Y. Yamazaki,
Makoto Ibata,
Hideyuki Sato,
Youn-Su Lee,
Joichi Usui,
A. S. Knisely,
Masumi Hirabayashi,
Hiromitsu Nakauchi
Publication year - 2010
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2010.07.039
Subject(s) - biology , blastocyst , induced pluripotent stem cell , stem cell , microbiology and biotechnology , interspecific competition , pancreas , embryo , embryoid body , induced stem cells , embryonic stem cell , genetics , botany , embryogenesis , endocrinology , gene
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.
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