Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells.
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.
Kobayashi
Toshihiro
T
Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Yamaguchi
Tomoyuki
T
Hamanaka
Sanae
S
Kato-Itoh
Megumi
M
Yamazaki
Yuji
Y
Ibata
Makoto
M
Sato
Hideyuki
H
Lee
Youn-Su
YS
Usui
Jo-Ichi
J
Knisely
A S
AS
Hirabayashi
Masumi
M
Nakauchi
Hiromitsu
H
D000818:Animals; D001755:Blastocyst; D002678:Chimera / Q000196:embryology*; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000628:therapy; D047108:Embryonic Development; D055879:Gene Knock-In Techniques; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D038081:Organogenesis; D010179:Pancreas / Q000166:cytology* / Q000196:embryology*; D039904:Pluripotent Stem Cells; D051381:Rats; D017208:Rats, Wistar; D015534:Trans-Activators / Q000235:genetics
D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein