Generation of Rat Pancreas in Mouse by Interspecific Blastocyst Injection of Pluripotent Stem Cells

被引：445

作者：

Kobayashi, Toshihiro ^{[1
,2
]}

Yamaguchi, Tomoyuki ^{[1
,2
]}

Hamanaka, Sanae ^{[1
,2
]}

Kato-Itoh, Megumi ^{[2
,3
]}

Yamazaki, Yuji ^{[1
,2
]}

Ibata, Makoto ^{[2
]}

Sato, Hideyuki ^{[1
,2
]}

Lee, Youn-Su ^{[1
,2
]}

Usui, Jo-ichi ^{[1
]}

Knisely, A. S. ^{[5
]}

Hirabayashi, Masumi ^{[3
,4
]}

Nakauchi, Hiromitsu ^{[1
,2
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Ctr Stem Cell Biol & Regenerat Med, Div Stem Cell Therapy,Minato Ku, Tokyo 1088639, Japan

[2] Japan Sci & Technol Agcy, ERATO, Nakauchi Stem Cell & Organ Regenerat Project, Minato Ku, Tokyo 1088639, Japan

[3] Natl Inst Nat Sci, Natl Inst Physiol Sci, Ctr Genet Anal Behav, Okazaki, Aichi 4448585, Japan

[4] Grad Univ Adv Studies, Sch Life Sci, Okazaki, Aichi 4448585, Japan

[5] Kings Coll Hosp London, Inst Liver Studies, London SE5 9RS, England

来源：

CELL | 2010年 / 142卷 / 05期

关键词：

DIFFERENTIATION; MICE; TRANSPLANTATION; CULTURE; PIGS;

D O I：

10.1016/j.cell.2010.07.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：787 / 799

页数：13

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