title: Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs.
abstract: In the field of regenerative medicine, one of the ultimate goals is to generate functioning organs from pluripotent cells, such as ES cells or induced pluripotent stem cells (PSCs). We have recently generated functional pancreas and kidney from PSCs in pancreatogenesis- or nephrogenesis-disabled mice, providing proof of principle for organogenesis from PSCs in an embryo unable to form a specific organ. Key when applying the principles of in vivo generation to human organs is compensation for an empty developmental niche in large nonrodent mammals. Here, we show that the blastocyst complementation system can be applied in the pig using somatic cell cloning technology. Transgenic approaches permitted generation of porcine somatic cell cloned embryos with an apancreatic phenotype. Complementation of these embryos with allogenic blastomeres then created functioning pancreata in the vacant niches. These results clearly indicate that a missing organ can be generated from exogenous cells when functionally normal pluripotent cells chimerize a cloned dysorganogenetic embryo. The feasibility of blastocyst complementation using cloned porcine embryos allows experimentation toward the in vivo generation of functional organs from xenogenic PSCs in large animals.
authors: Japan Science and Technology Agency, Exploratory Research for Advanced Technology, Nakauchi Stem Cell and Organ Regeneration Project, Chiyoda-ku 102-0075, Japan.
authors: Hitomi
authors: H
authors: Matsunari
authors: Hiroshi
authors: H
authors: Nagashima
authors: Masahito
authors: M
authors: Watanabe
authors: Kazuhiro
authors: K
authors: Umeyama
authors: Kazuaki
authors: K
authors: Nakano
authors: Masaki
authors: M
authors: Nagaya
authors: Toshihiro
authors: T
authors: Kobayashi
authors: Tomoyuki
authors: T
authors: Yamaguchi
authors: Ryo
authors: R
authors: Sumazaki
authors: Leonard A
authors: LA
authors: Herzenberg
authors: Hiromitsu
authors: H
authors: Nakauchi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D021522:Bioartificial Organs; D001755:Blastocyst / Q000166:cytology*; D019976:Cloning, Organism / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D010179:Pancreas; D013552:Swine / Q000196:embryology* / Q000235:genetics