Title:
Generation of Functional Organs from Pluripotent Stem Cells: Toward the Next Generation of Regenerative Medicine
Hiromitsu NAKAUCHI, M.D., Ph.D. 1,2
1 Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo
2 Japan Science Technology Agency, ERATO, Nakauchi Stem Cell and Organ Regeneration Project
Abstract:
Stem cell based regenerative medicine has been a focus of attention worldwide. In particular, recent development of the iPS cell technology has enabled generation of patient’s pluripotent stem cells (PSCs), opening up the way to regenerative medicine using patient’s own PSC-derived cells. However, current stem cell therapy mainly targets diseases that can be treated by cell transplantation, such as Parkinson’s disease or diabetes mellitus. The complexity of organogenesis hinders in vitro generation of organs derived from a patient’s PSCs, an ultimate goal of regenerative medicine. To address this issue, we hypothesized first that a niche for organogenesis is vacant in post-blastocyst mutant mouse embryos genetically precluded from development of a certain organ, and second that injected induced pluripotent stem cell (iPSC)-derived cells would colonize this niche, compensate for the developmental defect, and form a donor-induced organ in vivo . We tested this hypothesis using Pdx1-/- blastocysts (pancreatogenesis-disabled) and blastocyst complementation technique. When wild type rat iPSCs were injected into mousePdx1-/- blastocysts, defective cells were totally replaced and pancreas was formed almost entirely by injected rat iPSC-derived cells. Chimeric mice of Pdx1-/- genotype survived to adulthood without any sign of diabetes. Generation of organs using rat iPSCs and blastocyst complementation in vivo provides a new strategy for understanding organogenesis and a novel approach for organ supply.
References:
Kobayashi et al. Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell. 2010 3;142:787-99.
