We have long been working on various large animal models in addition to mice.
Our models include non-human primates, sheeps and pigs, and research focuses have been hematopoietic stem cell transplantation and gene therapy (Hanazono, Stem Cells, 2001; Gene Ther, 2002), prion diseases (Hagiwara, PLoS One, 2019他), differentiation and long-term maintenance of hematopoietic stem cell in xenotransplantation setting(Sasaki, Transplantation, 2005), immunodeficient pigs and germ-free/humanized microbiota pigs
We are extensively working on developing a novel genome-editing therapy to correct genetic mutation in hematopoietic stem cells.
We are also studying general and cell-type specific DNA repair mechanisms.
It is still challenging to generate hematopoietic stem cells from human iPS cells. We are trying to overcome the issue using a sheep to provide essential niche.
We have reported human hematopoietic stem cells can engraft and maintain long-term in sheep bone marrow after transplantation into fetal sheep liver (Abe, Exp Hematol 2011; Exp Hematol, 2012; Exp Anim, 2014). We also fond that human iPS-derivatives turn into hematopoietic stem cells in vivo (Abe, in preparation).
A pig eats anything that human eats and it's gustrointestinal truct is very similar to that of human in anatomy and physilogy. Therefore, a pig can be a good animal model for microbiology study. As we are able to make and maintain pigs completely germ free, we transplanted human feces to the germ free pig to generate a pig with humanized microbiota. We are examining time course of microbiota and effects of feedings.
We aim to elucidate molecular mechanisms regulating cardiomyocyte maturation.
With an efficient, directed cardiac differentiation method, we are able to obtain cardiomyocytes from pluripotent stem cells. However, such cardiomyocytes were immature as fetal cardiomyocytes, which limits the potential of stem cell derived cardiomyocytes being a platform to study human heart diseases.
We will elucidate the molecular mechanisms and provide a platform to recaptulate human heart diseases in vitro.
We are working on to model cardiac myopathy and malformation in vivo and/or in vitro.
In a collabolation with Drs. Koitabashi (Gunma U), Nishizono (Max Planck Florida), and other researchers of Jichi Medical Unviersity, we are generating animal models harvoring SNVs that found in congenital heart diseases and cardiac myopathy.
As a part of an AMED-sponsored project, we are establishing a number of patient-derived iPS cell lines for mitochondrial diseases and neural disorders in collabolation with Dr. Murayama (Chiba Children's Hospital) and our pediatrics department.
To analyze the physiological function of iPS cell-derived cardiomyocytes, we are developing new tools and techniques for sarcomere shortining with live-imaging, which may facilitate the cardiomyopathy study.
These studies will provide novel perspectives in heart diseases.
