1: Direct In Vivo Reprogramming with Sendai Virus Vectors Improves Cardiac Function after Myocardial Infarction
Science of the Month - February 2018
Cell Stem Cell.
2018 Jan 4;22(1):91-103.e5. doi: 10.1016
Kazutaka Miyamoto, Mizuha Akiyama, Fumiya Tamura, Mari Isomi, Hiroyuki Yamakawa, Taketaro Sadahiro, Naoto Muraoka, Hidenori Kojima, Sho Haginiwa, Shota Kurotsu, Hidenori Tani, Li Wang, Li Qian, Makoto Inoue, Yoshinori Ide, Junko Kurokawa, Tsunehisa Yamamoto, Tomohisa Seki, Ryo Aeba, Hiroyuki Yamagishi, Keiichi Fukuda, Masaki Ieda
We have previously reported that cardiac muscle cells can be directly generated by introducing three myogenic induction genes into cardiac fibroblasts using retroviral vectors as gene carriers. However, conventional methods had two challenges: 1) the potential for damage to the cell's genome because the three genes are integrated by the viral vector during myogenic induction, and 2) low myogenic induction efficiency and the long time required to generate cardiac muscle. In this study, the authors developed a Sendai virus vector that simultaneously expresses the three myogenic induction genes. Using this, we succeeded in efficiently and rapidly generating cardiac muscle cells directly from mouse and human fibroblasts in culture dishes without damaging the genome. Furthermore, we found that when the myogenic-inducing Sendai virus vector was introduced into the hearts of a mouse myocardial infarction model, myocardial regeneration began one week after treatment, and cardiac function improved one month later. From the above, we have succeeded for the first time in the world in directly generating cardiac muscle efficiently and in a short period without damaging the cell's genome, achieving cardiac regeneration. In the future, this is expected to be applied to regenerative medicine for various heart diseases, including myocardial infarction and dilated cardiomyopathy.
(Department of Cardiology. Kazutaka Miyamoto, 84th; Masaki Ieda, 74th)
2: Ectopic colonization of oral bacteria in the intestine drives T(H)1 cell induction and inflammation
SCIENCE
358 (6361):359-+; 10.1126/science.aan4526 OCT 20 2017
Atarashi Koji, Suda Wataru, Luo Chengwei, Kawaguchi Takaaki, Motoo Iori, Narushima Seiko, Kiguchi Yuya, Yasuma Keiko, Watanabe Eiichiro, Tanoue Takeshi, Thaiss Christoph A., Sato Mayuko, Toyooka Kiminori, Said Heba S., Yamagami Hirokazu, Rice Scott A., Gevers Dirk, Johnson Ryan C., Segre Julia A., Chen Kong, Kolls Jay K., Elinav Eran, Morita Hidetoshi, Xavier Ramnik J., Hattori Masahira, Honda Kenya
Oral commensal bacteria are swallowed in large quantities with saliva every day, but they do not normally colonize the intestinal tract. However, it has been reported that a large number of oral bacteria colonize the intestinal tracts of patients with inflammatory bowel disease and liver cirrhosis. We hypothesized that there are oral bacteria that activate the immune system by ectopically colonizing the intestine, and we decided to search for such bacteria. As a result of orally administering saliva from Crohn's disease patients to germ-free mice and analyzing the immune cells in the intestinal tract, we found that when saliva from a certain patient was administered, CD4-positive helper T cells (TH1 cells) that produce interferon-gamma (IFN-γ) increased in the intestine. We cultured the bacteria that had colonized the intestine and isolated eight species of bacteria. Of the eight bacterial species, we found that a bacterium belonging to the genus *Klebsiella* was responsible for inducing TH1 cells. We also found that this *Klebsiella* bacterium has the effect of exacerbating an enteritis model. Furthermore, we found that when this oral-derived *Klebsiella* was administered to mice with normal intestinal bacteria, it did not colonize the intestine, and only colonized when the intestinal microbiota was disturbed, such as by the use of antibiotics. This suggests that excessive administration of antibiotics may cause colonization of *Klebsiella* species in the intestinal tract even in healthy individuals, and we concluded that the use of antibiotics should be done with great caution.
(Kenya Honda, Professor of Microbiology and Immunology, 73rd equivalent)