caa a22 4500 445889209 CHVBK 20180317145610.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s00535-010-0320-7 doi (NATIONALLICENCE)springer-10.1007/s00535-010-0320-7 Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat [Elektronische Daten] [Hiroki Tanaka, Yoshiaki Arimura, Takashi Yabana, Akira Goto, Masayo Hosokawa, Kanna Nagaishi, Kentaro Yamashita, Hiroyuki Yamamoto, Yasushi Sasaki, Mineko Fujimiya, Kohzoh Imai, Yasuhisa Shinomura] Background: Although mounting evidence implicates mesenchymal stem cells (MSCs) in intestinal tissue repair, uncertainty remains concerning the distribution, function, and fate of repopulating MSCs in recipient colonic tissues. Therefore, we investigated the role of transplanted MSCs in the repair phase of DSS colitis. Methods: LacZ-labeled rat MSCs were transplanted into rats with colitis induced by 4% DSS on day 2. Regular water replaced the DSS solution on day 6. Therapeutic effect was evaluated on day 9 by clinicopathologic and growth factor/cytokine expression profiles. We analyzed the Notch signaling pathway by Western blotting and characterized immunofluorescence of lacZ-labeled MSCs with confocal laser microscopy. In vivo differentiation of MSC was confirmed by transmission electron microscopy (TEM). Results: Recovery of colitis was modestly but significantly promoted by MSC transplantation due to proceeding cell cycle and inhibiting apoptosis in the epithelia. Tgfa mRNA expression increased significantly, while Notch signaling was inhibited in the colonic tissues with MSC transplantation. β-Galactosidase-positive cells, which expressed α-SMA, desmin, and vimentin, were infrequently detected in the lamina propria stroma. DSS exposure in vitro proved to be the most potent inducer for α-SMA in MSCs where TEM demonstrated myogenic lineage differentiation. Conclusions: We found that MSCs transplantation modestly promoted the repair of DSS colitis. The donor-derived MSCs were likely reprogrammed to differentiate to myogenic lineage cells by cues from the micro milieu. Further characterization of these cells is warranted as a basis for applying cell-based therapy for inflammatory bowel disease. Springer, 2010 Mesenchymal stem cell (MSC) nationallicence Myogenic lineage differentiation, dextran sulfate sodium (DSS) colitis nationallicence Recovery phase nationallicence Inflammatory bowel disease (IBD) nationallicence Tanaka Hiroki First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut Arimura Yoshiaki First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut Yabana Takashi First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut Goto Akira First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut Hosokawa Masayo First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut Nagaishi Kanna First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut Yamashita Kentaro First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut Yamamoto Hiroyuki First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut Sasaki Yasushi Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan aut Fujimiya Mineko Department of Anatomy, Sapporo Medical University, Sapporo, Japan aut Imai Kohzoh Sapporo Medical University, Sapporo, Japan aut Shinomura Yasuhisa First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut Journal of Gastroenterology Springer Japan 46/2(2011-02-01), 143-152 0944-1174 46:2<143 2011 46 535 https://doi.org/10.1007/s00535-010-0320-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-010-0320-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tanaka Hiroki First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut NATIONALLICENCE 700 1- Arimura Yoshiaki First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut NATIONALLICENCE 700 1- Yabana Takashi First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut NATIONALLICENCE 700 1- Goto Akira First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut NATIONALLICENCE 700 1- Hosokawa Masayo First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut NATIONALLICENCE 700 1- Nagaishi Kanna First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut NATIONALLICENCE 700 1- Yamashita Kentaro First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut NATIONALLICENCE 700 1- Yamamoto Hiroyuki First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut NATIONALLICENCE 700 1- Sasaki Yasushi Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan aut NATIONALLICENCE 700 1- Fujimiya Mineko Department of Anatomy, Sapporo Medical University, Sapporo, Japan aut NATIONALLICENCE 700 1- Imai Kohzoh Sapporo Medical University, Sapporo, Japan aut NATIONALLICENCE 700 1- Shinomura Yasuhisa First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/2(2011-02-01), 143-152 0944-1174 46:2<143 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer