@article{f5029ac7d4624984a3fca590ad33ad00,
title = "Dental pulp stem cells as a therapy for congenital entero-neuropathy",
abstract = "Hirschsprung{\textquoteright}s disease is a congenital entero-neuropathy that causes chronic constipation and intestinal obstruction. New treatments for entero-neuropathy are needed because current surgical strategies have limitations5. Entero-neuropathy results from enteric nervous system dysfunction due to incomplete colonization of the distal intestine by neural crest-derived cells. Impaired cooperation between the enteric nervous system and intestinal pacemaker cells may also contribute to entero-neuropathy. Stem cell therapy to repair these multiple defects represents a novel treatment approach. Dental pulp stem cells derived from deciduous teeth (dDPSCs) are multipotent cranial neural crest-derived cells, but it remains unknown whether dDPSCs have potential as a new therapy for entero-neuropathy. Here we show that intravenous transplantation of dDPSCs into the Japanese Fancy-1 mouse, an established model of hypoganglionosis and entero-neuropathy, improves large intestinal structure and function and prolongs survival. Intravenously injected dDPSCs migrate to affected regions of the intestine through interactions between stromal cell-derived factor-1α and C-X-C chemokine receptor type-4. Transplanted dDPSCs differentiate into both pacemaker cells and enteric neurons in the proximal colon to improve electrical and peristaltic activity, in addition to their paracrine effects. Our findings indicate that transplanted dDPSCs can differentiate into different cell types to correct entero-neuropathy-associated defects.",
author = "Koichiro Yoshimaru and Takayoshi Yamaza and Shunichi Kajioka and Soichiro Sonoda and Yusuke Yanagi and Toshiharu Matsuura and Junko Yoshizumi and Yoshinao Oda and Naoko Iwata and Chiho Takai and Shinsuke Nakayama and Tomoaki Taguchi",
note = "Funding Information: The authors are grateful to Ratih Yuniartha, Tomoko Yamazaki, Kozue Urata, Rie Funatsu (Department of Pediatric Surgery), Jumi Matsumoto (Department of Anatomic Pathology) and Erika Tomoda (Department of Molecular Cell Biology and Oral Anatomy, Graduate School of Dental Science, Kyushu University, Japan) for technical assistance in histological studies, enzyme assays, gene-expression studies, in vivo and ex vivo imaging and animal management, to Eiji Mitate (Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University, Japan) for supporting the analysis of the MEA data recorded using the MED64 system, and to Maya Hayashi for data curation and visualization of therapeutic effects. The authors are also grateful to Haruyoshi Yamaza for collecting teeth samples. The authors thank OXMEDCOMMS ( www.oxmedcomms.com ) for assistance with the preparation of the manuscript. This work was supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion Science (JSPS): 25253094 (T.T., K.Y, T.Y., S.K.), 15K10922 (K.Y.) and 19H03558 (N.I., C.T., S.N.); Grant-in-Aid for Challenging Exploratory Research Project from JSPS 25670744 (T.T.); Research grant from the Ministry of Health, Labor and Welfare H26-040 (T.T.); Research grant from the Japan Agency for Medical Research and Development (AMED) 16ek0210037h0003 (S.N.); Research grant The Japan Foundation for Pediatric Research 15-002 (K.Y.); Research grant from Suzuken Memorial Foundation (S.N., N.I., C.T.). Funding Information: The authors are grateful to Ratih Yuniartha, Tomoko Yamazaki, Kozue Urata, Rie Funatsu (Department of Pediatric Surgery), Jumi Matsumoto (Department of Anatomic Pathology) and Erika Tomoda (Department of Molecular Cell Biology and Oral Anatomy, Graduate School of Dental Science, Kyushu University, Japan) for technical assistance in histological studies, enzyme assays, gene-expression studies, in vivo and ex vivo imaging and animal management, to Eiji Mitate (Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University, Japan) for supporting the analysis of the MEA data recorded using the MED64 system, and to Maya Hayashi for data curation and visualization of therapeutic effects. The authors are also grateful to Haruyoshi Yamaza for collecting teeth samples. The authors thank OXMEDCOMMS (www.oxmedcomms.com) for assistance with the preparation of the manuscript. This work was supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion Science (JSPS): 25253094 (T.T., K.Y, T.Y., S.K.), 15K10922 (K.Y.) and 19H03558 (N.I., C.T., S.N.); Grant-in-Aid for Challenging Exploratory Research Project from JSPS 25670744 (T.T.); Research grant from the Ministry of Health, Labor and Welfare H26-040 (T.T.); Research grant from the Japan Agency for Medical Research and Development (AMED) 16ek0210037h0003 (S.N.); Research grant The Japan Foundation for Pediatric Research 15-002 (K.Y.); Research grant from Suzuken Memorial Foundation (S.N., N.I., C.T.). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41598-022-10077-3",
language = "English",
volume = "12",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}