Dental pulp stem cells as a therapy for congenital entero-neuropathy
Abstract Hirschsprung’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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-10077-3 |
| _version_ | 1817976347447787520 |
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| author | Koichiro Yoshimaru Takayoshi Yamaza Shunichi Kajioka Soichiro Sonoda Yusuke Yanagi Toshiharu Matsuura Junko Yoshizumi Yoshinao Oda Naoko Iwata Chiho Takai Shinsuke Nakayama Tomoaki Taguchi |
| author_facet | Koichiro Yoshimaru Takayoshi Yamaza Shunichi Kajioka Soichiro Sonoda Yusuke Yanagi Toshiharu Matsuura Junko Yoshizumi Yoshinao Oda Naoko Iwata Chiho Takai Shinsuke Nakayama Tomoaki Taguchi |
| author_sort | Koichiro Yoshimaru |
| collection | DOAJ |
| description | Abstract Hirschsprung’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. |
| first_indexed | 2024-04-13T22:02:22Z |
| format | Article |
| id | doaj.art-ba81477fd4ea49168ccdc681b22efbdd |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T22:02:22Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ba81477fd4ea49168ccdc681b22efbdd2022-12-22T02:28:04ZengNature PortfolioScientific Reports2045-23222022-04-0112111310.1038/s41598-022-10077-3Dental pulp stem cells as a therapy for congenital entero-neuropathyKoichiro Yoshimaru0Takayoshi Yamaza1Shunichi Kajioka2Soichiro Sonoda3Yusuke Yanagi4Toshiharu Matsuura5Junko Yoshizumi6Yoshinao Oda7Naoko Iwata8Chiho Takai9Shinsuke Nakayama10Tomoaki Taguchi11Department of Pediatric Surgery, Kyushu University Graduate School of Medical SciencesDepartment of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental ScienceDepartment of Clinical Pharmacology, Kyushu University Graduate School of MedicineDepartment of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental ScienceDepartment of Pediatric Surgery, Kyushu University Graduate School of Medical SciencesDepartment of Pediatric Surgery, Kyushu University Graduate School of Medical SciencesDepartment of Oral and Maxillofacial Surgery, Fukuoka Dental CollegeDepartment of Anatomic Pathology, Kyushu University Graduate School of Medical SciencesDepartment of Cell Physiology, Nagoya University Graduate School of MedicineDepartment of Cell Physiology, Nagoya University Graduate School of MedicineDepartment of Cell Physiology, Nagoya University Graduate School of MedicineDepartment of Pediatric Surgery, Kyushu University Graduate School of Medical SciencesAbstract Hirschsprung’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.https://doi.org/10.1038/s41598-022-10077-3 |
| spellingShingle | Koichiro Yoshimaru Takayoshi Yamaza Shunichi Kajioka Soichiro Sonoda Yusuke Yanagi Toshiharu Matsuura Junko Yoshizumi Yoshinao Oda Naoko Iwata Chiho Takai Shinsuke Nakayama Tomoaki Taguchi Dental pulp stem cells as a therapy for congenital entero-neuropathy Scientific Reports |
| title | Dental pulp stem cells as a therapy for congenital entero-neuropathy |
| title_full | Dental pulp stem cells as a therapy for congenital entero-neuropathy |
| title_fullStr | Dental pulp stem cells as a therapy for congenital entero-neuropathy |
| title_full_unstemmed | Dental pulp stem cells as a therapy for congenital entero-neuropathy |
| title_short | Dental pulp stem cells as a therapy for congenital entero-neuropathy |
| title_sort | dental pulp stem cells as a therapy for congenital entero neuropathy |
| url | https://doi.org/10.1038/s41598-022-10077-3 |
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