Stem cell properties of human clonal salivary gland stem cells are enhanced by three-dimensional priming culture in nanofibrous microwells
Abstract Background Three-dimensional (3D) cultures recapitulate the microenvironment of tissue-resident stem cells and enable them to modulate their properties. We determined whether salivary gland-resident stem cells (SGSCs) are primed by a 3D spheroid culture prior to treating irradiation-induced...
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| Format: | Article |
| Language: | English |
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BMC
2018-03-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13287-018-0829-x |
| _version_ | 1819179644472000512 |
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| author | Hyun-Soo Shin Songyi Lee Hye Jin Hong Young Chang Lim Won-Gun Koh Jae-Yol Lim |
| author_facet | Hyun-Soo Shin Songyi Lee Hye Jin Hong Young Chang Lim Won-Gun Koh Jae-Yol Lim |
| author_sort | Hyun-Soo Shin |
| collection | DOAJ |
| description | Abstract Background Three-dimensional (3D) cultures recapitulate the microenvironment of tissue-resident stem cells and enable them to modulate their properties. We determined whether salivary gland-resident stem cells (SGSCs) are primed by a 3D spheroid culture prior to treating irradiation-induced salivary hypofunction using in-vitro coculture and in-vivo transplant models. Methods 3D spheroid-derived SGSCs (SGSCs3D) were obtained from 3D culture in microwells consisting of a nanofiber bottom and cell-repellent hydrogel walls, and were examined for salivary stem or epithelial gene/protein expression, differentiation potential, and paracrine secretory function compared with monolayer-cultured SGSCs (SGSCs2D) in vitro and in vivo. Results SGSCs3D expressed increased salivary stem cell markers (LGR5 and THY1) and pluripotency markers (POU5F1 and NANOG) compared with SGSCs2D. Also, SGSCs3D exhibited enhanced potential to differentiate into salivary epithelial cells upon differentiation induction and increased paracrine secretion as compared to SGSCs2D. Wnt signaling was activated by 3D spheroid formation in the microwells and suppression of the Wnt/β-catenin pathway led to reduced stemness of SGSCs3D. Enhanced radioprotective properties of SGSCs3D against radiation-induced salivary hypofunction was confirmed by an organotypic 3D coculture and in-vivo transplantation experiments. Conclusion The 3D spheroid culture of SGSCs in nanofibrous microwells promotes stem cell properties via activation of Wnt signaling. This may contribute to SGSC priming prior to regenerative therapy to restore salivary hypofunction after radiotherapy. |
| first_indexed | 2024-12-22T22:01:43Z |
| format | Article |
| id | doaj.art-eac3977f57d243efb272c87ba6236bc1 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-22T22:01:43Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-eac3977f57d243efb272c87ba6236bc12022-12-21T18:11:07ZengBMCStem Cell Research & Therapy1757-65122018-03-019111510.1186/s13287-018-0829-xStem cell properties of human clonal salivary gland stem cells are enhanced by three-dimensional priming culture in nanofibrous microwellsHyun-Soo Shin0Songyi Lee1Hye Jin Hong2Young Chang Lim3Won-Gun Koh4Jae-Yol Lim5Department of Otorhinolaryngology, Gangnam Severance Hospital, Yonsei University College of MedicineDepartment of Otorhinolaryngology, Gangnam Severance Hospital, Yonsei University College of MedicineDepartment of Chemical and Biomolecular Engineering, Yonsei UniversityDepartment of Otorhinolaryngology, Head and Neck Surgery, Konkuk University School of MedicineDepartment of Chemical and Biomolecular Engineering, Yonsei UniversityDepartment of Otorhinolaryngology, Gangnam Severance Hospital, Yonsei University College of MedicineAbstract Background Three-dimensional (3D) cultures recapitulate the microenvironment of tissue-resident stem cells and enable them to modulate their properties. We determined whether salivary gland-resident stem cells (SGSCs) are primed by a 3D spheroid culture prior to treating irradiation-induced salivary hypofunction using in-vitro coculture and in-vivo transplant models. Methods 3D spheroid-derived SGSCs (SGSCs3D) were obtained from 3D culture in microwells consisting of a nanofiber bottom and cell-repellent hydrogel walls, and were examined for salivary stem or epithelial gene/protein expression, differentiation potential, and paracrine secretory function compared with monolayer-cultured SGSCs (SGSCs2D) in vitro and in vivo. Results SGSCs3D expressed increased salivary stem cell markers (LGR5 and THY1) and pluripotency markers (POU5F1 and NANOG) compared with SGSCs2D. Also, SGSCs3D exhibited enhanced potential to differentiate into salivary epithelial cells upon differentiation induction and increased paracrine secretion as compared to SGSCs2D. Wnt signaling was activated by 3D spheroid formation in the microwells and suppression of the Wnt/β-catenin pathway led to reduced stemness of SGSCs3D. Enhanced radioprotective properties of SGSCs3D against radiation-induced salivary hypofunction was confirmed by an organotypic 3D coculture and in-vivo transplantation experiments. Conclusion The 3D spheroid culture of SGSCs in nanofibrous microwells promotes stem cell properties via activation of Wnt signaling. This may contribute to SGSC priming prior to regenerative therapy to restore salivary hypofunction after radiotherapy.http://link.springer.com/article/10.1186/s13287-018-0829-xSalivary glandsXerostomiaSpheroidMicropatterned nanofibrous scaffoldsWnt |
| spellingShingle | Hyun-Soo Shin Songyi Lee Hye Jin Hong Young Chang Lim Won-Gun Koh Jae-Yol Lim Stem cell properties of human clonal salivary gland stem cells are enhanced by three-dimensional priming culture in nanofibrous microwells Stem Cell Research & Therapy Salivary glands Xerostomia Spheroid Micropatterned nanofibrous scaffolds Wnt |
| title | Stem cell properties of human clonal salivary gland stem cells are enhanced by three-dimensional priming culture in nanofibrous microwells |
| title_full | Stem cell properties of human clonal salivary gland stem cells are enhanced by three-dimensional priming culture in nanofibrous microwells |
| title_fullStr | Stem cell properties of human clonal salivary gland stem cells are enhanced by three-dimensional priming culture in nanofibrous microwells |
| title_full_unstemmed | Stem cell properties of human clonal salivary gland stem cells are enhanced by three-dimensional priming culture in nanofibrous microwells |
| title_short | Stem cell properties of human clonal salivary gland stem cells are enhanced by three-dimensional priming culture in nanofibrous microwells |
| title_sort | stem cell properties of human clonal salivary gland stem cells are enhanced by three dimensional priming culture in nanofibrous microwells |
| topic | Salivary glands Xerostomia Spheroid Micropatterned nanofibrous scaffolds Wnt |
| url | http://link.springer.com/article/10.1186/s13287-018-0829-x |
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