Development of Bifunctional Three-Dimensional Cysts from Chemically Induced Liver Progenitors
Chemically induced liver progenitors (CLiPs) have promising applications in liver regenerative medicine. Three-dimensional (3D) structures generated from liver progenitor cells possess wide applications in cell transplantation, disease model, and drug testing. Here, we report on the spontaneous form...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/3975689 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832558479436414976 |
|---|---|
| author | Yu Huang Yusuke Sakai Takanobu Hara Takeshi Katsuda Takahiro Ochiya Tomohiko Adachi Masaaki Hidaka Wei-Li Gu Susumu Eguchi |
| author_facet | Yu Huang Yusuke Sakai Takanobu Hara Takeshi Katsuda Takahiro Ochiya Tomohiko Adachi Masaaki Hidaka Wei-Li Gu Susumu Eguchi |
| author_sort | Yu Huang |
| collection | DOAJ |
| description | Chemically induced liver progenitors (CLiPs) have promising applications in liver regenerative medicine. Three-dimensional (3D) structures generated from liver progenitor cells possess wide applications in cell transplantation, disease model, and drug testing. Here, we report on the spontaneous formation of 3D cystic structures comprising maturing rat CLiPs on gelatin-coated dishes. Our 3D cysts contained Alb+/+CK19+/− and Ck19+/+Alb+/− cells. These cell types gradually diverged into specialized mature cells, as demonstrated by the expression of mature biliary markers (Cftr, Ae2, and Aqp1) and hepatic markers (Alb and Mrp2). The 3D cysts also expressed functional multidrug resistance protein 1 (Mdr1), as indicated by epithelial efflux of rhodamine. Furthermore, we observed bile canaliculi functions between hepatocytes and cholyl-lysyl-fluorescein extrusions, indicating that the functional characteristics of 3D cysts and active bile salt export pump (Bsep) transporters were intact. Thus, our study revealed a natural characteristic of rat CLiPs to spontaneously form 3D cystic structures accompanied with cell maturation in vitro, offering a platform for studies of liver development and drug screening. |
| format | Article |
| id | doaj-art-c8c0aa980d8b43d6b2d4967bc00ef740 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-c8c0aa980d8b43d6b2d4967bc00ef7402025-02-03T01:32:15ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/39756893975689Development of Bifunctional Three-Dimensional Cysts from Chemically Induced Liver ProgenitorsYu Huang0Yusuke Sakai1Takanobu Hara2Takeshi Katsuda3Takahiro Ochiya4Tomohiko Adachi5Masaaki Hidaka6Wei-Li Gu7Susumu Eguchi8Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanDivision of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDivision of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanDepartment of Hepato-Pancreato-Biliary Surgery, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, ChinaDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanChemically induced liver progenitors (CLiPs) have promising applications in liver regenerative medicine. Three-dimensional (3D) structures generated from liver progenitor cells possess wide applications in cell transplantation, disease model, and drug testing. Here, we report on the spontaneous formation of 3D cystic structures comprising maturing rat CLiPs on gelatin-coated dishes. Our 3D cysts contained Alb+/+CK19+/− and Ck19+/+Alb+/− cells. These cell types gradually diverged into specialized mature cells, as demonstrated by the expression of mature biliary markers (Cftr, Ae2, and Aqp1) and hepatic markers (Alb and Mrp2). The 3D cysts also expressed functional multidrug resistance protein 1 (Mdr1), as indicated by epithelial efflux of rhodamine. Furthermore, we observed bile canaliculi functions between hepatocytes and cholyl-lysyl-fluorescein extrusions, indicating that the functional characteristics of 3D cysts and active bile salt export pump (Bsep) transporters were intact. Thus, our study revealed a natural characteristic of rat CLiPs to spontaneously form 3D cystic structures accompanied with cell maturation in vitro, offering a platform for studies of liver development and drug screening.http://dx.doi.org/10.1155/2019/3975689 |
| spellingShingle | Yu Huang Yusuke Sakai Takanobu Hara Takeshi Katsuda Takahiro Ochiya Tomohiko Adachi Masaaki Hidaka Wei-Li Gu Susumu Eguchi Development of Bifunctional Three-Dimensional Cysts from Chemically Induced Liver Progenitors Stem Cells International |
| title | Development of Bifunctional Three-Dimensional Cysts from Chemically Induced Liver Progenitors |
| title_full | Development of Bifunctional Three-Dimensional Cysts from Chemically Induced Liver Progenitors |
| title_fullStr | Development of Bifunctional Three-Dimensional Cysts from Chemically Induced Liver Progenitors |
| title_full_unstemmed | Development of Bifunctional Three-Dimensional Cysts from Chemically Induced Liver Progenitors |
| title_short | Development of Bifunctional Three-Dimensional Cysts from Chemically Induced Liver Progenitors |
| title_sort | development of bifunctional three dimensional cysts from chemically induced liver progenitors |
| url | http://dx.doi.org/10.1155/2019/3975689 |
| work_keys_str_mv | AT yuhuang developmentofbifunctionalthreedimensionalcystsfromchemicallyinducedliverprogenitors AT yusukesakai developmentofbifunctionalthreedimensionalcystsfromchemicallyinducedliverprogenitors AT takanobuhara developmentofbifunctionalthreedimensionalcystsfromchemicallyinducedliverprogenitors AT takeshikatsuda developmentofbifunctionalthreedimensionalcystsfromchemicallyinducedliverprogenitors AT takahiroochiya developmentofbifunctionalthreedimensionalcystsfromchemicallyinducedliverprogenitors AT tomohikoadachi developmentofbifunctionalthreedimensionalcystsfromchemicallyinducedliverprogenitors AT masaakihidaka developmentofbifunctionalthreedimensionalcystsfromchemicallyinducedliverprogenitors AT weiligu developmentofbifunctionalthreedimensionalcystsfromchemicallyinducedliverprogenitors AT susumueguchi developmentofbifunctionalthreedimensionalcystsfromchemicallyinducedliverprogenitors |