title: Artificial islets from hybrid spheroids of three pancreatic cell lines.
abstract: Pancreatic islets have been the focus of recent studies exploring the pathologic mechanisms of diabetes mellitus as well as more effective and radical treatments for this disease. Islet transplantation is a promising therapeutic strategy; however, isolation of pancreatic islets for this purpose has been challenging, because the technique is time consuming and technically difficult, and tissue handling can be variable. Pseudo-islets can be used as an alternative to naïve islets, but require cellular sources or artificial materials. In this study, pancreas-derived cells were used to generate pseudo-islets. Because the pancreas is composed of a variety of cell types, namely α cells, β cells, δ cells, and other pancreatic cells that perform different functions, we used 3 different cell lines-NIT-1 (a β-cell line), α TC1 clone 6 (an α-cell line), and TGP52 (a pancreatic epithelial-like cell line)-which we cocultured in nonadhesive culture plates to produce hybrid cellular spheroids. These pseudo-islets had an oval shape and were morphologically similar to naïve islets; additionally, they expressed and secreted the pancreatic hormones insulin, glucagon, and somatostatin, as confirmed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. The results demonstrate that pseudo-islets that mimic naïve islets can be successfully generated by a coculture method. These artificial islets can potentially be used for in vitro tests related to diabetes mellitus, specifically, in drug discovery or for investigating pathology. Moreover, they can be useful for examining basic questions pertaining to cell-cell interactions and tissue development.
authors.affiliation: Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology (IBST), Konkuk University, Seoul, Korea.
authors.forename: Y H
authors.initials: YH
authors.lastname: Jo
authors.affiliation: Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology (IBST), Konkuk University, Seoul, Korea.
authors.forename: I J
authors.initials: IJ
authors.lastname: Jang
authors.affiliation: Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology (IBST), Konkuk University, Seoul, Korea.
authors.forename: J G
authors.initials: JG
authors.lastname: Nemeno
authors.affiliation: Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology (IBST), Konkuk University, Seoul, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.affiliation: Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology (IBST), Konkuk University, Seoul, Korea.
authors.forename: B Y
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology (IBST), Konkuk University, Seoul, Korea.
authors.forename: B M
authors.initials: BM
authors.lastname: Nam
authors.affiliation: Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology (IBST), Konkuk University, Seoul, Korea.
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.affiliation: Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology (IBST), Konkuk University, Seoul, Korea.
authors.forename: K M
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology (IBST), Konkuk University, Seoul, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Project Leader of Advanced Medical Research Center, Yokohama City University, Yokohama, Japan; PRESTO, Japan Science and Technology Agency, Kawaguchi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takebe
authors.affiliation: Research Institute for Transplantation, Department of Transplantation Surgery, Yonsei University Health System, Seoul, Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology (IBST), Konkuk University, Seoul, Korea. Electronic address: jeongik@konkuk.ac.kr.
authors.forename: J I
authors.initials: JI
authors.lastname: Lee
mesh_terms: D000818:Animals; D021522:Bioartificial Organs; D002450:Cell Communication; D045744:Cell Line, Tumor; D048430:Cell Shape; D018920:Coculture Techniques; D005786:Gene Expression Regulation; D005934:Glucagon / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D013004:Somatostatin; D005934:Glucagon