title: Chitosan-assisted differentiation of porcine adipose tissue-derived stem cells into glucose-responsive insulin-secreting clusters.
abstract: The unique advantage of easy access and abundance make the adipose-derived stem cells (ADSCs) a promising system of multipotent cells for transplantation and regenerative medicine. Among the available sources, porcine ADSCs (pADSCs) deserve especial attention due to the close resemblance of human and porcine physiology, as well as for the upcoming availability of humanized porcine models. Here, we report on the isolation and conversion of pADSCs into glucose-responsive insulin-secreting cells. We used the stromal-vascular fraction of the dorsal subcutaneous adipose from 9-day-old male piglets to isolate pADSCs, and subjected the cells to an induction scheme for differentiation on chitosan-coated plates. This one-step procedure promoted differentiation of pADSCs into pancreatic islet-like clusters (PILC) that are characterized by the expression of a repertoire of pancreatic proteins, including pancreatic and duodenal homeobox (Pdx-1), insulin gene enhancer protein (ISL-1) and insulin. Upon glucose challenge, these PILC secreted high amounts of insulin in a dose-dependent manner. Our data also suggest that chitosan plays roles not only to enhance the differentiation potential of pADSCs, but also to increase the glucose responsiveness of PILCs. Our novel approach is, therefore, of great potential for transplantation-based amelioration of type 1 diabetes.
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei City, Taiwan, R.O.C.|Institute of Biotechnology, National Taiwan University, Taipei City, Taiwan.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Liu
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei City, Taiwan, R.O.C.
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei City, Taiwan, R.O.C.
authors.forename: Yuan-Yu
authors.initials: YY
authors.lastname: Lin
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei City, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei City, Taiwan, R.O.C.
authors.forename: Bing-Hsien
authors.initials: BH
authors.lastname: Liu
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei City, Taiwan, R.O.C.
authors.forename: Shiu-Chung
authors.initials: SC
authors.lastname: Wong
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei City, Taiwan.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei City, Taiwan, R.O.C.
authors.forename: Yun-Tsui
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Graduate Institute of Oral Biology, National Taiwan University, Taipei City, Taiwan.
authors.forename: Han-Yi E
authors.initials: HE
authors.lastname: Chou
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei City, Taiwan, R.O.C.|Institute of Biotechnology, National Taiwan University, Taipei City, Taiwan.
authors.forename: Shih-Torng
authors.identifier: http://orcid.org/0000-0002-9866-1776
authors.initials: ST
authors.lastname: Ding
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D048271:Chitosan / Q000494:pharmacology*; D003470:Culture Media; D004797:Enzyme-Linked Immunosorbent Assay; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D050151:Subcutaneous Fat / Q000166:cytology; D013552:Swine
chemical_list: D003470:Culture Media; D007328:Insulin; D048271:Chitosan