OKANO Teruo
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position  
Article types Original article
Language English
Peer review Peer reviewed
Title Improvement of the therapeutic capacity of insulin-producing cells trans-differentiated from human liver cells using engineered cell sheet.
Journal Formal name：Stem cell research & therapy
Abbreviation：Stem Cell Res Ther
ISSN code：17576512/17576512
Domestic / ForeginForegin
Volume, Issue, Page 12(1),pp.3
Author and coauthor Lee Yu Na†, Yi Hye-Jin, Seo Eun Hye, Oh Jooyun, Lee Song, Ferber Sarah, Okano Teruo, Shim In Kyong*, Kim Song Cheol*
Publication date 2021/01/06
Summary BACKGROUND:Although pancreatic islet transplantation therapy is ideal for diabetes patients, several hurdles have prevented it from becoming a standard treatment, including donor shortage and low engraftment efficacy. In this study, we prepared insulin-producing cells trans-differentiated from adult human liver cells as a new islet source. Also, cell sheet formation could improve differentiation efficiency and graft survival.
METHODS:Liver cells were expanded in vitro and trans-differentiated to IPCs using adenovirus vectors carrying human genes for PDX1, NEUROD1, and MAFA. IPCs were seeded on temperature-responsive culture dishes to form cell sheets. Differentiation efficiency was confirmed by ß cell-specific gene expression, insulin production, and immunohistochemistry. IPC suspension was injected by portal vein (PV), and IPC sheet was transplanted on the liver surface of the diabetic nude mouse. The therapeutic effect of IPC sheet was evaluated by comparing blood glucose control, weight gain, histological evaluation, and hepatotoxicity with IPC injection group. Also, cell biodistribution was assessed by in vivo/ex vivo fluorescence image tagging.RESULTS:Insulin gene expression and protein production were significantly increased on IPC sheets compared with those in IPCs cultured on conventional culture dishes. Transplanted IPC sheets displayed significantly higher engraftment efficiency and fewer transplanted cells in other organs than injected IPCs, and also lower liver toxicity, improved blood glucose levels, and weight gain. Immunohistochemical analyses of liver tissue revealed positive staining for PDX1 and insulin at 1, 2, and 4 weeks after IPC transplantation.
DOI 10.1186/s13287-020-02080-0
PMID 33407888