title: Long-term viability of transplanted hybrid cellular spheroids within chondrocyte sheets.
abstract: Encapsulation of transplanted cells within an immunoisolating membrane may provide a new strategy for protecting these cells from recipient immune responses without the use of immunosuppressive drugs. We have previously reported a novel concept of immunoisolation and immunodelusion using recipient cells instead of traditional artificial materials. We developed a chondrocyte sheeting immunodelusive immunoisolated bioartificial pancreas (CSI-BAP) that would enable transplantation of cells across allogeneic and xenogeneic barriers without the cells being recognized as donor cells and without the need for immunosuppression. Recently, we have constructed hybrid cellular spheroids (HCSs) containing cells from two different cell lines (RIN-5F, an insulin-secreting cell line, and Hep-G2, a hepatocellular carcinoma cell line) to enhance the function and biocompatibility of the HCSs. These HCSs were then encapsulated with multiple layers of chondrocyte sheets obtained from the auricular cartilage of Sprague-Dawley (SD) rats. The in vitro ability of the CSI-BAP to secrete insulin was tested before transplantation. Histological evaluation of CSI-BAP chondrocyte microencapsulated immunoisolated islet morphology and viability of allogeneic or xenogeneic cell lines was performed 100 days after the CSI-BAP was transplanted into SD rats. Morphological evaluations revealed good viability of the islets and progression of islet encapsulation. In vitro insulin secretion from the CSI-BAP was well maintained. Additionally, insulin and albumin secretion from the CSI-BAP was confirmed by in vivo immunohistochemical examination. Moreover, the cell lines transplanted into the subcutaneous space in the form of HCSs within the chondrocyte sheets showed good viability of more than 100 days and sustained insulin and albumin secreting ability.
authors.affiliation: Department of Biomedical Science and Technology, Regenerative Medicine Laboratory, Konkuk University, Seoul, South Korea.
authors.forename: J I
authors.initials: JI
authors.lastname: Lee
authors.forename: J Y
authors.initials: JY
authors.lastname: Kim
authors.forename: H W
authors.initials: HW
authors.lastname: Kim
authors.forename: S J
authors.initials: SJ
authors.lastname: Bae
authors.forename: D J
authors.initials: DJ
authors.lastname: Joo
authors.forename: K H
authors.initials: KH
authors.lastname: Huh
authors.forename: Y H
authors.initials: YH
authors.lastname: Fang
authors.forename: J H
authors.initials: JH
authors.lastname: Jeong
authors.forename: M S
authors.initials: MS
authors.lastname: Kim
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D021522:Bioartificial Organs; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival; D019902:Chondrocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D018920:Coculture Techniques; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009368:Neoplasm Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018874:Spheroids, Cellular; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods
chemical_list: D000418:Albumins; D007328:Insulin