PMID- 27762664 OWN - NLM STAT- MEDLINE DCOM- 20171120 LR - 20220321 IS - 1937-335X (Electronic) IS - 1937-3341 (Print) IS - 1937-3341 (Linking) VI - 22 IP - 23-24 DP - 2016 Dec TI - Limited Immunogenicity of Human Induced Pluripotent Stem Cell-Derived Cartilages. PG - 1367-1375 AB - Articular cartilage damage does not spontaneously heal and could ultimately result in a loss of joint function. Damaged cartilage can be repaired with cell/tissue sources that are transplanted, however, autologous chondrocytes are limited in number as a cell source. Induced pluripotent stem cells (iPSCs) are a relatively new and abundant cell source and can be made from the patient, but at a considerable cost. Because cartilage is immunoprivileged tissue, allogeneic cartilages have been transplanted effectively without matching for human leukocyte antigen (HLA), but are difficult to acquire due to scarcity of donors. In this study, we examined the immunogenicity of human iPSC-derived cartilages (hiPS-Carts) in vitro to evaluate whether allogeneic hiPS-Carts can be a new cell/tissue source. The cells in hiPS-Carts expressed limited amounts of major histocompatibility complex (MHC) class I (HLA-ABC) and MHC class II (HLA-DRDQDP). Treatment with interferon gamma (IFNgamma) induced the expression of MHC class I, but not MHC class II in hiPS-Carts. A mixed lymphocyte reaction assay showed that hiPS-Carts stimulated the proliferation of neither T cells nor the activation of NK cells. Furthermore, hiPS-Carts suppressed the proliferation of T cells stimulated with interleukin 2 and phytohemagglutinin (PHA). Together with previously reported findings, these results suggest that hiPS-Carts are no more antigenic than human cartilage. Additionally, in combination with the fact that iPSCs are unlimitedly expandable and thus can supply unlimited amounts of iPS-Carts from even one iPSC line, they suggest that allogeneic hiPS-Carts are a candidate source for transplantation to treat articular cartilage damage. FAU - Kimura, Takeshi AU - Kimura T AD - 1 Cell Induction and Regulation Field, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University , Kyoto, Japan . AD - 2 Department of Pediatrics, Osaka University Graduate School of Medicine , Osaka, Japan . FAU - Yamashita, Akihiro AU - Yamashita A AD - 1 Cell Induction and Regulation Field, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University , Kyoto, Japan . FAU - Ozono, Keiichi AU - Ozono K AD - 2 Department of Pediatrics, Osaka University Graduate School of Medicine , Osaka, Japan . FAU - Tsumaki, Noriyuki AU - Tsumaki N AD - 1 Cell Induction and Regulation Field, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University , Kyoto, Japan . LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161031 PL - United States TA - Tissue Eng Part A JT - Tissue engineering. Part A JID - 101466659 RN - 0 (HLA Antigens) RN - 0 (IFNG protein, human) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - *Bioprosthesis MH - *Cartilage, Articular MH - HLA Antigens/*immunology MH - Humans MH - Induced Pluripotent Stem Cells/*immunology MH - Interferon-gamma/*immunology MH - Regeneration/immunology MH - T-Lymphocytes/*immunology PMC - PMC5175426 OTO - NOTNLM OT - allogeneic transplantation OT - articular cartilage OT - induced pluripotent stem (iPS) cells OT - regeneration COIS- Statement No competing financial interests exist. EDAT- 2016/11/01 06:00 MHDA- 2017/11/29 06:00 PMCR- 2016/12/01 CRDT- 2016/11/01 06:00 PHST- 2016/11/01 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2016/11/01 06:00 [entrez] PHST- 2016/12/01 00:00 [pmc-release] AID - 10.1089/ten.tea.2016.0189 [pii] AID - 10.1089/ten.TEA.2016.0189 [doi] PST - ppublish SO - Tissue Eng Part A. 2016 Dec;22(23-24):1367-1375. doi: 10.1089/ten.TEA.2016.0189. Epub 2016 Oct 31.