PMID- 20795757 OWN - NLM STAT- MEDLINE DCOM- 20110606 LR - 20180629 IS - 1477-2566 (Electronic) IS - 1465-3249 (Linking) VI - 13 IP - 3 DP - 2011 Mar TI - Adipose tissue-derived stem cells show both immunogenic and immunosuppressive properties after chondrogenic differentiation. PG - 310-7 LID - 10.3109/14653249.2010.504769 [doi] AB - BACKGROUND AIMS: The chondrogenic differentiation potential of mesenchymal stromal cells (MSC), as well as their immunosuppressive properties, have been studied extensively. So far, only a few studies have addressed the question of whether MSC still retain their immunosuppressive qualities after transdifferentiation. In particular, the expression of immunogenic markers, such as human leukocyte antigen (HLA)-DR, after differentiation has never been investigated. METHODS: Chondrogenic transdifferentiation was induced in human adipose tissue-derived stem cell (ADSC) pellet cultures derived from 10 different patients, using 10 ng/mL transforming growth factor (TGF)-beta3. Samples were harvested over a time-course of 28 days and analyzed by immunohistochemistry and reverse transcription (RT)-polymerase chain reaction (PCR). The cytokine levels in the supernatants of the samples were measured semi-quantitatively by dot-blots and quantitatively by enzyme-linked immunosorbant assays (ELISA). RESULTS: Undifferentiated ADSC were negative for chondrogenic markers, as well as HLA-ABC and HLA-DR epitopes in immunofluorescence. In contrast, TGF-beta3-induced pellet cultures showed both expression of chondrogenic differentiation markers, such as transcription factor 9 (Sox 9), collagen type IIa and aggrecan, and an up-regulation of HLA-DR, beginning at day 7 after induction. Interferon-gamma (INF-gamma) is known to up-regulate HLA-DR. Therefore we measured INF-gamma levels in the supernatants of TGF-beta3-induced pellets and, indeed, INF-gamma was up-regulated during chondrogenesis in ADSC pellet cultures. However, both undifferentiated and TGF-beta3-induced ADSC also showed expression of immunosuppressive HLA-G and interleukin (IL)-10 up-regulation. CONCLUSIONS: These results suggest that the immunogenicity of adult stem cell-derived tissue should be tested in animal models before clinical trials for allogeneic engineered tissue are considered. FAU - Technau, Antje AU - Technau A AD - Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, Wuerzburg, Germany. FAU - Froelich, Katrin AU - Froelich K FAU - Hagen, Rudolf AU - Hagen R FAU - Kleinsasser, Norbert AU - Kleinsasser N LA - eng PT - Journal Article DEP - 20100826 PL - England TA - Cytotherapy JT - Cytotherapy JID - 100895309 RN - 0 (Biomarkers) RN - 0 (Epitopes) RN - 0 (HLA-DR Antigens) RN - 130068-27-8 (Interleukin-10) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adipose Tissue/*cytology MH - Biomarkers/metabolism MH - Cell Differentiation/*immunology MH - Cells, Cultured MH - Chondrogenesis/*immunology MH - Epitopes/genetics/immunology MH - HLA-DR Antigens/immunology MH - Humans MH - Immune Tolerance/*immunology MH - Immunoassay MH - Interferon-gamma/metabolism MH - Interleukin-10/metabolism MH - Stem Cells/cytology/*immunology MH - Subcellular Fractions/metabolism MH - Up-Regulation EDAT- 2010/08/28 06:00 MHDA- 2011/06/07 06:00 CRDT- 2010/08/28 06:00 PHST- 2010/08/28 06:00 [entrez] PHST- 2010/08/28 06:00 [pubmed] PHST- 2011/06/07 06:00 [medline] AID - S1465-3249(11)70507-2 [pii] AID - 10.3109/14653249.2010.504769 [doi] PST - ppublish SO - Cytotherapy. 2011 Mar;13(3):310-7. doi: 10.3109/14653249.2010.504769. Epub 2010 Aug 26.