PMID- 28130912 OWN - NLM STAT- MEDLINE DCOM- 20191009 LR - 20191010 IS - 1932-7005 (Electronic) IS - 1932-6254 (Linking) VI - 12 IP - 2 DP - 2018 Feb TI - Effects on human heart valve immunogenicity in vitro by high concentration cryoprotectant treatment. PG - e1046-e1055 LID - 10.1002/term.2426 [doi] AB - It has been shown previously that cryopreservation, using an ice-free cryopreservation method with the cryoprotectant formulation VS83, beneficially modulated immune reactions in vivo and in vitro when compared with conventionally frozen tissues. In this study, we assessed the impact of a VS83 post-treatment of previously conventionally frozen human tissue on responses of human immune cells in vitro. Tissue punches of treated and non-treated (control) aortic heart valve tissue (leaflets and associated aortic root) were co-cultured for 7 days with peripheral blood mononuclear cells or enriched CD14(+) monocytes. Effects on cellular activation markers, cytokine secretion and immune cell proliferation were analysed by flow cytometry. Flow cytometry studies showed that VS83 treatment of aortic root tissue promoted activation and differentiation of CD14(+) monocytes, inducing both up-regulation of CD16 and down-regulation of CD14. Significantly enhanced expression levels for the C-C chemokine receptor (CCR)7 and the human leukocyte antigen (HLA)-DR on monocytes co-cultured with VS83-treated aortic root tissue were measured, while the interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 release was suppressed. However, the levels of interferon (IFN)gamma and tumour necrosis factor (TNF)alpha remained undetectable, indicating that complete activation into pro-inflammatory macrophages did not occur. Similar, but non-significant, changes occurred with VS83-treated leaflets. Additionally, in co-cultures with T cells, proliferation and cytokine secretion responses were minimal. In conclusion, post-treatment of conventionally cryopreserved human heart valve tissue with the VS83 formulation induces changes in the activation and differentiation characteristics of human monocytes, and thereby may influence long-term performance following implantation. Copyright (c) 2017 John Wiley & Sons, Ltd. CI - Copyright (c) 2017 John Wiley & Sons, Ltd. FAU - Hogerle, Benjamin A AU - Hogerle BA AD - Department for Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. FAU - Schneider, Maria AU - Schneider M AD - Institute of Medical Immunology, Charite Universitatsmedizin Berlin, Germany. AD - Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charite Universitatsmedizin, Berlin, Germany. FAU - Sudrow, Katrin AU - Sudrow K AD - Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charite Universitatsmedizin, Berlin, Germany. FAU - Souidi, Naima AU - Souidi N AD - Institute of Medical Immunology, Charite Universitatsmedizin Berlin, Germany. AD - Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charite Universitatsmedizin, Berlin, Germany. FAU - Stolk, Meaghan AU - Stolk M AD - Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charite Universitatsmedizin, Berlin, Germany. FAU - Werner, Isabella AU - Werner I AD - Department for Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. FAU - Biermann, Anna AU - Biermann A AD - Department for Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. FAU - Brockbank, Kelvin G M AU - Brockbank KGM AD - Tissue Testing Technologies LLC, North Charleston, SC, USA. AD - Department of Bioengineering, Clemson University, SC, USA. AD - Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA. FAU - Stock, Ulrich A AU - Stock UA AD - Department for Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. FAU - Seifert, Martina AU - Seifert M AUID- ORCID: 0000-0002-6372-9769 AD - Institute of Medical Immunology, Charite Universitatsmedizin Berlin, Germany. AD - Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charite Universitatsmedizin, Berlin, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170607 PL - England TA - J Tissue Eng Regen Med JT - Journal of tissue engineering and regenerative medicine JID - 101308490 RN - 0 (Cryoprotective Agents) RN - 0 (Cytokines) RN - 0 (Quinazolines) RN - 0 (Thiones) RN - 0 (vasastrol VS-83) SB - IM MH - Cell Differentiation/drug effects MH - Cell Proliferation/drug effects MH - Cryopreservation MH - Cryoprotective Agents/*pharmacology MH - Cytokines/metabolism MH - Freezing MH - Heart Valves/drug effects/*immunology MH - Humans MH - Macrophages/drug effects/metabolism MH - Monocytes/cytology/drug effects MH - Quinazolines/pharmacology MH - Thiones/pharmacology OTO - NOTNLM OT - cryopreservation OT - heart valve OT - human aorta OT - immunogenicity EDAT- 2017/01/29 06:00 MHDA- 2019/10/11 06:00 CRDT- 2017/01/29 06:00 PHST- 2016/06/24 00:00 [received] PHST- 2017/01/16 00:00 [revised] PHST- 2017/01/20 00:00 [accepted] PHST- 2017/01/29 06:00 [pubmed] PHST- 2019/10/11 06:00 [medline] PHST- 2017/01/29 06:00 [entrez] AID - 10.1002/term.2426 [doi] PST - ppublish SO - J Tissue Eng Regen Med. 2018 Feb;12(2):e1046-e1055. doi: 10.1002/term.2426. Epub 2017 Jun 7.