Anna C Biermann1,2,3, Julia Marzi3,4, Eva Brauchle3,4, Maria Schneider5,6, Angela Kornberger7, Sherif Abdelaziz1, Julian L Wichmann8, Christophe T Arendt8, Eike Nagel8, Kelvin G M Brockbank9,10, Martina Seifert5,6, Katja Schenke-Layland3,4,11, Ulrich A Stock1,2,12,13. 1. Department of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany. 2. Department of Cardiothoracic Surgery, Royal Brompton and Harefield Foundation Trust, Harefield, UK. 3. Department of Women's Health, Research Institute for Women's Health, Eberhard-Karls-University, Tuebingen, Germany. 4. Department of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), Stuttgart, Germany. 5. Institue of Medical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. 6. Berlin-Brandenburg Center of Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. 7. Department of Cardiothoracic and Vascular Surgery, Johannes Gutenberg-University, Mainz, Germany. 8. Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany. 9. Tissue Testing Technologies LLC, North Charleston, SC, USA. 10. Department of Bioengineering, Clemson University, North Charleston, SC, USA. 11. Department of Medicine / Cardiology, Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. 12. Faculty of Medicine, Imperial College London, London, UK. 13. Magdi Yacoub Institute, Heart Science Centre, Harefield, UK.
Abstract
OBJECTIVES: Allogeneic frozen cryopreserved heart valves (allografts or homografts) are commonly used in clinical practice. A major obstacle for their application is the limited availability in particular for paediatrics. Allogeneic large animal studies revealed that alternative ice-free cryopreservation (IFC) results in better matrix preservation and reduced immunogenicity. The objective of this study was to evaluate xenogeneic (porcine) compared with allogeneic (ovine) IFC heart valves in a large animal study. METHODS: IFC xenografts and allografts were transplanted in 12 juvenile merino sheep for 1-12 weeks. Immunohistochemistry, ex vivo computed tomography scans and transforming growth factor-β release profiles were analysed to evaluate postimplantation immunopathology. In addition, near-infrared multiphoton imaging and Raman spectroscopy were employed to evaluate matrix integrity of the leaflets. RESULTS: Acellular leaflets were observed in both groups 1 week after implantation. Allogeneic leaflets remained acellular throughout the entire study. In contrast, xenogeneic valves were infiltrated with abundant T-cells and severely thickened over time. No collagen or elastin changes could be detected in either group using multiphoton imaging. Raman spectroscopy with principal component analysis focusing on matrix-specific peaks confirmed no significant differences for explanted allografts. However, xenografts demonstrated clear matrix changes, enabling detection of distinct inflammatory-driven changes but without variations in the level of transforming growth factor-β. CONCLUSIONS: Despite short-term success, mid-term failure of xenogeneic IFC grafts due to a T-cell-mediated extracellular matrix-triggered immune response was shown.
OBJECTIVES: Allogeneic frozen cryopreserved heart valves (allografts or homografts) are commonly used in clinical practice. A major obstacle for their application is the limited availability in particular for paediatrics. Allogeneic large animal studies revealed that alternative ice-free cryopreservation (IFC) results in better matrix preservation and reduced immunogenicity. The objective of this study was to evaluate xenogeneic (porcine) compared with allogeneic (ovine) IFC heart valves in a large animal study. METHODS: IFC xenografts and allografts were transplanted in 12 juvenile merino sheep for 1-12 weeks. Immunohistochemistry, ex vivo computed tomography scans and transforming growth factor-β release profiles were analysed to evaluate postimplantation immunopathology. In addition, near-infrared multiphoton imaging and Raman spectroscopy were employed to evaluate matrix integrity of the leaflets. RESULTS: Acellular leaflets were observed in both groups 1 week after implantation. Allogeneic leaflets remained acellular throughout the entire study. In contrast, xenogeneic valves were infiltrated with abundant T-cells and severely thickened over time. No collagen or elastin changes could be detected in either group using multiphoton imaging. Raman spectroscopy with principal component analysis focusing on matrix-specific peaks confirmed no significant differences for explanted allografts. However, xenografts demonstrated clear matrix changes, enabling detection of distinct inflammatory-driven changes but without variations in the level of transforming growth factor-β. CONCLUSIONS: Despite short-term success, mid-term failure of xenogeneic IFC grafts due to a T-cell-mediated extracellular matrix-triggered immune response was shown.
Authors: Milan Lisy; Juliane Pennecke; Kelvin G M Brockbank; Olaf Fritze; Martina Schleicher; Katja Schenke-Layland; Renate Kaulitz; Iris Riemann; Corinna N Weber; Josephine Braun; Kerstin E Mueller; Falko Fend; Torsten Scheunert; Achim D Gruber; Johannes M Albes; Agnes J Huber; Ulrich A Stock Journal: Biomaterials Date: 2010-07 Impact factor: 12.479
Authors: Anneke Neumann; Samir Sarikouch; Thomas Breymann; Serghei Cebotari; Dietmar Boethig; Alexander Horke; Philipp Beerbaum; Mechthild Westhoff-Bleck; Harald Bertram; Masamichi Ono; Igor Tudorache; Axel Haverich; Gernot Beutel Journal: Tissue Eng Part A Date: 2014-01-24 Impact factor: 3.845
Authors: Youjin Lee; Amit Awasthi; Nir Yosef; Francisco J Quintana; Sheng Xiao; Anneli Peters; Chuan Wu; Markus Kleinewietfeld; Sharon Kunder; David A Hafler; Raymond A Sobel; Aviv Regev; Vijay K Kuchroo Journal: Nat Immunol Date: 2012-09-09 Impact factor: 25.606
Authors: Julia Marzi; Emma C Munnig Schmidt; Eva M Brauchle; Tamar B Wissing; Hannah Bauer; Aurelie Serrero; Serge H M Söntjens; Anton W Bosman; Martijn A J Cox; Anthal I P M Smits; Katja Schenke-Layland Journal: Front Cardiovasc Med Date: 2022-05-17