Stimulation of immune-competent cells in vitro by human cardiac valve-derived endothelial cells

Hoekstra, Franciska; Knoop, C. J.; Aghai, Zohara; Jutte, N. H. P. M.; Mochtar, B.; Bos, Egbert; Weimar, Willem

doi:10.1016/0003-4975(95)00273-n

Cited by 30 publications

(20 citation statements)

References 11 publications

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“…Although the decellularization procedure has been proved to eliminate ‡ 99% of donor cells, in rare cases, sporadic cells might survive this process; for example, endothelial cells which carry HLA class I and II molecules that are capable of triggering an immune response. [38][39][40] Hawkins et al observed a transient antibody response to HLA-DR in a few patients who had received the Synergraft Ò valve, a decellularized cryopreserved allograft. They hypothesised that these antibodies were directed against cells that are highly immunogenic, such as HLA class II-expressing dendritic cells which may be more resistant to the decellularization process.…”

Section: Discussionmentioning

confidence: 97%

Early Systemic Cellular Immune Response in Children and Young Adults Receiving Decellularized Fresh Allografts for Pulmonary Valve Replacement

Neumann

Sarikouch

Breymann

et al. 2014

Tissue Engineering Part A

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Section: Discussionmentioning

confidence: 97%

Early Systemic Cellular Immune Response in Children and Young Adults Receiving Decellularized Fresh Allografts for Pulmonary Valve Replacement

Neumann

Sarikouch

Breymann

et al. 2014

Tissue Engineering Part A

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“…Based on the findings that the source of allostimulation is the cellular elements9, 10 of the allograft tissue, a number of groups have been investigating decellularization techniques to reduce the immunogenicity of these tissues. To date, the majority of this work has been done in large animal models.…”

Section: Introductionmentioning

confidence: 99%

Comparison of aortic valve allograft decellularization techniques in the rat

Meyer

Chiu

Churchill

et al. 2006

J Biomedical Materials Res

149

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Rodent models have been essential to understanding the immune-mediated failure of aortic valve allografts (AVAs). Decellularization has been proposed to reduce the immunogenicity of AVAs. The objective of this study was to determine the most effective method to decellularize AVAs for use in a rat model. Three different decellularization techniques were compared in Lewis aortic valves. Detergent decellularization involved a series of hypotonic and hypertonic Tris buffers at 4 degrees C for 48 h/buffer containing 0.5% Triton X-100 followed by a 72 h washout in phosphate-buffered saline. Osmotic decellularization was performed in similar manner to the detergent-based technique except without the addition of Triton X-100. Enzymatic decellularization consisted of trypsin/EDTA at 37 degrees C for 48 h. Assessment was performed with light microscopy (H&E, Movat's pentachrome), immunohistochemistry for residual cellular elements, and hydroxyproline assays. Detergent-based methodology effected near-complete decellularization of both the leaflets and aortic wall in addition to preservation of the extracellular matrix (ECM). Osmotic lysis was associated with preservation of ECM and moderate decellularization. Enzymatic decellularization resulted in complete decellularization but extensive degeneration and fragmentation of the ECM. When implanted into the infrarenal aorta of allogeneic rats for 1 week, valves decellularized with detergent-based and osmotic methodology failed to stimulate an allogeneic immune response as evidenced by an absence of T cell infiltrates. Osmotic lysis protocols with low dose detergent appear to be most effective at both removing antigenic cellular elements and preserving ECM.

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“…The question regarding the loss of the endothelium expressing HLA class I and II molecules remains unclear, since con¯icting results have been published [14,15] In this clinical study, we could not assess the presence of viable endothelial cells in the pre-implantation AVCs. However, fresh as well as cryopreserved human aortic valve fragments or valve-derived endothelial cells were able to stimulate allogenic T cells in vitro [16]. Apart from vascular endothelial cells, dendritic cells have been identi®ed in cryopreserved human AVCs, which are capable of presenting foreign HLA class I and II antigens to recipient T cells [17].…”

Section: Discussionmentioning

confidence: 99%

Circulating donor-specific cytotoxic T lymphocytes with high avidity for donor human leukocyte antigens in pediatric and adult cardiac allograft valved conduit recipients✩

Oei

Welters

Knoop

et al. 2000

European Journal of Cardio-Thoracic Surgery

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Objective: Speci®c immunological responses may be involved in the process of cryopreserved allograft valved conduit (AVC) degeneration, which is more frequently seen in young recipients. Rejection of heart and corneal allografts is preceded by an increase in the fraction of cytotoxic T lymphocytes (CTL) with high avidity for donor human leukocyte antigens (HLA) circulating in both peripheral blood and the affected graft. These donor-speci®c high-avidity CTLs are regarded as the destructive cells capable of causing graft damage. To monitor the precursors of these cells (CTLp) in young and adult AVC recipients, in vitro quantitative tests were performed on sequentially taken blood samples to quantitate CTLp frequencies and their avidity for donor antigens. Method: Six children and nine adults who received a cryopreserved AVC in the period between 1994 and 1997 were included in the study. From these patients, two to six blood samples were obtained up to 3 years after valve implantation. The number of circulating CTLp present within the peripheral blood mononuclear cell (PBMC) population was determined by limiting dilution analysis (LDA). The fraction of CTLp with high avidity for donor HLA class I was determined by addition of CD8 monoclonal antibodies (mAb) during the cytotoxic phase of the assay. Third-party stimulator cells were used to verify the donor-speci®city of the response. Results: The number of donor-speci®c CTLp increased signi®cantly in the period 6±12 months after AVC implantation, while third-party-speci®c CTLp frequencies were not affected. Additionally, we found a signi®cant increase of the high-avidity fraction of CTLp directed against donor antigens as early as during the ®rst 6 months after AVC implantation. The fraction of high-avidity CTLp remained signi®cantly higher post-compared with pre-implantation, even after 12 months. We observed no signi®cant difference in the kinetics of CTLp frequencies between pediatric and adult AVC recipients. Conclusion: Implantation of cryopreserved human AVC induces an increase in the total number of circulating CTLp directed against donor HLA class I in both adults and children. The shift towards more destructive high-avidity CTLp in the peripheral blood indicates their potential damaging effect towards the heart valve allograft. q

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Stimulation of immune-competent cells in vitro by human cardiac valve-derived endothelial cells

Cited by 30 publications

References 11 publications

Early Systemic Cellular Immune Response in Children and Young Adults Receiving Decellularized Fresh Allografts for Pulmonary Valve Replacement

Early Systemic Cellular Immune Response in Children and Young Adults Receiving Decellularized Fresh Allografts for Pulmonary Valve Replacement

Comparison of aortic valve allograft decellularization techniques in the rat

Circulating donor-specific cytotoxic T lymphocytes with high avidity for donor human leukocyte antigens in pediatric and adult cardiac allograft valved conduit recipients✩

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