Immune Response to Xenogeneic Matrix Grafts Used in Pediatric Surgery

Meyer, T.; Meyer, Bettina; Schwarz, Karin; Höcht, B.

doi:10.1055/s-2007-989306

Cited by 12 publications

(24 citation statements)

References 19 publications

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“…In experimental animal models production of anti-non gal antibodies was also reflected in the reported anti-TH2 immune response that facilitates antibody response and is observed in recipients of xenogeneic ECM. [8][9][10] Production of both antiGal and anti-non gal antibodies cannot be prevented by immunosuppression protocols potent enough to prevent allograft rejection. 11 This review describes the characteristics of these antibodies primarily in humans and monkeys.…”

Section: Introductionmentioning

confidence: 99%

Avoiding Detrimental Human Immune Response Against Mammalian Extracellular Matrix Implants

Galili

2015

Tissue Engineering Part B: Reviews

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This review describes the antibodies formed against mammalian extracellular matrix (ECM) implants in humans and proposes methods for avoiding the detrimental effects of these antibodies. There are two types of antibodies against ECM implants: (i) The natural anti-Gal antibody constituting ∼1% of immunoglobulins in humans. This antibody binds to a carbohydrate antigen called the α-gal epitope with the structure Galα1-3Galβ1-4GlcNAc-R. The α-gal epitope is abundant in nonprimate mammals, including on ECM proteins and proteoglycans. Moreover, anti-Gal antibody titers increase within 2-4 weeks by 10- to 100-folds in human recipients of mammalian implants or xenografts expressing α-gal epitopes. (ii) Anti-non gal antibodies formed against ECM peptide sequences differing from those in homologous proteins in humans. Most homologous proteins in mammals contain immunogenic peptides that elicit anti-non gal antibody production when introduced into humans. Formation of anti-non gal antibodies is much slower than that of elicited anti-Gal antibodies. Both anti-Gal and anti-non gal antibodies are detrimental to ECM implant regeneration in humans by binding to the ECM and directing extensive macrophage-mediated degradation of the implant. In addition, antibodies binding to ECM proteins/proteoglycans may hinder stem cells interaction with the ECM, which is required for directing stem cell differentiation. The anti-Gal immunological barrier can be avoided by using mammalian ECM implants lacking α-gal epitopes. Such implants can be engineered by enzymatic destruction of α-gal epitopes with recombinant α-galactosidase. Alternatively, implants may be obtained from α1,3galactosyltransferase knockout donor species that lack α-gal epitopes. Since postimplantation production of anti-non gal antibodies is a slow process, the detrimental effects of these antibodies may be avoided by accelerating stem cells recruitment into implants, thus accelerating the regeneration process. Acceleration of stem cell recruitment may be achieved by introducing α-gal nanoparticles into the implant. α-Gal nanoparticles present multiple α-gal epitopes, which bind anti-Gal and induce recruitment of macrophages by generating complement chemotactic factors. Fc/Fcγ receptor interaction between anti-Gal coating α-gal nanoparticles and recruited macrophages activates the macrophages to secrete "pro-healing" cytokines/growth factors that recruit stem cells. These recruited cells are instructed by the implanted ECM to regenerate the implant before anti-non gal antibodies can reach detrimental titers.

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Section: Introductionmentioning

confidence: 99%

Avoiding Detrimental Human Immune Response Against Mammalian Extracellular Matrix Implants

Galili

2015

Tissue Engineering Part B: Reviews

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“…Extrazelluläre Matrixproteine werden heute auf dem gesamten Gebiet der Chirurgie als sogenannte Bioscaffolds eingesetzt, da sie in Abhängigkeit von der Implantationsdauer langsam durch körper-eigenes Gewebe ersetzt werden [18,19]. Unklar ist in diesem Zusammenhang jedoch, warum diese implantierten xenogenen Materialien keine Abstoßungsre- …”

Section: Diskussionunclassified

“…Hierbei produzieren T H 1-Lymphozyten Interleukin-(IL)2, Interferon (IFN) und Tumornekrosefaktoren (TNF), wodurch sie wiederum Makrophagen aktivieren und die Differenzierung von CD81-positiven Zellen in zytotoxische Phäno-typen triggern [2]. Verschiedene Arbeitsgruppen konnten zeigen, dass die Aktivierung dieser immunologischen Kaskade sowohl bei der allogenen als auch xenogenen Transplantatabstoßung vorkommt [1,2,10,19]. T H 2-Lymphozyten hingegen produzieren IL-4, IL-5, IL-6 und IL-10.…”

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“…Die Aktivierung des T H 2-Pathway ist somit mit einer Transplantatakzeptanz verbunden [2,18]. Unsere Ergebnisse lassen in Anbetracht der gegenwärtigen Literatur [1,10,18,19] den Schluss zu, dass der T H 2-Pathway ebenfalls eine Rolle bei der Akzeptanz von xenogenen avaskulären Transplantaten, wie z. B. Lyoplant (PAULProcedure), zu spielen scheint.…”

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“…Somit konnten die guten Ergebnisse aus dem Kleintiermodell auch im Großtiermodell reproduziert werden. Unsere Ergebnisse der Dickenmessungen des implantierten Materials untermauern zudem die Hypothese, dass im Gegensatz zu resorbierbaren Materialien die biokompatiblen Materialien nicht einem konstanten Abbauprozess unterliegen, sondern funktionell durch kör-pereigenes Gewebe ersetzt werden [1,10,19]. Hier müssen jedoch noch weitere analytische Untersuchungen folgen.…”

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PAUL-Procedure

Meyer

Seifert

Meyer

et al. 2009

Chirurg

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Treatment of small congenital abdominal wall defects (e.g. omphalocele and gastroschisis) can be performed by direct closure. In large defects non-resorbable artificial materials (e.g. Gore-Tex) are necessary to close the fascia. The aim of this study was to find out whether a new procedure, the PAUL pocedure, might be suitable for the treatment of large abdominal wall defects. A full thickness abdominal wall defect was created in young Wistar Rats. These defects were then closed by implantation of a 1x2 cm sized piece of PTFE (Dual-Mesh), a polypropylene mesh (Prolene(R)) or by using the PAUL procedure. Over a period of 6 weeks no wound infections or hernias were monitored. In contrast to PTFE the PAUL procedure showed only minimal adhesion to the intestine and a high stability of the implanted material. A xenogenic extracellular matrix, such as that used in the PAUL procedure, may induce an immune response, which is comparable with a remodeling reaction rather than rejection. Based on these good results a large animal model study (Goettinger mini-piglets) was performed. No wound infections or hernias could be observed throughout the experiment. Control laparoscopy after 3, 6, 9, and 12 months showed only minimal adhesion to the intestine. Our results indicate that the PAUL procedure can be used easily and successfully for the therapy of congenital abdominal wall defects.

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Limitations of recellularized biological scaffolds for human transplantation

Bilodeau

Goltsis

Rogers

et al. 2020

J Tissue Eng Regen Med

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A shortage of donor organs for transplantation and the dependence of the recipients on immunosuppressive therapy have motivated researchers to consider alternative regenerative approaches. The answer may reside in acellular scaffolds generated from cadaveric human and animal tissues. Acellular scaffolds are expected to preserve the architectural and mechanical properties of the original organ, permitting cell attachment, growth, and differentiation. Although theoretically, the use of acellular scaffolds for transplantation should pose no threat to the recipient's immune system, experimental data have revealed significant immune responses to allogeneic and xenogeneic transplanted scaffolds. Herein, we review the various factors of the scaffold that could trigger an inflammatory and/or immune response, thereby compromising its use for human transplant therapy. In addition, we provide an overview of the major cell types that have been considered for recellularization of the scaffold and their potential contribution to triggering an immune response.

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Immune Response to Xenogeneic Matrix Grafts Used in Pediatric Surgery

Abstract: A xenogeneic extracellular matrix, such as Lyoplant, may induce an immune response which is predominantly TH2-like and comparable with a remodelling reaction rather than rejection.

Cited by 12 publications

References 19 publications

Avoiding Detrimental Human Immune Response Against Mammalian Extracellular Matrix Implants

Avoiding Detrimental Human Immune Response Against Mammalian Extracellular Matrix Implants

PAUL-Procedure

Limitations of recellularized biological scaffolds for human transplantation

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