Xellfree®
Zellfreie Allografts
Allografts, wie z.B. menschliche Herzklappen, sind anatomisch perfekt an ihre Aufgabe angepasst. Daher zeigen Allografts, früher auch als "Homografts" bekannt, grundsätzlich gute Langzeitergebnisse. Der Nachteil von konventionellen Allografts ist, dass sie vom Immunsystem erkannt werden können. Dies kann zu einem Funktionsverlust des Allografts führen und eine Reintervention oder Reoperation erfordern.
Bei der "Dezellularisierung" werden die Zellen aus der Gewebespende entfernt. Es bleibt nur das zellfreie Bindegewebe übrig. Das nun zellfreie Allograft behält seine ursprüngliche Form und volle Funktionsfähigkeit. Während Zellmarker die Individualität jedes einzelnen Menschen bestimmen, ist das Bindegewebe nicht immunologisch individualisiert. Zellfreie Allografts werden daher seltener als konventionelle (kryokonservierte) Allografts vom Empfänger abgestoßen.
Xellfree®Process
Discover more in this slideshow about the Xellfree®-process.
Tissue donation
Corlife cooperates with recognized organizations that carefully select suitable tissue donations. The criteria are described in the European Directive 2004/23, which has been amended several times. The selection includes a detailed anamnesis of the donor, serological examinations, an external and internal body examination, as well as morphological and microbiological examinations of the tissue donation.
Processing
The allografts are processed in the highest clean room class (Class A). Care of the employees and very high hygienic and technical standards prevent contamination during processing. We regularly sample the contact surfaces in order to detect microbial contamination at an early stage and push it back.
Cell-free
Before we deliver a cell-free allograft, tissue samples are histologically examined by an independent specialist in pathology. No intact cell nuclei must be detectable in the cell-free tissue sample.
Cell-free
Double-stranded DNA (dsDNA) is a component of the cell nuclei and thus a surrogate parameter for cell density. The dsDNA mass in the arterial wall varies greatly from tissue donation to tissue donation (150-4,250 ng/mg, n=40). In the literature, "cell-free" is defined as ≤50 ng dsDNA per mg tissue (Crapo et al., Biomaterials. 2011 Apr; 32(12):3233-43). Xellfree®technology is more sophisticated: after decellularization, only ≤25 ng dsDNA per mg of tissue may be detectable. The residual content in >90% of all cell-free allografts (n=641) is even only ≤10 ng/mg.
Intact extracellular matrix
Each individual allograft is histologically examined by an independent specialist in pathology. The extracellular matrix must have a fibrous structure that suggests a healthy donor. Allografts with e.g. myxoid fiber structure are rejected.
Germ-free
Every cell-free allograft is processed aseptically. Terminal sterilization would denature the allograft and destroy its regenerative potential. At the end of processing, samples are taken from each allograft, incubated for two weeks in culture media under optimal conditions and then tested for sterility. We only give aseptic, cell-free allografts.
Left: no findings, right: contaminated
Without antibiotics
Conventional allografts (homografts) are treated with a high-dose antibiotic cocktail and then frozen. The Xellfree®process does not require antibiotics.
Chilled
Cell-free allografts are not frozen at any time, but stored and transported in a cool place. Gentle processing avoids freezing damage to the cell-free tissue.
Clinical experience
Cell-free human heart valves are always implanted with a more or less long piece of the adjacent vessel (ascending aorta, truncus pulmonalis) that carries the valve.
No cellular immunogenicity
Neumann et al (2014) examined the peripheral blood of 47 patients who received cell-free pulmonary valves over a period of three years. No elevated levels of T cells (CD3+, CD8+), B cells (CD19+), killer cells (CD16+/CD56+) or T helper cells (CD4+) could be detected. The cell-free pulmonary valves were immunologically silent.
“Early Systemic Cellular Immune Response in Children and Young Adults Receiving Decellularized Fresh Allografts for Pulmonary Valve Replacement”
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Cellular Restoration
Sarikouch et al (2019) investigated the postoperative immigration of cells into decellularized allograft. The relative histologic score (100% corresponds to complete cellular restoration) in samples that did not exhibit endocarditis (n=6) was 76±4%. Intracellular procollagen type 1 was found in the mesenchymal recipient cells. In endocarditis samples (n=5), the histological score was significantly lower at 48±7%, associated with leukocyte infiltration and matrix degradation. A cell-free pulmonary valve showed an immune system related graft failure. Allografts sampled in the first 12 months post-op showed a thin colonization of the media. In terms of the degree of restoration, no difference was found between a cell-free aortic or pulmonary heart valve.
“Early Insight Into In Vivo Recellularization of Cell-Free Allogenic Heart Valves”
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Cell-free pulmonary valve
Boethig et al (2019) describes a total of 235 patients, 121 of whom were prospectively included in the multicenter ESPOIR observational study (2014-2016). The study group was compared with similar cohorts (propensity-matched) who received a conventional allograft or bioprosthesis. Decellularized allografts showed fewer adverse events than the control groups during the observation period.
“A European study on decellularized homografts for pulmonary valve replacement: initial results from the prospective ESPOIR Trial and ESPOIR Registry data”
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Cell-free aortic valve
Horke et al (2020) describes a total of 223 patients, 144 of whom were prospectively enrolled in the multicenter ARISE observational study (2015-2018). The study group was compared with similar cohorts (propensity-matched) who received conventional heart valve prostheses or underwent "Ross surgery". Decellularized allografts showed fewer adverse events than the control groups during the observation period. Cell-free human aortic valves with a long vascular component are a therapeutic alternative for valve replacement in combination with the replacement of a dilated ascending aorta (Tudorache 2016).
“Early results form a prospective, single-arm European trial on decellularized allografts for aortic valve replacement: the ARISE study and ARISE Registry data”
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Cell-free aortic valve for children
A subgroup analysis of young patients (10±5 years) describes the cell-free aortic valve as a beneficial therapeutic alternative to conventional prostheses (Horke et al. (2020-2).
"Paediatric aortic valve replacement using decellularized allografts
“Paediatric aortic valve replacement using decellularized allografts”
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Replacing the aortic and pulmonary valve
Cell-free human heart valves are also suitable for double valve replacement. Since the cell-free design leads to less rejection, matching heart valves from different donors can be implanted (Bobylev 2019).
“Double semilunar valve replacement in complex congenital heart disease using decellularized homografts.”
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