Impact of T-cell-mediated immune response on xenogeneic heart valve transplantation: short-term success and mid-term failure

Biermann, Anna; Marzi, Julia; Brauchle, Eva; Schneider, Maria; Kornberger, Angela; Abdel‐Aziz, Salah A.; Wichmann, Julian L.; Arendt, Christophe; Nagel, Eike; Brockbank, K. G. M.; Seifert, Martina; Schenke‐Layland, Katja; Stock, Ulrich A.

doi:10.1093/ejcts/ezx396

Cited by 9 publications

(11 citation statements)

References 29 publications

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“…Ice-free cryopreserved porcine pulmonary valves tested by Biermann and colleagues exhibited intensive calcifications and a strong T cell-mediated immune reaction after 3 months in vivo. 32 On the contrary, other in vivo studies of decellularized porcine heart valves in sheep were reporting very good preclinical results. [33][34][35][36] Goldstein and colleagues reported successful implantation and function of SynerGraft valves made from decellularized porcine aortic valve tissue for up to 336 days in the sheep model.…”

Section: Discussionmentioning

confidence: 99%

Decellularization combined with enzymatic removal of N‐linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model

Ramm

Goecke

Theodoridis

et al. 2019

Xenotransplantation

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Background Limited availability of decellularized allogeneic heart valve substitutes restricts the clinical application thereof. Decellularized xenogeneic valves might constitute an attractive alternative; however, increased immunological hurdles have to be overcome. This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N‐glycan and DNA removal. Methods dpPHV generated by nine different decelluarization methods were characterized in respect of DNA, hydroxyproline, GAGs, and SDS content. Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host. Allogenic doPHV implantations (n = 3) from a previous study served as control. Results Among the decellularization procedures, Triton X‐100 & SDS as well as trypsin & Triton X‐100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact. In vivo, the functional performance of dpPHV was comparable to that of allogeneic controls. Removal of N‐linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X‐100 & SDS dpPHV, whereas this treatment of trypsin & Triton X‐100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants. Conclusion Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.

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Section: Discussionmentioning

confidence: 99%

Decellularization combined with enzymatic removal of N‐linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model

Ramm

Goecke

Theodoridis

et al. 2019

Xenotransplantation

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“…We found that sEV derived from two species could significantly promote the migration of host cells compared with the blank group at early implantation stage, which might lead to elevated neoadipose tissue formation in silicone tube at 8 weeks post implantation. Up to now, immune response induced by xenografts have been reported mainly at the organ 64 and cellular 65 levels, but no study focuses on xenogeneic extracellular vesicle. In this study, although host cells recruitment caused by implantation were promoted in sEV-AT groups, there was no significant difference between allogeneic and xenogeneic sEV-AT groups.…”

Section: Discussionmentioning

confidence: 99%

<p>Comparison of the Therapeutic Effect of Allogeneic and Xenogeneic Small Extracellular Vesicles in Soft Tissue Repair</p>

Dong

Wu²,

Zhang

et al. 2020

IJN

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Small extracellular vesicles (sEV) are a heterogeneous group of vesicles that consist of proteins, lipids and miRNA molecules derived from the cell of origin. Although xenogeneic sEV have been applied for soft tissue regeneration successfully, the regeneration effect of allogeneic and xenogeneic sEV has not been compared systematically. Methods: Our previous study has shown that sEV derived from rat adipose tissue successfully induced neoadipose regeneration. In this study, sEV were isolated from rat adipose tissue (r-sEV-AT) and porcine adipose tissue (p-sEV-AT), the morphology, size distribution and marker proteins expression of r-sEV-AT and p-sEV-AT were characterized. Besides, the sEV/AT ratio was evaluated and compared between r-sEV-AT and p-sEV-AT. Rat adipose-derived stromal/ stem cells (rASCs) and rat aorta endothelial cells (rECs) were adopted to test the cellular response to allogeneic and xenogeneic sEV-AT. The effects of allogeneic and xenogeneic sEV-AT on host cells migration and neoadipose formation were evaluated in a subcutaneous customdesigned model. A full-thickness skin wound healing model was used to further compare the ability of allogeneic and xenogeneic sEV-AT in inducing complex soft tissue regeneration. Results: p-sEV-AT showed similar morphology and size distribution to r-sEV-AT. Marker proteins of sEV were detected in both r-sEV-AT and p-sEV-AT. The sEV/AT ratio of porcine was slightly higher than that of rat. The effects of r-sEV-AT and p-sEV-AT on the differentiation of rASCs and rECs showed no significant difference. When allogeneic and xenogeneic sEV-AT were subcutaneously implanted into the back of SD rats, the host cells chemotactic infiltration was observed in 1 week and neoadipose tissue formation was induced in 8 weeks; no significant difference was observed between allogeneic and xenogeneic sEV-AT. For complex soft tissue regeneration, both allogeneic and xenogeneic sEV-AT significantly promoted wound re-epithelialization, granulation tissue formation and hair follicle regeneration and then accelerated skin wound healing. Conclusion: Our results demonstrated that sEV derived from the same tissues of different species might be loaded with similar therapeutic substance benefitting tissue repair and regeneration, and paved the way for future research aimed at xenogeneic sEV application.

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“…In contrast to quantitative information, these methods are limited in their capability to address qualitative changes in structural composition of collagen fibers. Here, Raman spectroscopy has already been shown to be sensitive to changes in collagen fibers upon aging, tissue degradation or foreign body response ( 52 – 54 ) and was applied in this study to determine collagen maturation at different explantation timepoints and explant regions. Comparison between 6 and 12-month explants showed similar results in molecular changes for collagens between the polymer fibers and in the lumen.…”

Section: Discussionmentioning

confidence: 99%

Marker-Independent Monitoring of in vitro and in vivo Degradation of Supramolecular Polymers Applied in Cardiovascular in situ Tissue Engineering

Marzi

Schmidt

Brauchle

et al. 2022

Front. Cardiovasc. Med.

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The equilibrium between scaffold degradation and neotissue formation, is highly essential for in situ tissue engineering. Herein, biodegradable grafts function as temporal roadmap to guide regeneration. The ability to monitor and understand the dynamics of degradation and tissue deposition in in situ cardiovascular graft materials is therefore of great value to accelerate the implementation of safe and sustainable tissue-engineered vascular grafts (TEVGs) as a substitute for conventional prosthetic grafts. In this study, we investigated the potential of Raman microspectroscopy and Raman imaging to monitor degradation kinetics of supramolecular polymers, which are employed as degradable scaffolds in in situ tissue engineering. Raman imaging was applied on in vitro degraded polymers, investigating two different polymer materials, subjected to oxidative and enzymatically-induced degradation. Furthermore, the method was transferred to analyze in vivo degradation of tissue-engineered carotid grafts after 6 and 12 months in a sheep model. Multivariate data analysis allowed to trace degradation and to compare the data from in vitro and in vivo degradation, indicating similar molecular observations in spectral signatures between implants and oxidative in vitro degradation. In vivo degradation appeared to be dominated by oxidative pathways. Furthermore, information on collagen deposition and composition could simultaneously be obtained from the same image scans. Our results demonstrate the sensitivity of Raman microspectroscopy to determine degradation stages and the assigned molecular changes non-destructively, encouraging future exploration of this techniques for time-resolved quality assessment of in situ tissue engineering processes.

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Impact of T-cell-mediated immune response on xenogeneic heart valve transplantation: short-term success and mid-term failure

Abstract: Despite short-term success, mid-term failure of xenogeneic IFC grafts due to a T-cell-mediated extracellular matrix-triggered immune response was shown.

Cited by 9 publications

References 29 publications

Decellularization combined with enzymatic removal of N‐linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model

Decellularization combined with enzymatic removal of N‐linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model

<p>Comparison of the Therapeutic Effect of Allogeneic and Xenogeneic Small Extracellular Vesicles in Soft Tissue Repair</p>

Marker-Independent Monitoring of in vitro and in vivo Degradation of Supramolecular Polymers Applied in Cardiovascular in situ Tissue Engineering

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