The Immune Response to Crosslinked Tissue is Reduced in Decellularized Xenogeneic and Absent in Decellularized Allogeneic Heart Valves

Böer, Ulrike; Schridde, Ariane; Anssar, Marcel; Klingenberg, Melanie; Sarikouch, Samir; Dellmann, Ansgar; Harringer, Wolfgang; Haverich, Axel; Wilhelmi, Mathias

doi:10.5301/ijao.5000395

Cited by 25 publications

(35 citation statements)

References 36 publications

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“…Indeed, stenosis rates observed in Scid and wild‐type mice, following TEVGs implant, were similar . As also demonstrated for heart valve implants in humans, the humoral response to the implant was reduced in decellularized xenogeneic (porcine) valves and almost absent in decellularized allogeneic valves, in comparison with the response to glutaraldehyde‐fixed, nondecellularized equine‐derived conduits .…”

Section: Effects Of Structure and Composition Of Implanted Materials supporting

confidence: 70%

Inflammation in tissue engineering: The Janus between engraftment and rejection

et al. 2015

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Tissue engineering (TE) for tissue and organ regeneration or replacement is generally performed with scaffold implants, which provide structural and molecular support to in vitro seeded or in vivo recruited cells. TE implants elicit the host immune response, often resulting in engraftment impediment or rejection. Besides this negative effect, however, the immune system components also yield a positive influence on stem cell recruitment and differentiation, allowing tissue regeneration and healing. Thus, a balanced cooperation between proinflammatory and proresolution players of the immune response is an essential element of implant success. In this context, macrophage plasticity plays a fundamental role. Therefore modulating the immune response, instead of immune suppressing the host, might be the best way to successfully implant TE tissues or organs. In particular, it is becoming evident that the scaffold, immune, and stem cells are linked by a three-way interaction, and many efforts are being made for scaffold-appropriate design and functionalization in order to drive the inflammation process toward regeneration, vascularization, and implant success. This review discusses current and potential strategies for inflammation modulation to aid engraftment and regeneration, supporting the concept that quality, and not quantity, of inflammation might influence implant success.Keywords: Implant r Macrophage r Scaffold r Stem cell r Tissue engineering IntroductionTissue engineering and regenerative medicine (TERM) applications intend to improve or replace compromised biological functions by stimulating the intrinsic regenerative capacity of the body or even by replacing damaged tissues and organs. To provide the structure and attachment surface to drive tissue regeneration, Correspondence: Prof. Laura Teodori e-mail: laura.teodori@enea.it scaffolds of synthetic, or natural origin, which may or may not be seeded with stem cells, are constructed and implanted into the human body to foster regeneration. Scaffolds are particularly important for the replacement of a variety of tissues such as skin, bone, and muscle tissue (e.g. maxillofacial reconstructions, heart valves, and vessels) [1]. Depending on the type of tissue to be * These authors contributed equally to this work.C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 3222-3236 HIGHLIGHTS 3223replaced, different types of scaffolds are suitable to support regeneration and engraftment. This review provides a general view on the different biomaterials/scaffold types and properties; however the available literature on the matter extensively reports the most frequently used types of scaffolds and their application [2,3]. Although TERM research greatly advanced in recent years, one major challenge is the immune response elicited by the implant, which often leads to a precocious reabsorption, to fibrosis of the implant, and/or to implant rejection, leading to eventual failure of the intervention [4]. To ensure the success of t...

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Section: Effects Of Structure and Composition Of Implanted Materials supporting

confidence: 70%

Inflammation in tissue engineering: The Janus between engraftment and rejection

et al. 2015

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“…Of several proposed procedures, bile acids and DOC in particular, alone or in combination with other surfactants, have been adopted in the preparation of heart valve substitutes currently under consideration for clinical use [1, 13, 16, 33]. The ability to remove the antigenic determinants of the cell debris holds great promise, since this would eliminate donor-specific immunoresponse in the case of homografts and also avoid the wide use of glutaraldehyde for prevention of rejection-related reactions of xenografts.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to uneventful follow-up, poor effective viability and activity of engrafting cell elements and limited freedom from graft dysfunction have been reported [1, 16, 17]. …”

Section: Introductionmentioning

confidence: 99%

Natural Scaffolds for Regenerative Medicine: Direct Determination of Detergents Entrapped in Decellularized Heart Valves

Dettin

Zamuner

Naso

et al. 2017

BioMed Research International

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The increasing urgency for replacement of pathological heart valves is a major stimulus for research on alternatives to glutaraldehyde-treated grafts. New xenogeneic acellular heart valve substitutes that can be repopulated by host cells are currently under investigation. Anionic surfactants, including bile acids, have been widely used to eliminate the resident cell components chiefly responsible for the immunogenicity of the tissue, even if detergent toxicity might present limitations to the survival and/or functional expression of the repopulating cells. To date, the determination of residual detergent has been carried out almost exclusively on the washings following cell removal procedures. Here, a novel HPLC-based procedure is proposed for the direct quantification of detergent (cholate, deoxycholate, and taurodeoxycholate) residues entrapped in the scaffold of decellularized porcine aortic and pulmonary valves. The method was demonstrated to be sensitive, reproducible, and extendable to different types of detergent. This assessment also revealed that cell-depleted heart valve scaffolds prepared according to procedures currently considered for clinical use might contain significant amount of surfactant.

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“…In the current study, the immunogenicity of ga-fixed porcine heart valves was determined by measuring IgG-class and IgM-class antibodies levels directed towards tissue-specific antigens in serum samples of patients and control subjects by ELISA technique as reported recently. 7 For this purpose, the biological part of a "BioValsalva©" valve was homogenized and coated on ELISA plates as solid phase. In patients implanted with ga-fixed porcine heart valves, tissue-specific antibodies were highest elevated (1.73-fold versus controls, P<.0001)…”

Section: Resultsmentioning

confidence: 99%

“…4,6 Key players in this scenario are antibodies, which are either pre-formed or induced specifically by the implant. 7,8 Both types of antibodies recognize xeno-antigens and induce by complement activation, macrophage recruitment and T-/B-cell response the observed inflammatory and calcifying processes. 6 In this context, the αGal epitope is considered as the most important xeno-antigen, a carbohydrate residue which formation occurs in bacteria and in mammals except humans and Old World monkeys.…”

Section: Introductionmentioning

confidence: 99%

Antibody formation towards porcine tissue in patients implanted with crosslinked heart valves is directed to antigenic tissue proteins and αGal epitopes and is reduced in healthy vegetarian subjects

Böer

Buettner

Schridde

et al. 2017

Xenotransplantation

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The Immune Response to Crosslinked Tissue is Reduced in Decellularized Xenogeneic and Absent in Decellularized Allogeneic Heart Valves

Abstract: The strong humoral immune response to glutaraldehyde-fixed tissues is reduced in decellularized xenogeneic valves and almost absent in decellularized allogeneic tissue up to 4.5 years after implantation.

Cited by 25 publications

References 36 publications

Inflammation in tissue engineering: The Janus between engraftment and rejection

Inflammation in tissue engineering: The Janus between engraftment and rejection

Natural Scaffolds for Regenerative Medicine: Direct Determination of Detergents Entrapped in Decellularized Heart Valves

Antibody formation towards porcine tissue in patients implanted with crosslinked heart valves is directed to antigenic tissue proteins and αGal epitopes and is reduced in healthy vegetarian subjects

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