Absence of Immune Responses with Xenogeneic Collagen and Elastin

Abstract

Novel tissue-engineering approaches for cardiovascular matrices based on xenogeneic extracellular matrix protein (ECMp) constituents require a detailed evaluation of their interaction with essential immune cell subsets playing a role in innate or adaptive immunity. Therefore, in this study, the effects of xenogeneic (porcine, bovine) collagen type I and elastin as the two main components of the heart valve ECM were analyzed in comparison to their human equivalents. First, their potential to induce maturation and cytokine secretion of human dendritic cells (DC) was tested by flow cytometry. Second, the influence on proliferation and cytokine release of purified human B and T cells was measured. We could demonstrate that xenogeneic collagen type I and elastin are not able to trigger the maturation of DC as verified by the lack of CD83 induction accompanied by a low tumor necrosis factor-a release. Moreover, both ECMp showed no effect on the proliferation and the interleukin-6 release of either unstimulated or prestimulated B cells. Additionally, anti-CD3-induced purified T cell proliferation and secretion of cytokines was not affected. All in vitro data verify the low immunogenicity of porcine and bovine collagen type I and elastin and favor their suitability for tissue-engineered scaffolds.

Activation of dendritic cells by crosslinked collagen hydrogels (artificial corneas) varies with their composition

“…In general, therefore, natural collagen and other structural matrix proteins do not induce immune responses and are probably tolerogenic (Bayrak, Prüger, Stock, & Seifert, ). Similarly, the fabricated matrices studied here are probably tolerogenic, but variably so, depending on the respective gel chemistry.…”

“…Similarly, the fabricated matrices studied here are probably tolerogenic, but variably so, depending on the respective gel chemistry. Soluble collagen bound to tissue culture plastic is known to be non‐activating for DC (Bayrak et al, ), and this is mediated via the collagen receptor LAIR‐1 (Leslee Sprague et al, ). In the present study, both the natural matrices and the engineered collagen gels induced upregulation of LAIR‐1, although to different degrees (Figure a).…”

Advancing biomaterials of human origin for tissue engineering

“…The attractive properties of collagen for use in tissue engineering biomaterials include, but are not limited to, its good biocompatibility; low antigenicity; and tailored mechanical, degradation and water uptake properties due to its ability to be crosslinked through chemical glycation procedures or heat treatments [267]. Compared with protein constituents extracted from animal tissues, human-derived collagen for scaffold production in tissue engineering lowers the risk of hypersensitivity and immunogenicity, but the potential to cause pathogenic contamination and/or disease transmission still exists [307]. In this respect, recombinant human collagen based on plant materials provides an alternate natural collagen source without the risk of disease transmission or concerns regarding variability [308].…”

Immune responses to bioengineered organs

“…A recent review from Keane and Badylak [65 ▪▪ ] summarizes the current immunological implications associated with the use of biological scaffolds. Indeed, several reports describe that each of the ECM components activate the innate immune response: proteoglycans (heparan sulfate, chondroitin sulfate and keratan sulfate) [66]; nonproteoglycan polysaccharide (hyaluronic acid) [67 ▪ ]; fibers (collagen and elastin) [68,69] and others (fibronectin and laminin) [70]. The immune reactivity against the ECM is of special interest in the context of chronic rejection, as this process is not prevented by current immunosuppressive therapy and involves multiple immunological processes in which graft ECM is slowly destroyed, whereas graft blood vessels are obstructed by the deposition of collagen [71].…”