<i>In vitro</i> evaluation of the bioactive factors preserved in porcine small intestinal submucosa through cellular biological approaches

Yang, Bin; Zhou, Liuhua; Sun, Zhen; Yang, Rong; Chen, Yun; Dai, Yutian

doi:10.1002/jbm.a.32534

Cited by 37 publications

(23 citation statements)

References 44 publications

(109 reference statements)

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“…These peptides were found to display chemoattractant potential for several cell types in vitro and in vivo, including endothelial cells and multipotential progenitor cells that participate in the remodeling of the ECM. [70][71][72] However, extensive production of anti-non gal antibodies in response to various immunogenic ECM proteins and proteoglycans may result in binding of these antibodies to the ECM implant and accelerate its destruction by macrophages binding to such antibodies complexed with ECM molecules. This will result in hindering stem cell/ECM interaction, elimination of the implant and possibly in the default process of fibrosis, rather than appropriate remodeling and regeneration of the ECM.…”

Section: Human Anti-non Gal Antibody Response To Mammalian Implant Prmentioning

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: Human Anti-non Gal Antibody Response To Mammalian Implant Prmentioning

confidence: 99%

Avoiding Detrimental Human Immune Response Against Mammalian Extracellular Matrix Implants

Galili

2015

Tissue Engineering Part B: Reviews

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“…observed that SIS can stimulate bladder smooth muscle cells and human umbilical vein endothelial cells to attach, proliferate and migrate in vitro . [31] Li et al . showed that small molecular weight peptides released by SIS are biologically active with respect to recruitment of murine endothelial cells in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

An injectable nucleus pulposus cell-modified decellularized scaffold: biocompatible material for prevention of disc degeneration

et al. 2017

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We developed a nucleus pulposus cell (NPC)-modulated decellularized small intestinal submucosa (SIS) scaffold, and assessed the ability of this material to prevent Intervertebral disc degeneration (IVD) degeneration. Decellularized porcine SIS was squashed into particles and the biological safety and efficiency of these particles were evaluated. Next, SIS particles were seeded with rabbit NPCs, cultured for two months in vitro, decellularized again and suspended for intervertebral injection. We demonstrated that use of the decellularization protocol resulted in the removal of cellular components with maximal retention of extracellular matrix. The xenogeneic decellularized SIS did not display cytotoxicity in vitro and its application prevented NPC degradation. Furthermore, the xenogeneic SIS microparticles were effective in preventing IVD progression in vivo in a rabbit disc degeneration model. In conclusion, our study describes an optimized method for decellularized SIS preparation and demonstrated that the material is safe and effective for treating IVD degeneration.

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“…SIS possesses a mixture of bioactive factors including cell adhesion factors, mitogenic factors, chemotactic cytokines, and angiogenic factors [10]. In 1966, it was first clinically used for replacement of the inferior vena cava [24].…”

Section: Discussionmentioning

confidence: 99%

“…Porcine-derived small intestinal submucosa (SIS) is one such decellularized, collagen-rich bioscaffold. It has been reported to contain functional growth factors considered vital for tissue restoration [7][8][9] and to preserve a mixture of bioactive factors including cell adhesion factors, mitogenic factors, chemotactic cytokines, and angiogenic factors [8,10]. Several reports have described the utility of SIS in intestinal tissue engineering using animal models [11][12][13][14][15][16].…”

mentioning

confidence: 96%

Proposal of intestinal tissue engineering combined with Bianchi’s procedure

Nakao

Ueno

Oga

et al. 2015

Journal of Pediatric Surgery

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In vitro evaluation of the bioactive factors preserved in porcine small intestinal submucosa through cellular biological approaches

Cited by 37 publications

References 44 publications

Avoiding Detrimental Human Immune Response Against Mammalian Extracellular Matrix Implants

Avoiding Detrimental Human Immune Response Against Mammalian Extracellular Matrix Implants

An injectable nucleus pulposus cell-modified decellularized scaffold: biocompatible material for prevention of disc degeneration

Proposal of intestinal tissue engineering combined with Bianchi’s procedure

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