Comparative evaluation of decellularized porcine liver matrices crosslinked with different chemical and natural crosslinking agents

Gao, Mengyu; Wang, Yujia; He, Yuting; Li, Yi; Wu, Qiong; Yang, Guang; Zhou, Yanyan; Wu, Dan; Bao, Ji; Bu, Hong

doi:10.1111/xen.12470

Cited by 34 publications

(27 citation statements)

References 39 publications

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“…However, in our study, the uncrosslinked matrix received the lowest immunogenicity results in xenogeneic subcutaneous/in-situ transplantation, while all crosslinked groups showed the infiltration of neutrophils/macrophages and the overexpressed TNF-a. It is worth mentioning that, consistent with previously studies, PC-and GP-crosslinked dUECM decreased the immunogenic reactions compared to GA group, exhibited a higher biocompatibility [18,35].…”

Section: Discussionsupporting

confidence: 89%

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Exploiting crosslinked decellularized matrix to achieve uterus regeneration and construction

Yao

Zheng

Lin

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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2020) Exploiting crosslinked decellularized matrix to achieve uterus regeneration and construction, Artificial Cells, Nanomedicine, and Biotechnology, 48:1, 218-229, ABSTRACTDecellularized extracellular matrix (dECM) has been considered as a promising scaffold in xenotransplantation, yet natural tissue dECM is often mechanically weak and rapidly degraded, compromising the outcomes. How to restore the mechanical strength and optimise the in vivo degradation, but maintain the microstructure and maximumly suppress the immune rejection, remains challenging. For this aim, we prepared and characterised various crosslinked decellularized rabbit uterus matrix (dUECM) and evaluated in vivo performance after uterus xenotransplantation from rabbit to rat. Naturally derived genipin (GP) and procyanidins (PC) were chosen to crosslink the dUECM, producing significant mechanical enhanced crosslinked-dUECM along with prolonged enzymatic degradation rate. Xenogeneic subcutaneous graft studies revealed that PC-and GP-crosslinked dUECM experienced significant cell infiltration and caused low immune reactions, indicating the desired biocompatibility. In vivo transplantation of GP-and PC-crosslinked dUECM to a uterus circular excised rat yielded excellent recellularization ability and promoted uterus regeneration after 90 days. While the reconstruction efficacy of crosslinked dUECM is highly depended on the crosslinking degree, crosslinking condition must be carefully evaluated to balance the role of crosslinked dECM in mechanical and biological support for tissue regeneration promotion. ARTICLE HISTORY

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Section: Discussionsupporting

confidence: 89%

“…Crosslinked decellularized tissue derived scaffold might suitably improve the mechanical properties and biocompatibility, and reduce immune reaction to promote organ regeneration. However, currently, there are only very few studies evaluated the degreadation and biocompability of crosslinked dECM in vivo [18].…”

Section: Introductionmentioning

confidence: 99%

Exploiting crosslinked decellularized matrix to achieve uterus regeneration and construction

Yao

Zheng

Lin

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Neutrophil recruitment to xenografts leads to local tissue destruction by the release of enzymes and reactive oxygen species. In the current issue, Gao et al demonstrated that porcine cytokines, including interleukin (IL)‐6, IL‐1beta, and TNF‐alpha, activate human umbilical vein endothelial cells (HUVECs) and promoted gene transcription, linking porcine gene expression post‐transplant with inflammatory responses . The authors note that the above‐mentioned cytokines and their receptors are sufficiently homologous between pig and human to a significant factor.…”

Section: Basic Researchmentioning

confidence: 98%

Xenotransplantation literature update, September/October 2018

Taylor

Levy

Burlak

2018

Xenotransplantation

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Damage from hypoxia is a significant hurdle for effect islet transplantation. Past studies have shown that porcine islet cells are protected from hypoxic damage when cultured with human mesenchymal stem cells (MSCs). To better understand how MSCs protect islet cells, Nie et al evaluated the contribution of MSC-secreted factors. MSC-conditioned media (CM) and exosomes reduced cellular apoptosis leading to enhanced cell survival. 1 Additionally, CM and exosomes activated transcriptional programs in islet cells associated with hypoxia tolerance, including hypoxia-inducible factor 1 alpha (Hif1-alpha). The review article by Smith et al 2 focuses on cellular encapsulation to protect recipients from antigenic donor grafts. They discuss new discoveries, issues, and strategies for wrapping up the donor cells, including an overview of device characteristics. 2 of 2 | TAYLOR eT AL. Non-Gal antigens in porcine cells have long been of interest for engineering an optimal porcine donor graft to use in clinical xenotransplantation. The review written by Byrne et al provides detailed and supportive information on a critical non-Gal antigen, B4GalNT2, and illustrates that when deleted, porcine cells are targeted less by the immune system. 10 2 | IMMUNE SUPPRE SS ION Corneal transplants using porcine tissues are a promising solution to a global need for corneal tissue to correct blindness. Descemet's membrane endothelial keratoplasty (DMEK) is an innovative transplantation technique that benefits from low rejection rates and requisite immunosuppression and results in superior vision recovery compared to other surgical techniques. Indeed, in current issue, Kim et al 11 demonstrate that immunosuppression with the common agent tacrolimus can lead to asymptomatic thrombotic microangiopathy that can lead to a number of problems including organ damage. Minimizing the need for immunosuppression by improved graft quality, genetics, and preparation may therefore enhance tissue survival long term. Liu et al 12 tested the feasibility of porcine xenografts using the DMEK technique. Here, the group used two techniques, mechanical stripping and liquid bubble, to prepare the ultra-thin DMEK prior to transplantation. The data, including a comparison of endothelial growth, were promising and indicate that corneal xenografts using DMEK are a viable future option. The authors plan next to test the xeno-DMEK in a non-human primate model. Successful xenotransplantation currently requires immunosuppression. Unfortunately, the immunosuppression regimen may be lethal, by a yet unidentified mechanism, though often linked with anti-CD154 antibody treatment. Ock et al 13 used a non-human primate model (cynomolgus macaques) to evaluate the transcriptional changes prior to and after the standard immunosuppression protocol for porcine cardiac xenotransplantation (alpha-1,3-galactosyltransferase KO pigs). The regimen included cobra venom factor, anti-thymocyte globulin, and rituximab, in the presence or absence of anti-CD154 antibodies. The authors identified a...

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“…The extensive exploitation of pig livers is associated with both their broad accessibility, as well for the dimensions within a range consistent with the size of human liver. For these reasons, several studies organizations have investigated their application for liver bioengineering [71][72][73].…”

Section: Large Animal Modelmentioning

confidence: 99%

A Hepatic Scaffold from Decellularized Liver Tissue: Food for Thought

et al. 2019

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Allogeneic liver transplantation is still deemed the gold standard solution for end-stage organ failure; however, donor organ shortages have led to extended waiting lists for organ transplants. In order to overcome the lack of donors, the development of new therapeutic options is mandatory. In the last several years, organ bioengineering has been extensively explored to provide transplantable tissues or whole organs with the final goal of creating a three-dimensional growth microenvironment mimicking the native structure. It has been frequently reported that an extracellular matrix-based scaffold offers a structural support and important biological molecules that could help cellular proliferation during the recellularization process. The aim of the present review is to underline the recent developments in cell-on-scaffold technology for liver bioengineering, taking into account: (1) biological and synthetic scaffolds; (2) animal and human tissue decellularization; (3) scaffold recellularization; (4) 3D bioprinting; and (5) organoid technology. Future possible clinical applications in regenerative medicine for liver tissue engineering and for drug testing were underlined and dissected.

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Comparative evaluation of decellularized porcine liver matrices crosslinked with different chemical and natural crosslinking agents

Cited by 34 publications

References 39 publications

Exploiting crosslinked decellularized matrix to achieve uterus regeneration and construction

Exploiting crosslinked decellularized matrix to achieve uterus regeneration and construction

Xenotransplantation literature update, September/October 2018

A Hepatic Scaffold from Decellularized Liver Tissue: Food for Thought

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