Immune molecular profiling of whole blood drawn from a non‐human primate cardiac xenograft model treated with anti‐<scp>CD</scp>154 monoclonal antibodies

Ock, Sun‐A; Oh, Keon Bong; Hwang, Seongsoo; Yun, Ik Jin; Ahn, Curie; Chee, Hyun Ken; Kim, Hwajung; Ullah, Imran; Im, Gi Sun; Park, Eung Woo

doi:10.1111/xen.12392

Cited by 3 publications

(4 citation statements)

References 33 publications

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“…Although efficacy in vivo is not reported yet, this approach holds some promises as recruiting Treg cells by intramuscular co-transplantation of islets with a plasmid encoding Treg cell specific chemokine CCL22 was efficacious in preventing graft rejection (Vågesjö et al, 2015). Some success has also been shown in xenotransplantation with blockade of the costimulatory pathway of CD40/CD154, which inhibited T cell and B cell signaling (Ock et al, 2018; Do et al, 2019). In mice treated with this approach, increased numbers of Treg cells and an elevated anti-inflammatory cytokine profile was found around a porcine islet grafts (Wu et al, 2017).…”

Section: Accessory Cell Strategies To Reduce Tissue Responsesmentioning

confidence: 99%

Polymeric Approaches to Reduce Tissue Responses Against Devices Applied for Islet-Cell Encapsulation

Vos

2019

Front. Bioeng. Biotechnol.

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Immunoisolation of pancreatic islets is a technology in which islets are encapsulated in semipermeable but immunoprotective polymeric membranes. The technology allows for successful transplantation of insulin-producing cells in the absence of immunosuppression. Different approaches of immunoisolation are currently under development. These approaches involve intravascular devices that are connected to the bloodstream and extravascular devices that can be distinguished in micro- and macrocapsules and are usually implanted in the peritoneal cavity or under the skin. The technology has been subject of intense fundamental research in the past decade. It has co-evolved with novel replenishable cell sources for cure of diseases such as Type 1 Diabetes Mellitus that need to be protected for the host immune system. Although the devices have shown significant success in animal models and even in human safety studies most technologies still suffer from undesired tissue responses in the host. Here we review the past and current approaches to modulate and reduce tissue responses against extravascular cell-containing micro- and macrocapsules with a focus on rational choices for polymer (combinations). Choices for polymers but also choices for crosslinking agents that induce more stable and biocompatible capsules are discussed. Combining beneficial properties of molecules in diblock polymers or application of these molecules or other anti-biofouling molecules have been reviewed. Emerging are also the principles of polymer brushes that prevent protein and cell-adhesion. Recently also immunomodulating biomaterials that bind to specific immune receptors have entered the field. Several natural and synthetic polymers and even combinations of these polymers have demonstrated significant improvement in outcomes of encapsulated grafts. Adequate polymeric surface properties have been shown to be essential but how the surface should be composed to avoid host responses remains to be identified. Current insight is that optimal biocompatible devices can be created which raises optimism that immunoisolating devices can be created that allows for long term survival of encapsulated replenishable insulin-producing cell sources for treatment of Type 1 Diabetes Mellitus.

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Section: Accessory Cell Strategies To Reduce Tissue Responsesmentioning

confidence: 99%

Polymeric Approaches to Reduce Tissue Responses Against Devices Applied for Islet-Cell Encapsulation

Vos

2019

Front. Bioeng. Biotechnol.

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“…Using an ex vivo porcine lung perfusion model, Kim et al demonstrated that aurintricarboxylic acid could attenuate hyperacute rejection by preventing coagulation perturbation and showed that pretreatment of the donor pig with 1‐deamino‐8‐D‐arginine vasopressin (DDAVP) decreased platelet activation as well as complement/coagulation activation resulting in the attenuation of systemic intravascular coagulation . Recently, Ock et al reported that GTKO pig hearts heterotopically transplanted into NHPs with anti‐CD154 Ab‐based immunosuppression survived from 11 to 24 days, and they performed molecular immunology profiling of the whole blood drawn from the recipient …”

Section: Research Activities In Xenotransplantationmentioning

confidence: 99%

“…37 Recently, Ock et al reported that GTKO pig hearts heterotopically transplanted into NHPs with anti-CD154 Ab-based immunosuppression survived from 11 to 24 days, 38 and they performed molecular immunology profiling of the whole blood drawn from the recipient. 39…”

Section: Pancreatic Islet and Cornea Xenotransplantationmentioning

confidence: 99%

Current status of xenotransplantation in South Korea

Park

Shin

Min

et al. 2019

Xenotransplantation

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“…Unfortunately, the immunosuppression regimen may be lethal, by a yet unidentified mechanism, though often linked with anti‐CD154 antibody treatment. Ock et al 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.…”

Section: Immune Suppressionmentioning

confidence: 99%

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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Immune molecular profiling of whole blood drawn from a non‐human primate cardiac xenograft model treated with anti‐CD154 monoclonal antibodies

Cited by 3 publications

References 33 publications

Polymeric Approaches to Reduce Tissue Responses Against Devices Applied for Islet-Cell Encapsulation

Polymeric Approaches to Reduce Tissue Responses Against Devices Applied for Islet-Cell Encapsulation

Current status of xenotransplantation in South Korea

Xenotransplantation literature update, September/October 2018

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