Toll-like receptor 2-modulating pectin-polymers in alginate-based microcapsules attenuate immune responses and support islet-xenograft survival

Hu, Shuxian; Kuwabara, Rei; Chica, Carlos E Navarro; Smink, Alexandra M.; Koster, T. David; Medina, Juan D.; Haan, Bart J. de; Beukema, Martin; Lakey, Jonathan R. T.; Garcı́a, Andrés J.; Vos, Paul de

doi:10.1016/j.biomaterials.2020.120460

Cited by 38 publications

(23 citation statements)

References 72 publications

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“…[12] This may lead to release of inflammatory molecules [6] that can diffuse into the microcapsule and induce islet cell death. [8] We have shown that this immune response directly after implantation may lead to up to 60% loss of the islet functional mass in the first 2 weeks after grafting even in the absence of adhesion of cells to the surface of the microcapsules. [8,13] The immediate immune response after implantation is difficult to manage by changing capsule characteristics as it starts with the mandatory surgery and dying cells in the intracapsular environment.…”

Section: Introductionmentioning

confidence: 94%

“…[8] We have shown that this immune response directly after implantation may lead to up to 60% loss of the islet functional mass in the first 2 weeks after grafting even in the absence of adhesion of cells to the surface of the microcapsules. [8,13] The immediate immune response after implantation is difficult to manage by changing capsule characteristics as it starts with the mandatory surgery and dying cells in the intracapsular environment. A temporary attenuation of immune responses in the immediate environment of the graft has been proposed as a solution.…”

Section: Introductionmentioning

confidence: 94%

“…[7] Within this approach, islets are enveloped in a biocompatible and semipermeable membrane that allows the ingress of nutrients and glucose and the egress of therapeutic molecules, waste products, and insulin. [8] This membrane also protects the islets from direct contact with immune cells and larger deleterious biomolecules such as antibodies. [7] By shielding the islets from the effects of the immune system, it is possible to avoid the use of chronic immunosuppression, but it might also contribute to a solution for the worldwide shortage of donors as encapsulation allows application of xenogeneic islets or islet cells obtained from progenitor cell sources.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Studies of Squalene‐Gusperimus Nanoparticles in Islet‐Containing Alginate Microcapsules to Regulate the Immune Response in the Immediate Posttransplant Period

Chica

Qin

Haan

et al. 2021

Advanced NanoBiomed Research

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Grafting of microencapsulated pancreatic islets has been proposed as an alternative to exogenous insulin for the treatment of type 1 diabetes mellitus. Microencapsulated islets are protected from direct contact with immune cells and larger immune‐active molecules such as immunoglobulins. Unfortunately, many islet cells in the microcapsules are lost in the immediate period after transplantation due to an early host immune response limiting long‐term function of the graft. Gusperimus has shown to reduce the inflammatory responses to grafted encapsulated islets, but it cannot be appropriately used because it is easily hydrolyzed leading to loss of activity. To temporarily modulate the inflammatory response directly after implantation and stabilize gusperimus, squalene‐gusperimus nanoparticles (Sq‐GusNPs) are developed and incorporated in human islets‐containing alginate‐based microcapsules. A prolonged and continuous release of gusperimus is achieved. This offers an anti‐inflammatory microenvironment in the vicinity of the microcapsules and a reduction of cytokine secretion by lipopolysaccharides‐activated human macrophages. Release of gusperimus from Sq‐GusNPs does not affect the in vitro viability or function of human pancreatic islets. The data illustrate that incorporation of Sq‐GusNPs in alginate microcapsules offers an opportunity to temporarily modulate the immediate immune response after the grafting procedure of encapsulated islets cells and reduce loss of islet cells.

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Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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In Vitro Studies of Squalene‐Gusperimus Nanoparticles in Islet‐Containing Alginate Microcapsules to Regulate the Immune Response in the Immediate Posttransplant Period

Chica

Qin

Haan

et al. 2021

Advanced NanoBiomed Research

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“…Specifically, TLR-3 and -9 could be inhibited by pectins isolated from unripe papayas due to high molecular weight structures [ 73 ], similar to what was previously observed with lemon pectins that inhibited the TLR-2 heterodimer formation with TLR-1, but not with TLR-6 [ 161 ]. Citrus pectin ranging from 18 to 69% DM (but without further structural details or suggestions) was able to inhibit TLR/MyD88 by oral administration in mice and decreased TLR-2 mediated immune response in rats when administered both in alginate microcapsules and directly at drinking water [ 162 ]. Administration of pectin samples and usage of checkpoint inhibitors could be powerful measures to assure immune responses in certain types of cancer [ 168 ].…”

Section: Should Gal-3 Inhibition Be the Main Biological Effect Expect...mentioning

confidence: 99%

The Complex Biological Effects of Pectin: Galectin-3 Targeting as Potential Human Health Improvement?

2022

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Galectin-3 is the only chimeric representative of the galectin family. Although galectin-3 has ubiquitous regulatory and physiological effects, there is a great number of pathological environments where galectin-3 cooperatively participates. Pectin is composed of different chemical structures, such as homogalacturonans, rhamnogalacturonans, and side chains. The study of pectin’s major structural aspects is fundamental to predicting the impact of pectin on human health, especially regarding distinct molecular modulation. One of the explored pectin’s biological activities is the possible galectin-3 protein regulation. The present review focuses on revealing the structure/function relationship of pectins, their fragments, and their biological effects. The discussion highlighted by this review shows different effects described within in vitro and in vivo experimental models, with interesting and sometimes contradictory results, especially regarding galectin-3 interaction. The review demonstrates that pectins are promissory food-derived molecules for different bioactive functions. However, galectin-3 inhibition by pectin had been stated in literature before, although it is not a fully understood, experimentally convincing, and commonly agreed issue. It is demonstrated that more studies focusing on structural analysis and its relation to the observed beneficial effects, as well as substantial propositions of cause and effect alongside robust data, are needed for different pectin molecules’ interactions with galectin-3.

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“…Several in vitro and preclinical studies aimed to improve encapsulated islets' survival and function over time. Mice models received islet-containing constructs comprising the release of trophic/proangiogenic molecules from encapsulating biomaterials [85], the incorporation of immunomodulatory molecules in materials [86], as well as the cotransplantation of islets with other cell types [87]. Tailoring the device topography [88] and conformational design (e.g., donut-shaped [89], fiber-shaped [90], or 3D macroporous structures [91]), biomaterial chemistry, and mechanical properties, as well as the inclusion of extracellular matrix proteins in the encapsulating matrix [85,88,92] have been explored as roadways to improve/extend transplanted islet function.…”

Section: Approaches Combining Biomaterials and Cellsmentioning

confidence: 99%

Engineering Strategies for Allogeneic Solid Tissue Acceptance

Sousa

Mano

Oliveira

2021

Trends in Molecular Medicine

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Systemic immunosuppressants have allowed the transplantation of life-saving organs. However, they cause deleterious effects and long-term graft failure. Strategies promoting allogeneic graft acceptance and the maintenance of immunological competence have been proposed.Cell-based tolerance-inducing strategies that preserve immune competence have already extended human allograft acceptance, although toxic side effects or difficult reproduction of observed effects in humans have counteracted their clinical translation.Localized tolerance/immunosuppression mediated through bioengineered setups comprising immunomodulatory biomaterials and/or tissue engineeringinspired tools already achieved allograft acceptance in murine models and are game changing in the field. Such advances have contributed to unveiling the complex interplay of immune cells and allogeneic transplants.

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Toll-like receptor 2-modulating pectin-polymers in alginate-based microcapsules attenuate immune responses and support islet-xenograft survival

Cited by 38 publications

References 72 publications

In Vitro Studies of Squalene‐Gusperimus Nanoparticles in Islet‐Containing Alginate Microcapsules to Regulate the Immune Response in the Immediate Posttransplant Period

In Vitro Studies of Squalene‐Gusperimus Nanoparticles in Islet‐Containing Alginate Microcapsules to Regulate the Immune Response in the Immediate Posttransplant Period

The Complex Biological Effects of Pectin: Galectin-3 Targeting as Potential Human Health Improvement?

Engineering Strategies for Allogeneic Solid Tissue Acceptance

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