Evaluation of the host immune response to decellularized lung scaffolds derived from α-Gal knockout pigs in a non-human primate model

Stahl, Elizabeth C.; Bonvillain, Ryan W.; Skillen, Clint D.; Burger, Brandon L.; Hara, Hidetaka; Lee, Whayoung; Trygg, Cynthia B.; Didier, Peter J.; Grasperge, Brooke; Pashos, Nicholas C.; Bunnell, Bruce A.; Bianchi, John; Ayares, David; Guthrie, Kelly; Brown, Bryan N.; Petersen, Thomas

doi:10.1016/j.biomaterials.2018.09.038

Cited by 59 publications

(43 citation statements)

References 38 publications

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“…studied the immunological effects of the decellularized ɑGal knock out porcine lung implants and compared them with native and decellularized wild type porcine lung implants for 8 weeks. The authors did not observe any significant differences between decellularized WT and KO scaffolds, although the removal of the ɑGal epitope delayed immune cell infiltration and reduced chronic T‐cell‐mediated reactions to the scaffolds .…”

Section: Immunogenicity and Its Implicationsmentioning

confidence: 90%

“…Attempts to increase the organ pool and developments in the field of tissue engineering have led to an increased interest in xenogeneic materials as potential organ sources . Simultaneously, the problem of the host immune response against the carbohydrates composing the porcine‐derived xenografts has been noted.…”

Section: Immunogenicity and Its Implicationsmentioning

confidence: 99%

“…As mentioned above, the immunogenicity of decellularized tissue has been investigated in various studies by performing allogenic or xenogenic implantation at different sides . These studies have provided proof of concept evidence.…”

Section: Problems and Future Challengesmentioning

confidence: 99%

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Strategies based on organ decellularization and recellularization

et al. 2019

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Summary Transplantation is the only curative treatment option available for patients suffering from end‐stage organ failure, improving their quality of life and long‐term survival. However, because of organ scarcity, only a small number of these patients actually benefit from transplantation. Alternative treatment options are needed to address this problem. The technique of whole‐organ decellularization and recellularization has attracted increasing attention in the last decade. Decellularization includes the removal of all cellular components from an organ, while simultaneously preserving the micro and macro anatomy of the extracellular matrix. These bioscaffolds are subsequently repopulated with patient‐derived cells, thus constructing a personalized neo‐organ and ideally eliminating the need for immunosuppression. However, crucial problems have not yet been satisfyingly addressed and remain to be resolved, such as organ and cell sources. In this review, we focus on the actual state of organ de‐ and recellularization, as well as the problems and future challenges.

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Section: Immunogenicity and Its Implicationsmentioning

confidence: 90%

Section: Immunogenicity and Its Implicationsmentioning

confidence: 99%

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Strategies based on organ decellularization and recellularization

et al. 2019

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“…Despite initial enthusiasm, xenogeneic organ transplantation studies performed with Gal knockout animals have resulted in acute rejection (Chen et al, ). In xenogeneic scaffold transplantation, however, scaffolds from the Gal knockout animal display a delayed immune cell infiltration and reduced inflammation (Stahl et al, ). Although encouraging, signs of inflammation are still present.…”

Section: Immunogenic Elements On Acellular Scaffoldsmentioning

confidence: 99%

“…This confounds translation of animal findings to humans (Mestas & Hughes, ; R. M. Wang et al, ). To overcome this problem, larger animal models closer to humans, including nonhuman primates and pigs, are being explored (Sakai et al, ; Stahl et al, ). In addition, a humanized mouse model that mimics the human immune response has been generated (Wang, Johnson, et al, ).…”

Section: Translational Limitations Of Biological Scaffoldsmentioning

confidence: 99%

Limitations of recellularized biological scaffolds for human transplantation

Bilodeau

Goltsis

Rogers

et al. 2020

J Tissue Eng Regen Med

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A shortage of donor organs for transplantation and the dependence of the recipients on immunosuppressive therapy have motivated researchers to consider alternative regenerative approaches. The answer may reside in acellular scaffolds generated from cadaveric human and animal tissues. Acellular scaffolds are expected to preserve the architectural and mechanical properties of the original organ, permitting cell attachment, growth, and differentiation. Although theoretically, the use of acellular scaffolds for transplantation should pose no threat to the recipient's immune system, experimental data have revealed significant immune responses to allogeneic and xenogeneic transplanted scaffolds. Herein, we review the various factors of the scaffold that could trigger an inflammatory and/or immune response, thereby compromising its use for human transplant therapy. In addition, we provide an overview of the major cell types that have been considered for recellularization of the scaffold and their potential contribution to triggering an immune response.

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Fabrication Strategies for Bioinspired and Functional Lung‐on‐Chips

Doryab,

Braig,

Jungst

et al. 2024

Adv Funct Materials

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Lung‐on‐chips (LoCs) are advanced microsystems designed to culture pulmonary cells under physiologically relevant conditions, including air–liquid interface, cell stretch, and shear stress. As the most promising preclinical models, the LoCs are aimed to reduce and ultimately replace conventional ineffective animal studies. Biomimetic and functional LoCs lead to more translational preclinical studies that effectively address unmet needs across therapeutic areas. A variety of cell‐ and scaffold‐based techniques are employed to establish biomimetic pulmonary cell models that closely resemble their in vivo counterparts, which is a challenging yet critical aspect of LoCs. Herein, the challenges encountered in biomimetic LoCs are discussed, and the future perspectives toward higher biomimicry using advanced biofabrication approaches are explored.

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Evaluation of the host immune response to decellularized lung scaffolds derived from α-Gal knockout pigs in a non-human primate model

Cited by 59 publications

References 38 publications

Strategies based on organ decellularization and recellularization

Strategies based on organ decellularization and recellularization

Limitations of recellularized biological scaffolds for human transplantation

Fabrication Strategies for Bioinspired and Functional Lung‐on‐Chips

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