Genetic Modification of Limbs Using<i>Ex Vivo</i>Machine Perfusion

Valdivia, Emilio; Rother, Tamina; Yuzefovych, Yuliia; Hack, Franziska; Wenzel, Nadine; Blasczyk, Rainer; Krezdorn, Nicco; Figueiredo, Constança

doi:10.1089/hum.2021.199

Cited by 8 publications

(5 citation statements)

References 60 publications

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“…Forati et al . reported that adding Graphene oxide into PES nanocomposites notably enhanced PES films’ mechanical properties and thermal stability 43 . Feng Li and coworkers also reported that loading TiO 2 NPs in PES texture improved the membrane mechanical strength 44 .…”

Section: Resultsmentioning

confidence: 99%

Designing of a new transdermal antibiotic delivery polymeric membrane modified by functionalized SBA-15 mesoporous filler

Samari,

Kashanian,

Zinadini

et al. 2024

Sci Rep

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A new drug delivery system using an asymmetric polyethersulfone (PES) membrane modified by SBA-15 and glutamine-modified SBA-15 (SBA-Q) was prepared in this study by the aim of azithromycin delivery enhancement in both in vitro and ex vivo experiments. The research focused on optimizing membrane performance by adjusting critical parameters including drug concentration, membrane thickness, modifier percentage, polymer percentage, and pore maker percentage. To characterize the fabricated membranes, various techniques were employed, including scanning electron microscopy, water contact angle, and tensile strength assessments. Following optimization, membrane composition of 17% PES, 2% polyvinylpyrrolidone, 1% SBA-15, and 0.5% SBA-Q emerged as the most effective. The optimized membranes demonstrated a substantial increase in drug release (906 mg/L) compared to the unmodified membrane (440 mg/L). The unique membrane structure, with a dense top layer facilitating sustained drug release and a porous sub-layer acting as a drug reservoir, contributed to this improvement. Biocompatibility assessments, antibacterial activity analysis, blood compatibility tests, and post-diffusion tissue integrity evaluations confirmed the promising biocompatibility of the optimized membranes. Moreover, long-term performance evaluations involving ten repeated usages underscored the reusability of the optimized membrane, highlighting its potential for sustained and reliable drug delivery applications.

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Section: Resultsmentioning

confidence: 99%

Designing of a new transdermal antibiotic delivery polymeric membrane modified by functionalized SBA-15 mesoporous filler

Samari,

Kashanian,

Zinadini

et al. 2024

Sci Rep

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show abstract

“…In the allogeneic transplantation model, silencing MHC expression on different cell types, tissues, and organs was shown to be feasible and contributed to decreasing the susceptibility to antibody-mediated cellular and complement-dependent cytotoxicity. Furthermore, silencing MHC expression was shown to induce weaker T-cell allogeneic immune responses and contribute to the significantly lower secretion of pro-inflammatory cytokines of IL-6 and IFN-γ [ 18 , 19 , 38 , 39 ]. IL-6 is involved in innate immune responses as well as in adaptive immunity.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Swine Leukocyte Antigen Expression Decreases the Strength of Xenogeneic Immune Responses towards Renal Proximal Tubular Epithelial Cells

Schmalkuche

Schwinzer

Wenzel

et al. 2023

IJMS

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Xenotransplantation reemerged as a promising alternative to conventional transplantation enlarging the available organ pool. However, success of xenotransplantation depends on the design and selection of specific genetic modifications and on the development of robust assays allowing for a precise assessment of tissue-specific immune responses. Nevertheless, cell-based assays are often compromised by low proliferative capacity of primary cells. Proximal tubular epithelial cells (PTECs) play a crucial role in kidney function. Here, we generated immortalized PTECs (imPTECs) by overexpression of simian virus 40 T large antigen. ImPTECs not only showed typical morphology and phenotype, but, in contrast to primary PTECs, they maintained steady cell cycling rates and functionality. Furthermore, swine leukocyte antigen (SLA) class I and class II transcript levels were reduced by up to 85% after transduction with lentiviral vectors encoding for short hairpin RNAs targeting β2-microglobulin and the class II transactivator. This contributed to reducing xenogeneic T-cell cytotoxicity (p < 0.01) and decreasing secretion of pro-inflammatory cytokines such as IL-6 and IFN-γ. This study showed the feasibility of generating highly proliferative PTECs and the development of tissue-specific immunomonitoring assays. Silencing SLA expression on PTECs was demonstrated to be an effective strategy to prevent xenogeneic cellular immune responses and may strongly support graft survival after xenotransplantation.

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“…In the allogeneic transplantation model, silencing MHC expression in different cell types, tissues and organs showed to be feasible and contributed to decreasing the susceptibility to antibody-mediated cellular and complement-dependent cytotoxicity. Furthermore, silencing MHC expression showed to induce weaker T-cell allogeneic immune responses and contribute to the signi cantly lower secretion of pro-in ammatory cytokines of IL-6 and IFN-γ 17,18,35,36 . IL-6 is involved in innate immune responses as well as adaptive immunity.…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific cells generated to predict xenogeneic immune responses demonstrate that SLA-downregulated kidney proximal tubular epithelial cells are low immunogenic

Schmalkuche

Schwinzer

Wenzel

et al. 2023

Preprint

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Patients with kidney failure depend on transplantation as the only curative option. Xenotransplantation re-emerged as a promising alternative to enlarge the available organ pool. However, the success of xenotransplantation depends on the design and selection of specific genetic modifications and on the development of robust assays allowing for a precise assessment of tissue-specific immune responses. Nevertheless, cell-based assays are often compromised by the low proliferative capacity of primary cells. Proximal tubular epithelial cells (PTECs) play a crucial role in kidney function. Here, we immortalized PTEC (imPTEC) by overexpression of simian virus 40 T large antigen. imPTEC showed typical morphology, phenotype, and functionality, but maintained steady cell cycling rates. Furthermore, SLA class I and class II transcript levels were reduced by up to 85% after transduction with lentiviral vectors encoding for shRNAs targeting β2-microglobulin and the class II transactivator. This contributed to reduce xenogeneic T-cell cytotoxicity (P = 0.0069) and decrease pro-inflammatory cytokine secretion such as IL-6 and IFN-γ. This study showed the feasibility to generate highly proliferative renal tubular cells and the development of tissue-specific immunomonitoring assays. Silencing SLA expression on PTEC demonstrated to be an effective strategy to prevent xenogeneic cellular immune responses and may strongly support graft survival after xenotransplantation.

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Genetic Modification of Limbs UsingEx VivoMachine Perfusion

Cited by 8 publications

References 60 publications

Designing of a new transdermal antibiotic delivery polymeric membrane modified by functionalized SBA-15 mesoporous filler

Designing of a new transdermal antibiotic delivery polymeric membrane modified by functionalized SBA-15 mesoporous filler

Downregulation of Swine Leukocyte Antigen Expression Decreases the Strength of Xenogeneic Immune Responses towards Renal Proximal Tubular Epithelial Cells

Tissue-specific cells generated to predict xenogeneic immune responses demonstrate that SLA-downregulated kidney proximal tubular epithelial cells are low immunogenic

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