Rapamycin-Conditioned Dendritic Cells Activated With Monophosphoryl Lipid-A Promote Allograft Acceptance
            <i>in vivo</i>

Campos-Acuña, Javier; Pérez, Francisco; Narváez, Edgar; Campos‐Mora, Mauricio; Gajardo, Tania; Catalán, Diego; Aguillón, Juan Carlos; Pino‐Lagos, Karina

doi:10.2217/imt.14.116

Cited by 8 publications

(7 citation statements)

References 33 publications

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“…Rapamycin (mTOR inhibitor) could suppress DC maturity with intermediate levels of MHC-II and costimulatory molecules ( 40 ). Campos-Acuña et al transferred Tol-DC conditioned by rapamycin and activated by mono-phosphoryl lipid A to a murine skin graft model, resulting in a longer allograft survival period, more Treg proliferation, and cytokine pattern modification ( 41 ). Dex is a steroid widely used for the prevention and treatment of organ rejection.…”

Section: The Ex Vivo Induction Of Tol-dcmentioning

confidence: 99%

“…Rapamycin, an mTOR blocker, has been widely used to prevent rejection after organ transplantation. Rapamycin-induced DC administration is shown to play an immunosuppressive role in skin transplantation ( 41 ). Polymerized allergoids conjugated to mannan (PM), which can induce the tolerance of DC, are thought to be vigorous vaccines for allergen-specific immunotherapy.…”

Section: The Metabolism Modification Of Tol-dcmentioning

confidence: 99%

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Tolerogenic Dendritic Cells: The Pearl of Immunotherapy in Organ Transplantation

et al. 2020

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Over a half century, organ transplantation has become an effective method for the treatment of end-stage visceral diseases. Although the application of immunosuppressants (IS) minimizes the rate of allograft rejection, the common use of IS bring many adverse effects to transplant patients. Moreover, true transplant tolerance is very rare in clinical practice. Dendritic cells (DCs) are thought to be the most potent antigen-presenting cells, which makes a bridge between innate and adaptive immunity. Among their subsets, a small portion of DCs with immunoregulatory function was known as tolerogenic DC (Tol-DC). Previous reports demonstrated the ability of adoptively transferred Tol-DC to approach transplant tolerance in animal models. In this study, we summarized the properties, ex vivo generation, metabolism, and clinical attempts of Tol-DC. Tol-DC is expected to become a substitute for IS to enable patients to achieve immune tolerance in the future.

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Section: The Ex Vivo Induction Of Tol-dcmentioning

confidence: 99%

Section: The Metabolism Modification Of Tol-dcmentioning

confidence: 99%

Tolerogenic Dendritic Cells: The Pearl of Immunotherapy in Organ Transplantation

et al. 2020

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“…The skin allograft model is known to be the most potent and convenient experimental model for the study of immunologically mediated tissue rejection. To counteract rejection responses, various studies have examined its validity for the assessment of allograft rejection [ 1 , 2 , 3 , 4 , 5 , 6 ]. Our present study confirms that BoTA promotes skin allograft survival and reduces the occurrence of acute rejection.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, identifying novel and safe immunosuppressants is of great importance to clinical practice. Research suggests that skin has the most pronounced immunogenicity, resulting in allograft rejection following transplantation [ 1–3 ]. Therefore, skin transplantation is used as a reliable model of allograft rejection.…”

Section: Introductionmentioning

confidence: 99%

Botulinum toxin A increases allograft tolerance in an experimental transplantation model: a preliminary study

et al. 2018

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BackgroundIdentifying novel and safe immunosuppressants is of crucial importance. Recently, there have been several studies revealing that botulinum toxin A significantly alleviates ischemia-reperfusion injuries.Emerging evidence shows that ischemia-reperfusion injuries contribute to innate immune activation, promoting rejection and inhibiting tolerance. Therefore, we hypothesized that a pretreatment with botulinum toxin A might decrease allograft rejection in a rat transplantation model. MethodsTwenty-four Lewis rats were randomly assigned to two groups consisting of 12 rats each, depending on whether skin allograft was performed after pretreatment with botulinum toxin A (BoTA group) or with normal saline (control group). The experimental group was pretreated with a subcutaneous injection of botulinum toxin A (10 IU), while the control group was pretreated with normal saline 5 days prior to surgery. The donor Brown-Norway rat dorsal skin was subsequently grafted to the recipient Lewis rats. The recipient wounds, measuring 2 cm × 2 cm, were made via dorsal skin excision through the panniculus carnosus. The donor skins of the same dimensions were obtained and transplanted onto the wounds and sutured with 4-0 nylon sutures. Mean graft survival time was measured in both groups. Quantitative reverse-transcriptase polymerase chain reaction and western blotting were performed to evaluate the gene/protein expression of CD4 and VEGF. ResultsThe mean graft survival time in the BoTA group was significantly longer than that of the control group (p=0.004). The relative mRNA and protein expression of CD4 was significantly lower in the BoTA group (p<0.001), while the relative mRNA and protein expression of VEGF was significantly higher in the BoTA group (p<0.001). ConclusionIn conclusion, our results show that botulinum toxin A prolongs the survival of skin allografts in a rat transplantation model.

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“…Another group characterized the ability of Rapa and monophosphoryl lipid A treated DC to prolong skin allograft survival, recruit FoxP3 + T cells to the allograft, and modulate the production of pro-inflammatory cytokines [120]. In a separate model of allogeneic heart transplant in rats, syngeneic tolDC injected on the day before surgery without pharmaceutical augmentation resulted in significantly prolonged graft survival [105].…”

Section: Regulatory T Cellsmentioning

confidence: 99%

Exploring cell-based tolerance strategies for hand and face transplantation

Fryer

Grahammer

Khalifian

et al. 2015

Expert Review of Clinical Immunology

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Broader clinical application of reconstructive hand and face transplantation is hindered by the need for lifelong immunosuppression for allograft maintenance. In this review, we summarize various cell-based approaches to tolerance induction currently under investigation in both clinical and pre-clinical models to alleviate the need for chronic immunosuppression. These include strategies to induce mixed hematopoietic chimerism, therapy with T and B regulatory cells, regulatory macrophages, tolerogenic dendritic cells, and mesenchymal stem cells. The vascularized, intragraft bone components inherent to reconstructive transplants serve as a continuous source of donor-derived hematopoietic cells, and make hand and face transplants uniquely well suited for cell-based approaches to tolerance that may ultimately tilt the risk-benefit balance for these life-changing, but not life-saving, procedures.

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Rapamycin-Conditioned Dendritic Cells Activated With Monophosphoryl Lipid-A Promote Allograft Acceptance in vivo

Abstract: Rapa-mDCs re-educate the inflammatory microenvironment, promoting skin-allograft survival.

Cited by 8 publications

References 33 publications

Tolerogenic Dendritic Cells: The Pearl of Immunotherapy in Organ Transplantation

Tolerogenic Dendritic Cells: The Pearl of Immunotherapy in Organ Transplantation

Botulinum toxin A increases allograft tolerance in an experimental transplantation model: a preliminary study

Exploring cell-based tolerance strategies for hand and face transplantation

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