Subcutaneous administration of a neutralizing IL-1β antibody prolongs limb allograft survival.

Cytokine-expression profiles revealed IL-1ß highly upregulated in rejecting skin of limb allografts. We investigate the effect of intragraft treatment with a neutralizing IL-1β antibody in limb transplantation. Following allogenic hind-limb transplantation, Lewis rats were either left untreated or treated with anti-lymphocyte serum + tacrolimus (baseline); baseline immunosuppression + anti-IL-1β (1 mg/kg once/week, 6-8 subcutaneous injections) into the transplanted or contralateral limb.

Mesenchymal Stem Cells Enhance Nerve Regeneration in a Rat Sciatic Nerve Repair and Hindlimb Transplant Model.

This study investigates the efficacy of local and intravenous mesenchymal stem cell (MSC) administration to augment neuroregeneration in both a sciatic nerve cut-and-repair and rat hindlimb transplant model. Bone marrow-derived MSCs were harvested and purified from Brown-Norway (BN) rats. Sciatic nerve transections and repairs were performed in three groups of Lewis (LEW) rats: negative controls (n = 4), local MSCs (epineural) injection (n = 4), and systemic MSCs (intravenous) injection (n = 4).

Ischemia/reperfusion injury in vascularized tissue allotransplantation: tissue damage and clinical relevance.

Purpose Of Review: Ischemia and reperfusion injury (IRI) in vascularized tissue allotransplantation (VCA) remain largely undefined. Because VCA is comprised of different tissues, the sensitivity towards IRI may not be uniform. We, herein, attempt to address mechanistic aspects of IRI in VCA and provide a summary on potential technologies and targets for amelioration or treatment of IRI in this novel field.

Orthotopic Hind Limb Transplantation in the Mouse.

In vivo animal model systems, and in particular mouse models, have evolved into powerful and versatile scientific tools indispensable to basic and translational research in the field of transplantation medicine. A vast array of reagents is available exclusively in this setting, including mono- and polyclonal antibodies for both diagnostic and interventional applications. In addition, a vast number of genotyped, inbred, transgenic, and knock out strains allow detailed investigation of the individual contributions of humoral and cellular components to the complex interplay of an immune response and make the mouse the gold standard for immunological research.

A multiphase transitioning peptide hydrogel for suturing ultrasmall vessels.

Many surgeries are complicated by the need to anastomose, or reconnect, micrometre-scale vessels. Although suturing remains the gold standard for anastomosing vessels, it is difficult to place sutures correctly through collapsed lumen, making the procedure prone to failure. Here, we report a multiphase transitioning peptide hydrogel that can be injected into the lumen of vessels to facilitate suturing.

Exploring cell-based tolerance strategies for hand and face transplantation.

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.

Histomorphometric evaluation of ischemia-reperfusion injury and the effect of preservation solutions histidine-tryptophan-ketoglutarate and University of Wisconsin in limb transplantation.

Background: The effect of cold ischemia (CI) in vascularized composite allotransplantation is unknown. We herein assess tissue-specific damage, acceptable CI time, and the effect of preservation solutions in a syngenic rat hindlimb transplant model.

Methods: Lewis rat limbs were flushed and stored for 2, 10, or 30 hr CI in saline, histidine-tryptophan-ketoglutarate or University of Wisconsin preservation solution before transplantation.

Near-infrared lymphography as a minimally invasive modality for imaging lymphatic reconstitution in a rat orthotopic hind limb transplantation model.

Wider application of vascularized composite allotransplantation (VCA) is limited by the need for chronic immunosuppression. Recent data suggest that the lymphatic system plays an important role in mediating rejection. This study used near-infrared (NIR) lymphography to describe lymphatic reconstitution in a rat VCA model.

Targeting the Kv1.3 potassium channel for immunosuppression in vascularized composite allotransplantation - a pilot study.

Kv1.3-channels are critically involved in activation and function of effector memory T cells. Blocking Kv1.

Mechanisms and mediators of inflammation: potential models for skin rejection and targeted therapy in vascularized composite allotransplantation.

Vascularized composite allotransplantation (VCA) is an effective treatment option for patients suffering from limb loss or severe disfigurement. However, postoperative courses of VCA recipients have been complicated by skin rejection, and long-term immunosuppression remains a necessity for allograft survival. To widen the scope of this quality-of-life improving procedure minimization of immunosuppression in order to limit risks and side effects is needed.

Animal models for basic and translational research in reconstructive transplantation.

Reconstructive transplantation represents a bona fide option for select patients with devastating tissue loss, which could better restore the appearance, anatomy, and function than any other conventional treatment currently available. Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the potential side effects of chronic multidrug immunosuppression. Thus, any reconstructive measures to improve these non-life-threatening conditions must address a delicate balance of risks and benefits.

Histopathologic characterization of mild rejection (grade I) in skin biopsies of human hand allografts.

Mild skin rejection is a common observation in reconstructive transplantation. To enlighten the role of this inflammatory reaction we investigated markers for cellular and antibody mediated rejection, adhesion molecules and tolerance markers. Forty-seven skin biopsies (rejection grade I) of human hand allografts were investigated by immunohistochemistry (CD3, CD4, CD8, CD20, CD68, C4d, LFA-1, ICAM-1, E-selectin, P-selectin, VE-cadherin, HLA-DR, IDO, and Foxp3).