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Histological characteristics of acute rejection in vascularized allografts of bone.

Using a genetically defined rat model for the heterotopic transplantation of a vascularized knee in the rat, histological and histochemical studies of acute rejection in vascularized allografts of bone were carried out. The graft consisted of the knee joint with the distal end of the femur, the proximal part of the tibia, the cartilaginous growth plates, the articular cartilage, and a minimum cuff of muscle, which was transferred to a location under the abdominal skin. A total of 160 transplants, including vascularized and non-vascularized isografts, vascularized and non-vascularized allograft…

Normoglycemia after reflux of islet-containing pancreatic fragments into the splenic vascular bed in dogs.

Canine pancreata obtained at total pancreatectomy were cannulated via the ducts and perfused with collagenase to prepare a tissue suspension that was isografted into the spleen (preparation congruent to 2 h, mean graft vol = 10 +/- 1 ml containing 24% of the B-cell mass/pancreas). In 13 dogs the tissue was implanted by reflux into terminal splenic veins: two died postoperatively, and in two the intrasplenic vein wall was inadvertently punctured during cannulation. In the remaining nine, mean fasting blood glucose (BG) was less than or equal to 150 mg/dl initially; one was killed at 2 wk (diste

Local Application of Isogenic Adipose-Derived Stem Cells Restores Bone Healing Capacity in a Type 2 Diabetes Model.

UNLABELLED: Bone regeneration is typically a reliable process without scar formation. The endocrine disease type 2 diabetes prolongs and impairs this healing process. In a previous work, we showed that angiogenesis and osteogenesis-essential steps of bone regeneration-are deteriorated, accompanied by reduced proliferation in type 2 diabetic bone regeneration. The aim of the study was to improve these mechanisms by local application of adipose-derived stem cells (ASCs) and facilitate bone regeneration in impaired diabetic bone regeneration. The availability of ASCs in great numbers and the rela

Morphology and immunohistochemistry of rat aortic grafts.

Allotransplantation (TPL) of the abdominal aortic segments of BN donors was performed in 32 Lewis recipients with or without cyclosporin A ( … ersisted in the allografts but disappeared from the intima and was reduced in the adventitia of the isografts after four and five months. Disseminated ED1+ activated macrophages were the most prominent population of infiltrates whereas modest numbers of adventitial ED2+ tissue macrophages remained constant throughout the intervals examined. CD4+ cells (foca …

Antibodies against complement component C5 prevent antibody-mediated rejection after lung transplantation in murine orthotopic models with skin-graft-induced pre-sensitization.

OBJECTIVE: Antibody-mediated rejection (AMR) could induce acute or chronic graft failure during organ transplantation. Several reports have shown that anti-C5 antibodies are effective against AMR after kidney transplantation. However, few reports have assessed the efficacy of anti-C5 antibodies against AMR after lung transplantation. Therefore, this study aimed to evaluate the efficacy of this novel therapy against AMR after lung transplantation. METHODS: BALB/c and C57BL/6 mice were used as donors and recipients. One group was pre-sensitized (PS) by skin transplantation 14 days before lung t

The CLEC-2-podoplanin axis inhibits dendritic cells migration and prolongs allograft survival in mice.

BACKGROUND: Dendritic cell (DC) migration-triggered T cell activation is a pivotal event in transplant rejection. Previous studies have established a critical role of the C-type lectin receptor 2（CLEC-2）and podoplanin (PDPN) axis in regulating DC migration. We therefore hypothesized that targeting CLEC-2-PDPN axis could prolong allograft survival in mice by impairing DC migration. MATERIALS AND METHODS: Bioinformatics analysis was performed to assess differential CLEC-2 expression between allograft and isograft tissues and to identify potential associated biological processes. Bone marrow-der

A Study on the Outcome of Myringoplasty in Small to Medium Sized Perforations Using Collagen Sheet as Graft Material.

Chronic Otitis Media is a global health problem causing significant morbidity of life. Various medical and surgical treatment modalities are being used for the treatment of Chronic Otitis Media. Surgical treatment is the definitive option which includes different surgical procedures, all of which have been designed to attain the same goals of eradicating disease and achieve a safe and dry ear with closure of tympanic membrane perforations. Various graft materials are being used for the closure of tympanic membrane perforations like autografts, isografts, allografts and xenografts, each having …

Homograft tympanoplasty in perspective. A long-term clinical-histologic study of formalin-fixed tympanic membranes used for the reconstruction of 125 severely damaged middle ears.

This seven and a half year clinical-histologic study evaluates the effectiveness of buffered, formaldehyde-fixed homograft tympanic membranes for reconstructing the severely damaged middle ear in 125 consecutive patients. Indications for use of homograft tympanoplasty were limited to those cases in which standard tympanoplasty had already failed to produce a satisfactory hearing or anatomic result (i.e., recurrent perforations or draining radical mastoidectomy cavity), or to those cases in which there was a high risk of unsatisfactory result with standard tympanoplasty techniques (i.e., total

Orthogonal targeting of osteoclasts and myeloma cells for radionuclide stimulated dynamic therapy induces multidimensional cell death pathways.

Rationale: Multiple myeloma (MM) is a multifocal malignancy of bone marrow plasma cells, characterized by vicious cycles of remission and relapse that eventually culminate in death. The disease remains mostly incurable largely due to the complex interactions between the bone microenvironment (BME) and MM cells (MMC). In the "vicious cycle" of bone disease, abnormal activation of osteoclasts (OCs) by MMC causes severe osteolysis, promotes immune evasion, and stimulates the growth of MMC. Disrupting these cancer-stroma interactions would enhance treatment response. Methods: To disrupt this cycle

Skin derived precursor Schwann cells improve behavioral recovery for acute and delayed nerve repair.

Previous work has shown that infusion of skin-derived precursors pre-differentiated into Schwann cells (SKP-SCs) can remyelinate injured and regenerating axons, and improve indices of axonal regeneration and electrophysiological parameters in rodents. We hypothesized that SKP-SC therapy would improve behavioral outcomes following nerve injury repair and tested this in a pre-clinical trial in 90 rats. A model of sciatic nerve injury and acellular graft repair was used to compare injected SKP-SCs to nerve-derived Schwann cells or media, and each was compared to the gold standard nerve isograft r

Donor and recipient leukocytes in organ allografts of recipients with variable donor-specific tolerance: with particular reference to chronic rejection.

We have attributed organ engraftment to clonal exhaustion-deletion of host-versus-graft and graft-versus-host reactions that are reciprocall … ents of groups 3 through 6. Nevertheless, all of the long-surviving cardiac allografts (but not the isografts in group 1) were the targets of an immune reaction at 5 days, reflected by dramatic increases in the ratio of leukocytes to nonleukocyte nucleated cells from normal values of 1:5-1:6 to 1:1-5:1 and by manifold other evidence of a major inflammatory …

Glutathione reductase-mediated thiol oxidative stress suppresses metastasis of murine melanoma cells.

Malignant melanoma is a highly metastatic and life-threatening cancer. Reactive oxygen species (ROS) play important roles in cancer initiation and progression including metastasis. It has been reported that the oxidative stress spontaneously generated in circulating melanoma cells was able to suppress distant metastasis in vivo. However, little is known regarding the effects and mechanism of glutathione reductase (GR) inhibition-induced oxidative stress in regulation of melanoma metastasis. Here, we demonstrate that GR inhibition generates oxidative stress and suppresses lung metastasis and su

[Establishment of obliterative bronchiolitis in allo-trachea transplant model of rat and detection of its pathogenesis preliminarily].

OBJECTIVE: To establish an animal model of obliterative bronchiolitis (OB) after lung transplantation and investigate the pathogenesis preli … between Group II and III in IFN-gamma, IL-4, and IL-10 gene expression. CONCLUSIONS: Compared with isografts, allografts have more obvious changes, such as epithelial damage, fibroproliferation and lymphocytic infiltration. Th1 and Th2 lymphocyte subtypes contribute to the development of obliterative bronchiolitis in heterotopic trachea transplant model of …

A prognostic model for anoikis-related genes in pancreatic cancer.

Anoikis, a distinct form of programmed cell death, is crucial for both organismal development and maintaining tissue equilibrium. Its role extends to the proliferation and progression of cancer cells. This study aimed to establish an anoikis-related prognostic model to predict the prognosis of pancreatic cancer (PC) patients. Gene expression data and patient clinical profiles were sourced from The Cancer Genome Atlas (TCGA-PAAD: Pancreatic Adenocarcinoma) and the International Cancer Genome Consortium (ICGC-PACA: Pancreatic Ductal Adenocarcinoma). Non-cancerous pancreatic tissue gene expressio

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… Filippini D Agosto S Delfino P Immunoevolution of mouse pancreatic organoid isografts from preinvasive to metastatic disease Sci. Rep. 2019 9 1 12286 10.1038/s41598-019-48663-7 31439856 PMC6706454 61. …

Exosome-based miRNA delivery: Transforming cancer treatment with mesenchymal stem cells.

Recently, increasing interest has been in utilizing mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), especially exosomes, as nanocarriers for miRNA delivery in cancer treatment. Due to such characteristics, nanocarriers are specific: biocompatible, low immunogenicity, and capable of spontaneous tumor accumulation. MSC-EVs were loaded with therapeutic miRNAs and minimized their susceptibility to degradation by protecting the miRNA from accessibility to degrading enzymes and providing targeted delivery of the miRNAs to the tumor cells to modulate oncogenic pathways. In vitro and i

MSC-derived extracellular vesicles: Precision miRNA delivery for overcoming cancer therapy resistance.

Cancer remains a prominent worldwide health concern, presenting existing therapies with frequent difficulties, including major toxicity, limited effectiveness, and treatment resistance emergence. These issues highlight the necessity for novel and enhanced remedies. Exosomes, tiny extracellular vesicles that facilitate intercellular communication, have attracted interest for their potential medicinal applications. Carrying a variety of molecules, including microRNAs, small interfering RNAs, long non-coding RNAs, proteins, lipids, and DNA, these vesicles are positioned as promising cancer treatm

Purinergic Signalling: Therapeutic Developments.

Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990's when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and the

34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 2 : National Harbor, MD, USA. 10 November 2019.

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