scholarly journals Morphological and Functional Studies on Submucosal Islet Transplants in Normal and Diabetic Hamsters

2002 ◽  
Vol 11 (6) ◽  
pp. 529-537 ◽  
Author(s):  
Nikolay Tchervenivanov ◽  
Songyang Yuan ◽  
Mark Lipsett ◽  
Despina Agapitos ◽  
Lawrence Rosenberg
Keyword(s):  
Positive Impact ◽  
Large Animal Model ◽  
Large Animal ◽  
Islet Function ◽  
Term Outcome ◽  
Intravenous Glucose ◽  
K Value ◽  
Long Term Outcome ◽  
Islet Transplants

The long-term outcome of human islet allotransplantation is poor, and it remains to be seen if the Edmonton Protocol will make a positive impact upon the extension of posttransplant islet function. Hence, establishing an implantation site capable of sustaining islet allografts for a prolonged duration needs to be explored. In this study we investigated the submucosal space of the duodenum in Syrian golden hamsters. Following transplantation of more than 800 islets into streptozotocin (STZ)-induced diabetic hamsters, basal nonfasted blood glucose levels decreased from 403 ± 14 to 143 ± 10 mg/dl within 5 weeks posttransplantation. In these animals, in vivo islet function, as determined by intravenous glucose tolerance test (IVGTT), was similar to nondiabetic controls (K values: 1.16 ± 0.12 vs. 0.95 ± 0.06, respectively) and was significantly greater than diabetic controls (K value: 0.47 ± 0.07). Islets transplanted into the submucosal space become richly vascularized within 2 weeks, and there is minimal host inflammatory infiltrate. The β-cells of the graft remain well granulated with insulin for at least 129 days. We conclude that the submucosal space is an effective engraftment site for islets that warrants further development in a large-animal model.

Lugol Iodine Staining Test in Early Detection of Head and Neck Cancer

2017 ◽  
Vol 68 (8) ◽  
pp. 1944-1945
Author(s):  
Catalin Stefan ◽  
Gabriel Lostun ◽  
Alexandra Lostun
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Iodine Staining ◽  
Examination Techniques ◽  
Staining Techniques ◽  
Malignant Lesions

Head and neck cancer represents 3% of malignancies, and it is associated with high mortality due to advanced stage diagnosis. In early stages, the symptomatology can either be absent or be very common, misleading the patient who often ignores it. Early diagnosis of head and neck neoplasia is essential for a favorable long-term outcome. Lately new in vivo examination techniques were developed, and older ones have been improved. Today, in vivo staining techniques are an important tool in the diagnostic of head and neck cancer. Lugol iodine staining method provides valuable information concerning the tumor, allowing the surgeon to differentiate premalignant and malignant lesions.

scholarly journals A patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ling Li ◽  
Mohamad I. Itani ◽  
Kevan J. Salimian ◽  
Yue Li ◽  
Olaya Brewer Gutierrez ◽  
...  
Keyword(s):  
Argon Plasma Coagulation ◽  
Argon Plasma ◽  
Large Animal Model ◽  
Swine Model ◽  
Large Animal ◽  
High Grade ◽  
Gi Tract ◽  
Endoscopic Techniques ◽  
Approved Drugs

AbstractGastrointestinal (GI) strictures are difficult to treat in a variety of disease processes. Currently, there are no Food and Drug Administration (FDA) approved drugs for fibrosis in the GI tract. One of the limitations to developing anti-fibrotic drugs has been the lack of a reproducible, relatively inexpensive, large animal model of fibrosis-driven luminal stricture. This study aimed to evaluate the feasibility of creating a model of luminal GI tract strictures. Argon plasma coagulation (APC) was applied circumferentially in porcine esophagi in vivo. Follow-up endoscopy (EGD) was performed at day 14 after the APC procedure. We noted high grade, benign esophageal strictures (n = 8). All 8 strictures resembled luminal GI fibrotic strictures in humans. These strictures were characterized, and then successfully dilated. A repeat EGD was performed at day 28 after the APC procedure and found evidence of recurrent, high grade, fibrotic, strictures at all 8 locations in all pigs. Pigs were sacrificed and gross and histologic analyses performed. Histologic examination showed extensive fibrosis, with significant collagen deposition in the lamina propria and submucosa, as well as extensive inflammatory infiltrates within the strictures. In conclusion, we report a porcine model of luminal GI fibrotic stricture that has the potential to assist with developing novel anti-fibrotic therapies as well as endoscopic techniques to address recurring fibrotic strictures in humans.

scholarly journals Niobium Carbide Loaded by Macrophage for Targeted Phototherapy Ablation of Breast Cancer

2020 ◽  
Author(s):  
Chiara Da Pieve ◽  
Gabriela Kramer Marek ◽  
Jolanta Saczko ◽  
Anant Shah ◽  
Florian Raes
Keyword(s):  
Animal Study ◽  
Human Body ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Niobium Carbide ◽  
Reactive Oxygen Species Generation ◽  
Large Animal Model ◽  
Large Animal ◽  
Photodynamic Effect

ABSTRACTAltough nanomaterial-mediated phototherapy has been extensively studied, the major antitumor success is limited to treating subcutaneous tumor on nude, lacking of clinically-relevant big animal study. Therefore, it is urgent to make further investigation on the typical big model, which is more closely related to the human body. In this work, niobium carbide (NbC) was selected as photoactive substance in virtue of its outstanding near infrared (NIR) absorption properties and resultantly NIR-triggered hyperthemia and reactive oxygen species generation for the synergetic photothermal and photodynamic effect. Moreover, macrophage was used as bio-carrier for the targeted delivery of NbC and the phagocytosis of macrophages was proved to be able to retain the photothermal/photodynamic effect of NbC. Resultantly, macrophage loaded NbC could realize complete removal of solid tumor on both of nude mice and big animal of rabbits. Meanwhile, two-dimensional ultrasound, shave wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) have been applied for monitoring the physiological evolutions of in vivo tumor post treatment, which clearly disclosed the photoablation process of tumor and provided a new way for the surveillance of tumor on the big animal study. Hence, large animal model study in this work presented higher clinical significance than the previous studies.SignificanceFindings show that niobium carbide carried by macrophages can be used for targeted phototherapy. At the same time, we applied the rabbit tumor model which is closer to the human body microenvironment.

scholarly journals Intracoronary Delivery of Porcine Cardiac Progenitor Cells Overexpressing IGF-1 and HGF in a Pig Model of Sub-Acute Myocardial Infarction

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2571
Author(s):  
Cristina Prat-Vidal ◽  
Verónica Crisóstomo ◽  
Isabel Moscoso ◽  
Claudia Báez-Díaz ◽  
Virginia Blanco-Blázquez ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Growth Factor ◽  
Progenitor Cells ◽  
Large Animal Model ◽  
Cardiac Progenitor Cells ◽  
Large Animal ◽  
Insulin Growth Factor ◽  
Decellularized Extracellular Matrix ◽  
Preclinical Animal Models

Human cardiac progenitor cells (hCPC) are considered a good candidate in cell therapy for ischemic heart disease, demonstrating capacity to improve functional recovery after myocardial infarction (MI), both in small and large preclinical animal models. However, improvements are required in terms of cell engraftment and efficacy. Based on previously published reports, insulin-growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) have demonstrated substantial cardioprotective, repair and regeneration activities, so they are good candidates to be evaluated in large animal model of MI. We have validated porcine cardiac progenitor cells (pCPC) and lentiviral vectors to overexpress IGF-1 (co-expressing eGFP) and HGF (co-expressing mCherry). pCPC were transduced and IGF1-eGFPpos and HGF-mCherrypos populations were purified by cell sorting and further expanded. Overexpression of IGF-1 has a limited impact on pCPC expression profile, whereas results indicated that pCPC-HGF-mCherry cultures could be counter selecting high expresser cells. In addition, pCPC-IGF1-eGFP showed a higher cardiogenic response, evaluated in co-cultures with decellularized extracellular matrix, compared with native pCPC or pCPC-HGF-mCherry. In vivo intracoronary co-administration of pCPC-IGF1-eGFP and pCPC-HFG-mCherry (1:1; 40 × 106/animal), one week after the induction of an MI model in swine, revealed no significant improvement in cardiac function.

A novel in vivo large animal model of lumbar spinal joint degeneration

2018 ◽  
Vol 18 (10) ◽  
pp. 1896-1909 ◽  
Author(s):  
Tian Wang ◽  
Matthew H. Pelletier ◽  
Chris Christou ◽  
Rema Oliver ◽  
Ralph J. Mobbs ◽  
...  
Keyword(s):  
Animal Model ◽  
Large Animal Model ◽  
Large Animal ◽  
Joint Degeneration ◽  
Lumbar Spinal

scholarly journals Autologous transplantation of canine long-term marrow culture cells genetically marked by retroviral vectors

Blood ◽  
1992 ◽  
Vol 79 (2) ◽  
pp. 356-364 ◽  
Author(s):  
RF Carter ◽  
AC Abrams-Ogg ◽  
JE Dick ◽  
SA Kruth ◽  
VE Valli ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Autologous Transplantation ◽  
Large Animal Model ◽  
Multiple Infections ◽  
Large Animal ◽  
Retroviral Infection ◽  
Hematopoietic Stem ◽  
Marrow Cells

Abstract Retroviral infection of bone marrow cells in long-term marrow cultures (LTMCs) offers several theoretical advantages over other methods for gene transfer into hematopoietic stem cells. To investigate the feasibility of this approach in a large animal model system, we subjected LTMCs from nine dogs to multiple infections with retrovirus containing the neomycin phosphotransferase gene (neo) during 21 days of culture. Feeder layers, cocultivation, polycations, and selection were not used. The in vitro gene transfer efficiency was 70% as determined by polymerase chain reaction amplification of neo sequences in colony- forming unit granulocyte-macrophage (CFU-GM) obtained from day-21 LTMCs. Day-21 LTMC cells were infused into autologous recipients with (four dogs) and without (three dogs) marrow-ablative conditioning. At 3 months posttransplant, up to 10% of marrow cells contained the neo gene. This percentage declined to 0.1% to 1% at 10 to 21 months posttransplant. Neo was also detected in individual CFU-GM, burst- forming unit-erythroid (BFU-E), and CFU-Mix progenitors derived from marrow up to 21 months postinfusion and in cultures of peripheral blood- derived T cells up to 19 months postinfusion. There was no difference in the percentage of neo-marked cells present when dogs that received marrow ablative conditioning were compared with dogs receiving no conditioning. Detection of neo-marked marrow cells almost 2 years after autologous transplantation in a large mammalian species shows that retroviral infection of marrow cells in LTMCs is a potentially nontoxic and efficient protocol for gene transfer. Further, our results suggest that marrow conditioning and in vivo selection pressure to retain transplanted cells may not be absolute requirements for the retention of genetically marked cells in vivo.

scholarly journals Light-degradable hydrogels as dynamic triggers for gastrointestinal applications

2020 ◽  
Vol 6 (3) ◽  
pp. eaay0065 ◽  
Author(s):  
Ritu Raman ◽  
Tiffany Hua ◽  
Declan Gwynne ◽  
Joy Collins ◽  
Siddartha Tamang ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Implantable Devices ◽  
Large Animal Model ◽  
Large Animal ◽  
Gi Tract ◽  
Biomedical Device ◽  
Precise Tool ◽  
And Performance

Triggerable materials capable of being degraded by selective stimuli stand to transform our capacity to precisely control biomedical device activity and performance while reducing the need for invasive interventions. Here, we describe the development of a modular and tunable light-triggerable hydrogel system capable of interfacing with implantable devices. We apply these materials to two applications in the gastrointestinal (GI) tract: a bariatric balloon and an esophageal stent. We demonstrate biocompatibility and on-demand triggering of the material in vitro, ex vivo, and in vivo. Moreover, we characterize performance of the system in a porcine large animal model with an accompanying ingestible LED. Light-triggerable hydrogels have the potential to be applied broadly throughout the GI tract and other anatomic areas. By demonstrating the first use of light-degradable hydrogels in vivo, we provide biomedical engineers and clinicians with a previously unavailable, safe, dynamically deliverable, and precise tool to design dynamically actuated implantable devices.

scholarly journals Successful treatment of canine hemophilia by continuous expression of canine FVIIa

Blood ◽  
2009 ◽  
Vol 113 (16) ◽  
pp. 3682-3689 ◽  
Author(s):  
Paris Margaritis ◽  
Elise Roy ◽  
Majed N. Aljamali ◽  
Harre D. Downey ◽  
Urs Giger ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Hemophilia A ◽  
Viral Vector ◽  
Canine Model ◽  
Factor Vii ◽  
Large Animal Model ◽  
Large Animal ◽  
Spontaneous Bleeding ◽  
Human Factor Viii

Abstract Continuous expression of activated factor VII (FVIIa) via gene transfer is a potential therapeutic approach for hemophilia patients with or without inhibitory antibodies to human factor VIII (FVIII) or IX (FIX). Here, we investigate whether gene transfer of an engineered canine FVIIa (cFVIIa) transgene can affect hemostasis in a canine model of hemophilia, a good predictor of efficacy of hemophilia treatments. Purified recombinant cFVIIa exhibited 12-fold higher tissue factor–dependent activity than purified recombinant zymogen cFVII. Subsequently, we generated a serotype 8 recombinant adeno-associated viral vector expressing cFVIIa from a liver-specific promoter. Vector delivery via the portal vein in hemophilia A and B dogs was well tolerated, and long-term expression of cFVIIa resulted in a shortening of the prothrombin time, partial correction of the whole blood clotting time and thromboelastography parameters, and a complete absence of spontaneous bleeding episodes. No evidence of hepatotoxicity, thrombotic complications, or inhibitory immune response was found. These data provide the first evidence for in vivo efficacy and safety of continuously expressed FVIIa as a FVIII/FIX-bypassing agent in a large animal model of hemophilia, avoiding the risk of inhibitor formation associated with bolus FVIII or FIX infusion.

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