Quantification of histomorphometric and structural bone changes in a sheep model for fracture treatment in osteoporotic bone

2003 ◽  
Vol 16 (04) ◽  
pp. 243-249 ◽  
Author(s):  
E. Winterstein ◽  
C. Eckhardt ◽  
B. Rahn ◽  
J. Goldhahn ◽  
E. Schneider ◽  
...  
Keyword(s):  
Iliac Crest ◽  
Structural Parameters ◽  
Large Animal Model ◽  
Control Group ◽  
Osteoporotic Bone ◽  
Fracture Treatment ◽  
Large Animal ◽  
Average Dose ◽  
Sheep Model ◽  
Trabecular Thickness

SummaryThe histomorphometrical cancellous bone parameters of osteoporotic ewes were examined to establish a large animal model for the investigation of fracture treatment and healing in osteoporotic bone. Eighteen animals were divided into 2 groups. Group 1 (n = 8, age 3 to 5 years) served as an untreated control. In Group 2 (n = 10, age 7 to 9 years) osteoporosis was induced by means of ovariectomy, methylprednisolone application (average dose 160 mg/week) and Ca./Vit.D restricted diet during 7 months. Biopsies from iliac crest, femoral head and lumbar spine were harvested. Structural parameters from the biopsies were determined using μCT. In order to investigate static and dynamic parameters of bone remodelling, undecalcified sections were digitized and evaluated by means of image analysing software. Morphologically, bone area and trabecular thickness were reduced in osteoporotic sheep. Bone perimeter (−20%), trabecular number (−16%) and separation (+39%) showed a significant change in the iliac crest. The structure model index indicated a shift from the plate-to the rodmodel. At different skeletal sites of osteoporotic sheep bone resorption was significantly increased (250-675%), and bone formation significantly decreased (77-89%). Osteoid thickness (O.Th) was reduced (28-62%). In osteoporotic sheep the mean length of single labels was significantly shortened (64-73%) and the mineralising surface showed a significant decrease (80-92%). The mineralisation of the osteoid was comparable to the control group. The histomorphometrical changes in this sheep model of osteoporosis are comparable to the human situation of a combined post-menopausal and steroid-induced osteoporosis.

End-to-side nerve repair in a large animal model: how does it compare with conventional methods of nerve repair?

2012 ◽  
Vol 38 (2) ◽  
pp. 192-202 ◽  
Author(s):  
S. J. A. Kettle ◽  
N. E. Starritt ◽  
M. A. Glasby ◽  
T. E. J. Hems
Keyword(s):  
Nerve Regeneration ◽  
Functional Outcomes ◽  
Axon Regeneration ◽  
Nerve Repair ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
Salvage Procedure ◽  
Clinical Tool ◽  
Sheep Model

A large animal (sheep) model was used to compare nerve axon regeneration and return of muscle function after a median-to-ulnar nerve end-to-side neurorrhaphy technique with conventional, clinically established, methods of nerve repair and untreated controls. Three groups of sheep were allocated to end-to-side repair (12 animals), a conventional method of nerve repair (18 animals), or a control group (eight animals). After a year nerve repairs were assessed electrophysiologically and histologically, and the muscles supplied by the repaired nerves were assessed physiologically. There were no significant differences in the outcomes of nerve repair between different conventional techniques. Half of the end-to-side nerve repairs supported nerve regeneration. The functional outcomes of the end-to-side repairs were inferior to conventional techniques which were, in turn, inferior to controls. End-to-side neurorrhaphy supported nerve regeneration, but the reliability of this technique is called into question and its use as a clinical tool can only be recommended as a salvage procedure.

Abstract 657: A New Translational Model of Hypercholesterolemia and Atherosclerosis: Effect of Statins on LDLR KO Miniature Swine

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Dale E Mais ◽  
Thomas Vihtelic ◽  
Chidozie Amuzie ◽  
Steven Denham ◽  
John R Swart ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Clinical Chemistry ◽  
Small Animal ◽  
Normal Diet ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
Wild Type ◽  
High Fat ◽  
Miniature Swine

Small animal models of atherosclerosis are commonly used in drug studies; however, the results often fail to translate into the clinic. A large animal model that more accurately reflects the human disease is needed. We recently developed a transgenic Yucatan pig model in which the LDL receptor (LDLR) gene is knocked out. Five groups of Yucatan pigs (N=4 per group), either wild type (LDLR+/+) or heterozygote (LDLR+/-) were fed a normal diet or a high fat diet for a six month period. One of the heterozygote/high fat diet groups in addition received a daily dose of a statin (atorvastatin) at 3 mg/kg. Every two weeks during the study a variety of clinical chemistry parameters were measured. At study termination, select arteries were collected, stained for lipid deposits and quantitated. In addition, sections of these arteries were prepared for immunohistochemistry to detect selected markers of macrophage infiltration into the atherosclerotic plaques. As expected, pigs fed a high fat diet gained significantly more weight at six months whether they were wild type or LDLR+/-. Atorvastatin appeared to attenuate this weight gain. There were significant increases in total cholesterol, HDL and LDL in pigs fed the high fat diet compared to their corresponding control group. The group receiving the atorvastatin had reduced values of these parameters compared to controls showing that a statin had a beneficial effect on lipid levels even in a high fat diet scenario. VLDL levels were not affected but there were triglyceride changes across the groups. Liver function was unchanged based on total bilirubin and AST while ALT measurements were altered in some of the groups. Immunohistochemistry and histomorphometry was performed on some arteries. Atorvastatin-induced amelioration of hypercholesterolemia in this model underscores its translational utility.

Percutaneous Intramyocardial Septal Radiofrequency Ablation for Interventricular Septal Reduction: An Ovine Model with 1-Year Outcomes

Cardiology ◽  
2019 ◽  
Vol 145 (1) ◽  
pp. 53-62
Author(s):  
Fang Liu ◽  
Jianli Fu ◽  
David Hsi ◽  
Chao Sun ◽  
Guangbin He ◽  
...  
Keyword(s):  
Radiofrequency Ablation ◽  
Sham Group ◽  
Normal Sinus Rhythm ◽  
Interventricular Septum ◽  
Large Animal Model ◽  
Lv Function ◽  
Wall Thickening ◽  
Large Animal ◽  
Sheep Model

Background: Percutaneous intramyocardial (PIM) septal radiofrequency ablation (SRA) is a novel treatment approach for hypertrophic obstructive cardiomyopathy patients, but there has been lack of a large animal model to study PIM-SRA. We aimed to validate the long-term safety and efficacy of PIM-SRA and to observe pathological changes of the ablated interventricular septum (IVS) in a healthy sheep model. Methods and Results: Twelve sheep were randomized to the PIM-SRA group (n = 6) and the sham group (n = 6). In the PIM-SRA group, a radiofrequency (RF) electrode was inserted into the IVS with a maximum power of 80 W for 5 min. In the sham group, the RF electrode tip was positioned in the IVS segment but without RF power delivery. Septal hypokinesis was seen in all PIM-SRA group animals immediately after the procedure; the systolic wall thickening rate and motion amplitude of the ablated region decreased (p < 0.01), and the diastolic IVS thickness also decreased significantly over time (p < 0.01). ECG showed that all the sheep had normal sinus rhythm during the follow-up. Pathological examinations revealed scar tissue in the ablated region as expected. Conclusions: PIM-SRA produced precisely ablated myocardial tissue, reduced the IVS thickness significantly, preserved the global LV function, and avoided the incidence of conduction system damage in the long term. PIM-SRA was found to be a safe and effective minimally invasive septal reduction therapy.

Ex Vivo Expanded T Regulatory (Treg) Cells Block Conversion of Mixed Chimeras To Complete Donor Chimerism.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5168-5168
Author(s):  
Marina Lesnikova ◽  
Alla Nikitine ◽  
Nicola Mason ◽  
Richard A. Nash ◽  
George E. Georges
Keyword(s):  
T Cells ◽  
Ex Vivo ◽  
Treg Cells ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
Not Given ◽  
Tolerance Mechanism ◽  
Donor Chimerism ◽  
Mixed Chimeras

Abstract A highly effective method to establish long-term, stable mixed hematopoietic chimerism was developed in the dog model. This involves nonmyeloablative allogeneic hematopoietic cell transplantation (HCT), consisting of 2 Gray (Gy) total body irradiation (TBI), dog leukocyte antigen (DLA)-identical marrow, and short-term post-grafting immunosuppression. We hypothesized that CD4+CD25+ Treg cells may be important regulators for the maintenance of cellular immune tolerance after allogeneic HCT. Previously, we showed in 8 mixed chimeras that naive donor lymphocyte infusion (DLI) did not change the level of donor chimerism. However, reconditioning mixed chimeras with 2 Gy TBI followed by DLI “breaks” tolerance and increases the level of donor chimerism. Seven mixed chimeras were reconditioned with 2 Gy TBI followed by DLI. Within 4 weeks after DLI, conversion to 100% donor chimerism was seen in 5 of 7 dogs and 2 dogs had a > 50% sustained increase in donor chimerism. Four recipients developed graft-versus host disease (GVHD). A control group of 3 mixed chimeras reconditioned with 2 Gy TBI without DLI had no change in donor chimerism. These results suggest that reconditioning with 2 Gy TBI followed by DLI can break the tolerance mechanism established in mixed chimeras. Next we asked if CD4+CD25+ Treg cells obtained from mixed chimeras before reconditioning could block the increase in donor chimerism following 2 Gy TBI and DLI. Peripheral blood mononuclear cells (PBMC) from 8 mixed chimeras were obtained by leukapheresis and cultured in bulk mixed leukocyte culture (MLC) with 3rd party DLA-mismatched, unrelated and irradiated CD34+ derived dendritic cells (10:1 responder: stimulator ratio) or PBMC (1:1). On day 4 of MLC, CD25+ cells were isolated by positive immunomagnetic selection. Next, artificial antigen presenting cells (aAPC, KT32) were added to expand the CD4+CD25+ Treg cells. The aAPC expressed Fcγ receptor CD32, canine CD86, and human IL-15, were loaded with the canine-specific mitogenic anti-CD3ε antibody 17.6F9 and irradiated prior to stimulation of CD4+CD25+ Treg. After 7 days, Treg were expanded a median of 23 (range, 8–36)-fold. Expanded CD4+CD25+ Treg were assessed for phenotype and in vitro function. The Treg cells were generated from 8 mixed chimeras and were infused back into the respective dogs (median dose 1× 107/kg) after reconditioning with 2 Gy TBI and immediately prior to DLI. In 6 of 8 dogs there was no change in the level of donor chimerism at 16–20 weeks follow-up; 2 dogs converted to complete donor chimerism within 6 weeks. Treatment with expanded Treg cells blocked conversion to complete donor chimerism after 2 Gy TBI +DLI in 6 of 8 dogs, compared with significant increases in donor chimerism for all 7 dogs after 2 Gy TBI +DLI not given Treg (p=.007). None of the 8 Treg recipient dogs developed GVHD, compared with 4 of 7 not given Treg, (p=0.02). A control group of 4 mixed chimeras were infused with expanded, non-Treg CD25− T cells. To this end, CD25+ T cells were immunomagneticaly depleted on day 4 of MLC. CD25− T cells were expanded with aAPC. Three of 4 dogs converted to the complete donor chimerism within 7 weeks after 2 Gy TBI, non-Treg and DLI. These results suggest that ex vivo expanded CD4+CD25+ Treg cells have in vivo function in a large animal model and can restore the tolerance mechanism in mixed chimeras that is broken by 2 Gy TBI and DLI.

Sheep Model for Fracture Treatment in Osteoporotic Bone: A Pilot Study About Different Induction Regimens

2000 ◽  
Vol 14 (8) ◽  
pp. 559-565 ◽  
Author(s):  
Christoph Alexander Lill ◽  
Alexa Katrin Fluegel ◽  
Erich Schneider
Keyword(s):  
Pilot Study ◽  
Osteoporotic Bone ◽  
Fracture Treatment ◽  
Sheep Model

scholarly journals Establishment of Type 2 Diabetes Mellitus Models Using High-Fat Diet and STZ in Bama Minipigs

2021 ◽  
Author(s):  
Yuqiong Zhao ◽  
Miaomiao Niu ◽  
Jia Yunxiao ◽  
Yuan Jifang ◽  
Xiang Lei ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Low Dose ◽  
Normal Diet ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
High Cholesterol ◽  
High Fat ◽  
Accelerated Atherosclerosis ◽  
Atherosclerotic Lesions

Abstract BackgroundIn the past 20 years, the number of adults with diabetes has tripled. For most of the researches are often conducted in rodent T2DM models, and effective drugs developed have low clinical conversion efficiency. Therefore, it is urgent to establish a large animal model to explore the pathogenesis of T2DM and formulate disease prevention and control strategies. MethodsThis study was designed to establish and validate a T2DM model in minipigs with notable hyperglycemia using a high-fat diet and low-dose streptozotocin (STZ)，and examined the influence of STZ infusion time, the difference between a high-fat diet and a high-cholesterol and high-fat diet, and the atherosclerotic lesions accelerated by diabetes. Male Bama minipigs (n=24) were randomly divided into 5 groups; the control group was fed with normal diet for 9 months; STZ+HFD group and STZ+HCFD group were infused with 90 mg/kg STZ and then fed with a high-fat diet or high-cholesterol and high-fat diet for 9 months, respectively; HFD + STZ group and HCFD + STZ group were fed with a high-fat diet or high-cholesterol and high-fat diet, respectively, for nine months (after 3 months, pigs were injected with 90 mg/kg STZ intravenously). ResultsThe results showed the serum glucose concentrations were within the normal range in all groups except for HFD + STZ group and HCFD + STZ group. Animals fed with a high-fat diet for 9 months, did not develop apparent atherosclerotic lesions; nevertheless, atherosclerotic lesions were seen in animals fed with high-cholesterol and high-fat diets. Moreover, hyperglycemia accelerated atherosclerosis (lesions on the intimal surface of the abdominal aorta, 0.44±0.29 vs. 0.28±0.26) in minipigs. ConclusionsHigh-fat/high-cholesterol and high-fat diet combined with low-dose streptozotocin successfully established T2DM in minipigs. High-fat diet could not induce apparent atherosclerosis lesions but high-cholesterol and high-fat diet could during the nine months period. Hyperglycemia accelerated atherosclerosis in the minipigs.

A sheep model for fracture treatment in osteoporotic bone

1999 ◽  
Vol 13 (4) ◽  
pp. 298-299
Author(s):  
E Schneider ◽  
C Lill ◽  
A Flügel
Keyword(s):  
Osteoporotic Bone ◽  
Fracture Treatment ◽  
Sheep Model

274 POTENTIAL OF BOVINE MARROW STROMAL CELLS CULTURED AT DIFFERENT PASSAGES TO DIFFERENTIATE INTO ADIPOCYTE-LIKE CELLS

2009 ◽  
Vol 21 (1) ◽  
pp. 234
Author(s):  
J. W. Feng ◽  
X. J. Bai ◽  
J. Zhao ◽  
M. Murakami ◽  
Y. J. Dong
Keyword(s):  
Stromal Cells ◽  
Horse Serum ◽  
Marrow Stromal Cells ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
Differentiation Potential ◽  
Base Medium ◽  
Adipocytic Differentiation ◽  
Oil Red O

Bovine marrow stromal cells (MSC) would serve as a preclinical large-animal model for investigating the use of the adult pluripotent cells MSC for human cell therapies, but the information is limited. In this study, adipocytic differentiation was examined in bovine MSC at different passages (psg) after various adipogenic treatments, as the first step in characterizing the multilineage differentiation potential during an extensive culture. Bovine MSC were cultured from the femurs of 3-month-old Holstein calves using a previously described method with slight modifications (Xiang et al. 2001 Chin. J. Pathophysiol. 17, 598–601). The MSC at psg 2, 5, 10, 15, and 20 (total cell culture periods of 10, 19, 34, 49, and 64 days, respectively, 4 × 103 cells cm–2) were cultured for 2 days post-psg. Previously, we found that most of mouse MSC became adipocyte-like cells after they were cultured with a base medium (DMEM, 4.5 g L–1 glucose, plus 10% FBS) containing horse serum (HS) for 5 weeks. Therefore, the bovine MSC at each psg (70% confluence) were then cultured in the base medium containing 0.1 μm dexamethasone, 0.1 mm 3-isobutyl-1-methylxanthine, 0.2 mm indomethacin, and 10 μg mL–1 insulin [hormonal-mixture (HM) group], the base medium containing 15% HS (HS group), or the base medium (control group) for adipogenic induction. The cells were stained with oil red O after being cultured in the respective medium for 1, 3, or 5 weeks. In this study, all cells containing oil red O-stained lipid droplets (LD) were counted as ‘oil red O-positive (OP) cells’, regardless of the size and number contained. The rate of OP cells in each group was determined as follows. In the dishes, the total number of cells (60 to 100 cells) and OP cell number were counted in a randomly selected microscopic field (200×), and the rate of OP cells was calculated. A total of 10 random fields of view were examined, and the mean value was obtained for each group. Data were analyzed by ANOVA. In the HM group, OP cells were detectable about Day 7 and were clearly visible by 2 weeks. After 5 weeks, OP cell rates were significantly greater (P < 0.05) in the cells at psg 2 and 5 than in those at psg 10, 15, and 20 (71 and 70% v. 66, 63, and 64%). In the HS group, cytoplasmic LD was detectable about Day 10 and the number increased gradually by 3 weeks. After 5 weeks, OP cell rate was significantly greater (P < 0.05) in the cell at psg 2, 5, and 10 than in those at psg 15 and 20 (53, 57, and 51% v. 47 and 39%). Also, the size and number of LD in each cell tended to be lower in the HS group than in the corresponding HM group. In the control group, 4–5% of the cells were OP after 5 weeks. These results suggest that the ability of bovine MSC to differentiate into adipocyte-like cells decreased after long-term culture, and that horse serum was capable of inducing adipocytic differentiation of bovine MSC in vitro, but its efficacy was less than that of the hormonal mixture. Further studies to detect adipocyte-specific markers, such as G3PDH activity and aP2 expression, from these cells are needed for the quantitative analysis of the differentiation.

scholarly journals Nano-hemostats and a Pilot Study of Their Use in a Large Animal Model of Major Vessel Hemorrhage in Endoscopic Skull Base Surgery

2016 ◽  
Vol 38 (03) ◽  
pp. 215-221
Author(s):  
Jae Murphy ◽  
Sarah Vreugde ◽  
Alkis Psaltis ◽  
P. Wormald ◽  
Alistair Jukes
Keyword(s):  
Pilot Study ◽  
Skull Base ◽  
Skull Base Surgery ◽  
Coagulation Cascade ◽  
Large Animal Model ◽  
Large Animal ◽  
Small Pilot Study ◽  
Sheep Model ◽  
Endoscopic Skull Base Surgery ◽  
Major Vessel

AbstractNano-hemostats are synthetic amino acid chains that self-assemble into a scaffold under certain conditions. These have been shown to be effective in stopping bleeding in small animal models of hemorrhage. Proposed mechanisms for their effect are that they form a mesh analogous to the fibrin plug in native hemostasis and that they may potentiate both platelet activation and the coagulation cascade. These may potentially become valuable adjuncts to endoscopic skull base surgery where there is the potential for both major vessel injury and smaller perforator injury to eloquent areas where bipolar cautery may not be suitable. We present a summary of the clinical studies to date and a small pilot study of nano-hemostat in an endoscopic sheep model of major vessel hemorrhage to determine its efficacy in stopping bleeding in this potentially catastrophic complication.

Abstract TP107: Midline Shift Predicts Functional Outcomes in Porcine Ischemic Stroke Model

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Samantha Spellicy ◽  
Erin Kaiser ◽  
Michael Bowler ◽  
Brian Jurgielewicz ◽  
Robin Webb ◽  
...  
Keyword(s):  
Animal Model ◽  
Ischemic Stroke ◽  
Functional Outcomes ◽  
Randomized Study ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
Midline Shift ◽  
Post Stroke ◽  
Significant Difference

In this study, we sought to identify acute MRI parameters which are predictive of long-term functional outcomes as well as assess the effects of a neural stem cell extracellular vesicle (NSC EV) therapeutic in a large animal model of ischemic stroke. In this randomized study, stroke was induced through a permanent right-sided middle cerebral artery occlusion (MCAO) on 16 male landrace pigs, which were divided into either treatment or control group. NSC EVs or PBS was administered at 2, 14, and 24 hours, and MRI was conducted at day 1 and 84 post-stroke. Data on 65 gait and 25 behavior parameters were collected pre-stroke and at multiple timepoints over 84 days following MCAO. Of all 15 measured MRI parameters, axial and coronal midline shift (MLS), at day 1 post stroke, had the highest total number of significant correlations (52 parameters at p<0.05) to acute and chronic functional measurements in control animals such as step time in the left front limb (p=0.0322) and cycle time in the right hind limb (p=0.0011) respectively. This suggests MLS is the best overall predictor of specific functional deficits at both acute and chronic timepoints, which to our knowledge has never been shown in an animal model. Additionally, the parameters found to be correlated to MLS in control animals were not correlated in NSC EV-treated animals, suggesting NSC EV treatment disrupts this natural correlation between degree of MLS and functional outcomes. NSC EVs and control pigs were binned into either high or low MLS groups and their survival and recovery was assessed by the modified Rankin Scale (mRS). While there was a significant difference in mRS scores of control animals with high and low MLS at day 6 post-MCAO (p=0.0008), there was not in NSC EV-treated animals (p=0.6754). Further, there was a significant difference in survival of control animals with high and low axial MLS (p=0.0401), but not in the NSC EV group (p=0.4142). Additionally, mRNA expression of GFAP was significantly correlated with increasing MLS in non-treated but not NSC EV-treated animals. These findings show although NSC EV treatment does not significantly alter the degree of MLS 1-day post-MCAO, it does alter gene expression, increase survival, and improve functional recovery following large MLS alterations.

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