3 results on '"Pownder, Sarah L."'
Search Results
2. Integrin α10β1-Selected Mesenchymal Stem Cells Mitigate the Progression of Osteoarthritis in an Equine Talar Impact Model.
- Author
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Delco, Michelle L., Goodale, Margaret, Talts, Jan F., Pownder, Sarah L., Koff, Matthew F., Miller, Andrew D., Nixon, Bridgette, Bonassar, Lawrence J., Lundgren-Åkerlund, Evy, and Fortier, Lisa A.
- Subjects
ANKLEBONE injuries ,ARTICULAR cartilage injuries ,ANIMAL experimentation ,ARTHROSCOPY ,BIOLOGICAL models ,CELL receptors ,COLLAGEN ,ENZYME-linked immunosorbent assay ,GLYCOSAMINOGLYCANS ,HOMEOSTASIS ,HORSES ,IMMUNOHISTOCHEMISTRY ,LABORATORIES ,MAGNETIC resonance imaging ,OSTEOARTHRITIS ,PROSTAGLANDINS ,PROTEINS ,REGENERATION (Biology) ,STATISTICS ,STEM cells ,SYNOVIAL fluid ,SYNOVIAL membranes ,T-test (Statistics) ,TUMOR necrosis factors ,WOUNDS & injuries ,CYTOMETRY ,DATA analysis ,REPEATED measures design ,DISEASE progression ,DATA analysis software ,DESCRIPTIVE statistics - Abstract
Background: Early intervention with mesenchymal stem cells (MSCs) after articular trauma has the potential to limit progression of focal lesions and prevent ongoing cartilage degeneration by modulating the joint environment and/or contributing to repair. Integrin α10β1 is the main collagen type II binding receptor on chondrocytes, and MSCs that are selected for high expression of the α10 subunit have improved chondrogenic potential. The ability of α10β1-selected (integrin α10
high ) MSCs to protect cartilage after injury has not been investigated. Purpose: To investigate integrin α10high MSCs to prevent posttraumatic osteoarthritis in an equine model of impact-induced talar injury. Study Design: Controlled laboratory study. Methods: Focal cartilage injuries were created on the tali of horses (2-5 years, n = 8) by using an impacting device equipped to measure impact stress. Joints were treated with 20 × 106 allogenic adipose-derived α10high MSCs or saline vehicle (control) 4 days after injury. Synovial fluid was collected serially and analyzed for protein content, cell counts, markers of inflammation (prostaglandin E2, tumor necrosis factor α) and collagen homeostasis (procollagen II C-propeptide, collagen type II cleavage product), and glycosaminoglycan content. Second-look arthroscopy was performed at 6 weeks, and horses were euthanized at 6 months. Joints were imaged with radiographs and quantitative 3-T magnetic resonance imaging. Postmortem examinations were performed, and India ink was applied to the talar articular surface to identify areas of cartilage fibrillation. Synovial membrane and osteochondral histology was performed, and immunohistochemistry was used to assess type I and II collagen and lubricin. A mixed effect model with Tukey post hoc and linear contrasts or paired t tests were used, as appropriate. Results: Integrin α10high MSC-treated joints had less subchondral bone sclerosis on radiographs (P =.04) and histology (P =.006) and less cartilage fibrillation (P =.04) as compared with control joints. On gross pathology, less India ink adhered to impact sites in treated joints than in controls, which may be explained by the finding of more prominent lubricin immunostaining in treated joints. Prostaglandin E2 concentration in synovial fluid and mononuclear cell synovial infiltrate were increased in treated joints, suggesting possible immunomodulation by integrin α10high MSCs. Conclusion: Intra-articular administration of integrin α10high MSCs is safe, and evidence suggests that the cells mitigate the effects of joint trauma. Clinical Relevance: This preclinical study indicates that intra-articular therapy with integrin α10high MSCs after joint trauma may be protective against posttraumatic osteoarthritis. [ABSTRACT FROM AUTHOR]- Published
- 2020
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3. BioCartilage Improves Cartilage Repair Compared With Microfracture Alone in an Equine Model of Full-Thickness Cartilage Loss.
- Author
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Fortier, Lisa A., Chapman, Hannah S., Pownder, Sarah L., Roller, Brandon L., Cross, Jessica A., Cook, James L., and Cole, Brian J.
- Subjects
CARTILAGE regeneration ,ARTICULAR cartilage ,KNEE injuries ,PLATELET-rich plasma ,ANIMAL experimentation ,BIOMEDICAL materials ,HORSES ,PLASTIC surgery ,ARTICULAR cartilage injuries ,TREATMENT effectiveness ,DESCRIPTIVE statistics ,IN vitro studies - Abstract
Background: Microfracture (MFx) remains a dominant treatment strategy for symptomatic articular cartilage defects. Biologic scaffold adjuncts, such as particulated allograft articular cartilage (BioCartilage) combined with platelet-rich plasma (PRP), offer promise in improving clinical outcomes as an adjunct to MFx. Purpose: To evaluate the safety, biocompatibility, and efficacy of BioCartilage and PRP for cartilage repair in a preclinical equine model of full-thickness articular cartilage loss. Study Design: Controlled laboratory study. Methods: Two 10-mm-diameter full-thickness cartilage defects were created in 5 horses in the trochlear ridge of both knees: one proximal (high load) and another distal (low load). Complete blood counts were performed on each peripheral blood and resultant PRP sample. In each horse, one knee received MFx with BioCartilage + PRP, and the other knee received MFx alone. Horses were euthanized at 13 months. Outcomes were assessed with serial arthroscopy, magnetic resonance imaging (MRI), micro–computed tomography (micro-CT), and histology. Statistics were performed using a mixed-effects model with response variable contrasts. Results: No complications occurred. PRP generated in all subjects yielded an increase in platelet fold of 3.8 ± 4.7. Leukocyte concentration decreased in PRP samples by an average fold change of 5 ± 0.1. The overall International Cartilage Repair Society repair score in both the proximal and distal defects was significantly higher (better) in the BioCartilage group compared with MFx (proximal BioCartilage: 7.4 ± 0.51, MFx 4.8 ± 0.1, P = .041; distal BioCartilage: 5.6 ± 0.98, MFx 2.6 ± 1.5, P = .022). BioCartilage-treated proximal defects demonstrated improved histologic scores for repair-host integration (BioCartilage, 96 ± 9; MFx, 68 ± 18; P = .02), base integration (BioCartilage, 100 ± 0; MFx, 70 ± 37; P = .04), and formation of collagen type II (BioCartilage, 82 ± 8; MFx, 58 ± 11; P = .05) compared with the positive control. On MRI, T2 relaxation time was significantly shorter (better) in the superficial region of BioCartilage-treated distal defects compared with MFx (P = .05). There were no significant differences between BioCartilage and MFx on micro-CT analysis. Conclusion: BioCartilage with PRP safely improved cartilage repair compared with MFx alone in an equine model of articular cartilage defects up to 13 months after implantation. Clinical Relevance: The 1-year results of BioCartilage + PRP suggest that homologous allograft tissue provides a safe and effective augmentation of traditional MFx. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
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