A12 Dose Dependent Chondroprotective Effects of Allogenic Stro-3+ Mesenchymal Precursor Stem Cells Following Direct Intra-Articular Injection Into Joints of an Ovine Model of Early Osteoarthritis

Read, Roger W.; Cake, Martin; Smith, Tim; Little, Christopher B.; Smith, Margaret M.; Appleyard, Richard; Itescu, Silviu; Ghosh, Peter

doi:10.1016/s1063-4584(08)60058-8

Cited by 2 publications

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“…The receptor engagement results in secretion by the MPCs of prostaglandin E2 and indoleamine 2,3-dioxygenase which can polarise monocytes to an anti-inflammatory M2 phenotype and T helper 17 cells to FoxP3 T regulatory cells [ 14 , 49 ]. This pathway results in increased IL-10 levels and reduction in the very inflammatory cytokines that initiated the response [ 30 , 31 , 50 ]. Moreover, co-culture of human synovial and cartilage explants exposed to conditioned media from MSC pre-treated with TNF-alpha showed reduced expression of IL-beta and matrix metalloproteinases and upregulation of the cytokine signalling suppressor 1 gene while, in cartilage, upregulation of IL-1 receptor antagonist and downregulation of the proteoglycan degrading proteinase ADAMTS-5 was observed [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…Our previous preclinical studies using ovine models of post-traumatic OA [ 30 ] and collagen-induced arthritis [ 31 , 32 ] have demonstrated the safety and efficacy of allogeneic STRO-3 + -selected MPCs in preserving synovial joint articular cartilage, downregulating pro-inflammatory cytokine activities, and preserving cartilage and endothelial cell function. These encouraging preclinical findings using allogeneic STRO-3 + MPCs provided the rationale for our hypothesis that these cells were safe and might provide long-term clinical and joint structural benefits when administered to patients after ACL reconstruction.…”

Section: Introductionmentioning

confidence: 99%

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Safety, tolerability, clinical, and joint structural outcomes of a single intra-articular injection of allogeneic mesenchymal precursor cells in patients following anterior cruciate ligament reconstruction: a controlled double-blind randomised trial

Wang

Shimmin

Ghosh³

et al. 2017

Arthritis Res Ther

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BackgroundFew clinical trials have investigated the safety and efficacy of mesenchymal stem cells for the management of post-traumatic osteoarthritis. The objectives of this pilot study were to determine the safety and tolerability and to explore the efficacy of a single intra-articular injection of allogeneic human mesenchymal precursor cells (MPCs) to improve clinical symptoms and retard joint structural deterioration over 24 months in patients following anterior cruciate ligament (ACL) reconstruction.MethodsIn this phase Ib/IIa, double-blind, active comparator clinical study, 17 patients aged 18–40 years with unilateral ACL reconstruction were randomized (2:1) to receive either a single intra-articular injection of 75 million allogeneic MPCs suspended in hyaluronan (HA) (MPC + HA group) (n = 11) or HA alone (n = 6). Patients were monitored for adverse events. Immunogenicity was evaluated by anti-HLA panel reactive antibodies (PRA) against class I and II HLAs determined by flow cytometry. Pain, function, and quality of life were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and SF-36v2 scores. Joint space width was measured from radiographs, and tibial cartilage volume and bone area assessed from magnetic resonance imaging (MRI).ResultsModerate arthralgia and swelling within 24 h following injection that subsided were observed in 4 out of 11 in the MPC + HA group and 0 out of 6 HA controls. No cell-related serious adverse effects were observed. Increases in class I PRA >10% were observed at week 4 in the MPC + HA group that decreased to baseline levels by week 104. Compared with the HA group, MPC + HA-treated patients showed greater improvements in KOOS pain, symptom, activities of daily living, and SF-36 bodily pain scores (p < 0.05). The MPC + HA group had reduced medial and lateral tibiofemoral joint space narrowing (p < 0.05), less tibial bone expansion (0.5% vs 4.0% over 26 weeks, p = 0.02), and a trend towards reduced tibial cartilage volume loss (0.7% vs –4.0% over 26 weeks, p = 0.10) than the HA controls.ConclusionsIntra-articular administration of a single allogeneic MPC injection following ACL reconstruction was safe, well tolerated, and may improve symptoms and structural outcomes. These findings suggest that MPCs warrant further investigations as they may modulate some of the pathological processes responsible for the development of post-traumatic osteoarthritis following ACL reconstruction.Trial registrationClinicalTrials.gov (NCT01088191) registration date: March 11, 2010Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1391-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Safety, tolerability, clinical, and joint structural outcomes of a single intra-articular injection of allogeneic mesenchymal precursor cells in patients following anterior cruciate ligament reconstruction: a controlled double-blind randomised trial

Wang

Shimmin

Ghosh³

et al. 2017

Arthritis Res Ther

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“…The activities of the MPC were thought to stimulate chondrocyte biosynthesis of new matrix and attenuate local production and activity of catabolic mediators. 38 It should be noted that this research, although in animal models, leads to the possibility that the effect of MSC injections seen in the above-mentioned animal studies is just a transient one.…”

Section: Oa and Its Managementmentioning

confidence: 90%

Developments in stem cells: Implications for future joint replacements

Maclaine

McNamara

Bennett

et al. 2013

Proc Inst Mech Eng H

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Will stem cell research reverse the projected sevenfold increase in primary and revision knee replacements expected in the United States between 2005 and 2030? A focus on prevention and treatment of osteoarthritis may end the need for primary joint replacements. A more likely scenario can be described as slow and incremental changes in the prevention and treatment of osteoarthritis, accompanied by the continuing development of implant technology. Since the discovery of stem cells in the 1950s, research has increased exponentially. Expanded autologous chondrocytes, and more recently ex vivo expanded skeletal stem cells, are currently injected into osteochondral defects in the hope of regenerating cartilage and halting progression towards osteoarthritis. In addition, mesenchymal stem cells are being injected into human joints as a treatment for osteoarthritis despite a lack of quantitative research. Concurrently, stem cell research continues to contribute to chemical and topographical advancements in implant design. Advances in co-culture techniques mean it is possible that biologic articular replacements will develop prior to the cessation of the need for arthroplasty and radically change the nature of joint replacements. Whether it is through implant design or a potential cure for the pain attributable to osteoarthritis, as we hope to show in this 'forward look article', it is our opinion that stem cells will certainly impact future joint replacement.

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A12 Dose Dependent Chondroprotective Effects of Allogenic Stro-3+ Mesenchymal Precursor Stem Cells Following Direct Intra-Articular Injection Into Joints of an Ovine Model of Early Osteoarthritis

Cited by 2 publications

References 0 publications

Safety, tolerability, clinical, and joint structural outcomes of a single intra-articular injection of allogeneic mesenchymal precursor cells in patients following anterior cruciate ligament reconstruction: a controlled double-blind randomised trial

Safety, tolerability, clinical, and joint structural outcomes of a single intra-articular injection of allogeneic mesenchymal precursor cells in patients following anterior cruciate ligament reconstruction: a controlled double-blind randomised trial

Developments in stem cells: Implications for future joint replacements

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