Equine allogeneic umbilical cord blood derived mesenchymal stromal cells reduce synovial fluid nucleated cell count and induce mild self‐limiting inflammation when evaluated in an lipopolysaccharide induced synovitis model

Williams, Lynn B.; Koenig, Judith B.; Black, Belinda; Gibson, Thomas W.G.; Sharif, Shayan; Koch, Thomas

doi:10.1111/evj.12477

Cited by 43 publications

(52 citation statements)

References 34 publications

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“…[119][120][121][122][123] Although it is a model of acute synovitis, it does induce significant increases in synovial fluid MMP activity and markers of type II collagen and proteoglycan degradation (C2C and 3-B-3) and synthesis (CPII and CS-846) that last for at least 1 week. 103,119,124 Moreover, if sustained by weekly stimulation for up to 12 weeks, the synovitis model induces hallmark features of OA in the synovium and cartilage in addition to clinical and radiographic changes, comparable to naturally occurring OA. [125][126][127] Given the strong agreement between our in vitro model and our in vivo study treating acute synovitis with BMNC, 37 this in vitro model should be considered for future studies assessing the mechanism of articular cell biology, pathobiology, and drug testing.…”

Section: Discussionmentioning

confidence: 99%

Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy

et al. 2020

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Synovial inflammation is a central feature of osteoarthritis (OA), elicited when local regulatory macrophages (M2‐like) become overwhelmed, activating an inflammatory response (M1‐like). Bone marrow mononuclear cells (BMNC) are a source of naïve macrophages capable of reducing joint inflammation and producing molecules essential for cartilage metabolism. This study investigated the response of BMNC to normal (SF) and inflamed synovial fluid (ISF). Equine BMNC cultured in autologous SF or ISF (n = 8 horses) developed into macrophage‐rich cultures with phenotypes similar to cells native to normal SF and became more confluent in ISF (~100%) than SF (~25%). BMNC cultured in SF or ISF were neither M1‐ nor M2‐like, but exhibited aspects of both phenotypes and a regulatory immune response, characterized by increasing counts of IL‐10+ macrophages, decreasing IL‐1β concentrations and progressively increasing IL‐10 and IGF‐1 concentrations. Changes were more marked in ISF and suggest that homeostatic mechanisms were preserved over time and were potentially favored by progressive cell proliferation. Collectively, our data suggest that intra‐articular BMNC could increase synovial macrophage counts, potentiating the macrophage‐ and IL‐10‐associated mechanisms of joint homeostasis lost during the progression of OA, preserving the production of cytokines involved in tissue repair (PGE2, IL‐10) generally impaired by frequently used corticosteroids.

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Section: Discussionmentioning

confidence: 99%

Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy

et al. 2020

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“…The TTJ, like the MCJ, has distinct advantages for joint studies, including its accessibility, and a large volume of synovial fluid for sampling. A previous study compared the TTJ to the MCJ to analyze joint responses to a therapeutic intervention (stem cells) following injection of an inflammatory agent ( 14 ). This study made the assumption that the TTJ and the MCJ would react similarly to lipopolysaccharide.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study ( 7 ) and the experiences of the authors of this current study with rIL-1β in the tibiotarsal joint (TTJ) led to the question whether the TTJ may have a different clinical and cytological response to the administration of rIL-1β than described for the MCJ. We felt this was an important question because previous studies have assumed the response to an inflammatory agent is equivalent between MCJ and TTJ and have drawn conclusions regarding the immunomodulatory ability of treatments such as mesenchymal stem cells using TTJ and MCJ as equivalent joints to investigate treatments ( 14 ). Further, variability in the TTJ and MCJ joint is important when determining the dose of rIL-1β appropriate for research studies, while comparing treatment responses and evaluating treatment strategies and clinical responses.…”

Section: Introductionmentioning

confidence: 99%

Induction of Synovitis Using Interleukin-1 Beta: Are There Differences in the Response of Middle Carpal Joint Compared to the Tibiotarsal Joint?

et al. 2018

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Background: The effects of recombinant interleukin-1β (rIL-1β) have been described for the middle carpal joint (MCJ). However, we are unaware of any studies that have described the cytological response of the tibiotarsal joint (TTJ) to rIL-1β or compared the clinical and cytological responses of the MCJ to the TTJ following the administration of intra-articular rIL-1β. Such information is critical for researchers planning to use rIL-1β to create acute synovitis models in horses.Objectives: To compare the clinical and cytological responses of the MCJ to the TTJ following administration of intra-articular rIL-1β.Methods: Twelve horses were used for the study. Eight horses received 75 ng of rIL-1β into the MCJ and four horses received 75 ng of rIL-1β into the TTJ. Clinical and cytological outcome parameters including lameness, joint circumference, joint effusion score, total nucleated cell count, cellular differentials, C-reactive protein, and prostaglandin-E2 concentrations were determined at baseline and multiple post-treatment time points over a 336 h period (2 weeks).Results: Recombinant IL-1β administered into the TTJ resulted in a significantly greater respiratory rate at 24 h and heart rate at 12 h when compared to rIL-1β administered into the MCJ. In addition, the TTJ had a significantly greater increase in joint circumference at 24 post-injection hour (PIH) and subjective effusion grade at 24 PIH and 336 PIH. The MCJ had significantly higher total protein concentration at 6 PIH, and a significantly higher NCC at 24 and 72 PIH when compared to the TTJ. Conversely, the TTJ had significantly higher neutrophilic infiltration than the MCJ at 6 PIH and 168 PIH.Conclusions: This study establishes that the same intra-articular dose of rIL-1 β elicits significantly different clinical and cytological responses in the MCJ compared to the TTJ in the equine model of intra-articular synovitis. In addition, clinical and cytological evidence of synovitis may persist up to or >1 week following intra-articular administration of rIL-1 β.

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“…It can be successfully treated with biologically based therapies such as platelet-rich plasma, or autologous conditioned serum (44, 45), or NSAIDs such as Ibuprofen or Naproxen (46). The MSCs-based therapies diminish the inflammatory response itself (12) and the intra-articular administration of MSCs has been found to reduce the nucleated cell counts in SF (47). Many authors have hypothesized that cell-free therapies may be safer and affordable than cell-based therapies (17, 18).…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes: Immunomodulatory Evaluation in an Antigen-Induced Synovitis Porcine Model

et al. 2017

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Synovitis is an inflammatory process associated with pain, disability, and discomfort, which is usually treated with anti-inflammatory drugs or biological agents. Mesenchymal stem cells (MSCs) have been also successfully used in the treatment of inflammatory-related diseases such as synovitis or arthritis. In the last years, the exosomes derived from MSCs have become a promising tool for the treatment of inflammatory-related diseases and their therapeutic effect is thought to be mediated (at least in part) by their immunomodulatory potential. In this work, we aimed to evaluate the anti-inflammatory effect of these exosomes in an antigen-induced synovitis animal model. To our knowledge, this is the first report where exosomes derived from MSCs have been evaluated in an animal model of synovitis. Our results demonstrated a decrease of synovial lymphocytes together with a downregulation of TNF-α transcripts in those exosome-treated joints. These results support the immunomodulatory effect of these exosomes and point out that they may represent a promising therapeutic option for the treatment of synovitis.

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Equine allogeneic umbilical cord blood derived mesenchymal stromal cells reduce synovial fluid nucleated cell count and induce mild self‐limiting inflammation when evaluated in an lipopolysaccharide induced synovitis model

Cited by 43 publications

References 34 publications

Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy

Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy

Induction of Synovitis Using Interleukin-1 Beta: Are There Differences in the Response of Middle Carpal Joint Compared to the Tibiotarsal Joint?

Mesenchymal Stem Cell-Derived Exosomes: Immunomodulatory Evaluation in an Antigen-Induced Synovitis Porcine Model

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