Cytokine profile of autologous conditioned serum for treatment of osteoarthritis, in vitro effects on cartilage metabolism and intra-articular levels after injection

Rutgers, Marijn; Saris, Daniël B.F.; Dhert, Wouter J.A.; Creemers, Laura B.

doi:10.1186/ar3050

Cited by 109 publications

(113 citation statements)

References 43 publications

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“…Researchers have looked at the cytokines present in ACS made from human and equine blood, but the list is unlikely to be extensive. 195,197,198 Also, the concentrations of cytokines have a high standard deviation, indicating there is a variance between individuals. 195,198 a.…”

Section: Autologous Conditioned Serummentioning

confidence: 99%

Cytokine and Growth Factor Concentrations in Canine Autologous Conditioned Serum

et al. 2016

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(ACADEMIC)The object of this study was to compare growth factor and cytokine profiles in canine autologous conditioned serum (ACS) to canine plasma. Blood collected from 16 medium to large breed dogs was used to produce ACS (Orthokine ® vet irap 10 syringes) and citrated plasma (control). Canine-specific ELISA assays were run per manufacturers' instructions for interleukin (IL)-10, IL-4, tumor necrosis factor (TNF)-α, insulin-like growth factor (IGF)-1, fibroblast growth factor (FGF)-2, transforming growth factor (TGF)-β1, IL-1β, and interleukin-1 receptor antagonist (IL-1ra). Serum, in addition to plasma and ACS, was collected from an additional 6 dogs for TNF-α, IL-1β, and IL-1ra analysis (total of 22 dogs). Data were analyzed for differences in cytokine concentrations between ACS, plasma, and serum using the Wilcoxon signed-rank test with significance set at P<.05.There was a large variability in growth factor and cytokine concentrations between individual dogs in both plasma and ACS. There were no significant differences in IL-10, TNF-α, IGF-1, FGF-2, and TGF-β1 concentrations between ACS, plasma, or serum. ACS concentrations of IL-1β (median, range; 46.3 pg/mL, 0-828.8) and IL-4 (0.0 pg/mL, 0-244.1) were significantly increased compared to plasma (36.6 pg/mL, 0-657.1 and 0.0 pg/mL, 0-0, respectively). IL-1ra concentrations in ACS (median, range; 3458.9 pg/mL, 1,243.1-12,089.0) were significantly higher than plasma (692.3 pg/mL, 422.5-1,475.6), as was the IL-1ra:IL-1β ratio (39.9 and 7.2, respectively).iii Cytokine and Growth Factor Profiles in Canine Autologous Conditioned SerumDominique Marie Sawyere ABSTRACT (PUBLIC)Osteoarthritis (OA) is a common cause of pain and suffering in dogs and is challenging to treat effectively Current treatment for OA merely mask the signs of pain and do not promote regeneration of the damaged cartilage or alter the course of the disease. Many treatments also cause harmful side effects. Autologous conditioned serum (ACS) is a biological therapy that controls inflammation within the joint by specifically blocking the inflammatory cytokine interleukin (IL)-1β. In humans and horses ACS relieves the pain from OA and promotes cartilage regeneration. The purpose of this study was to compare levels of pro-and anti-inflammatory cytokines in canine ACS to that of normal canine plasma with the hypothesis that levels of anti-inflammatory cytokines would be higher in ACS compared to controls and that levels of pro-inflammatory cytokines would remain unchanged. Paired blood samples were collected from 22 large breed healthy dogs and processed in either irap®10 syringes (ACS) or in anti-coagulant as a control. For the last 6 dogs an additional serum sample was collected. Growth factor and cytokine levels were determined using canine-specific ELISAs. One pro-inflammatory cytokine (IL-1β) and two anti-inflammatory cytokines (IL-1ra and IL-4) were significantly higher in the ACS compared to plasma and IL-1ra levels were also higher in serum compared with plasma samples. Other levels w...

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Section: Autologous Conditioned Serummentioning

confidence: 99%

Cytokine and Growth Factor Concentrations in Canine Autologous Conditioned Serum

et al. 2016

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“…These biochemical changes could explain observations made on monocytes, [4][5][6] since FTIR microspectroscopy (FTIR-MSP) has been widely used to study biochemical changes during cell growth and metabolism. [13][14][15] FTIR-MSP has an ability to provide simultaneous quantification of different metabolites and to identify them through unique spectral fingerprints, overcoming the requirement of separate analytical techniques for each biochemical component in low-abundant samples.…”

Section: Introductionmentioning

confidence: 81%

“…[1][2][3] Autologous-conditioned serum has been evaluated for treating osteoarthritis (OA) by studying the different levels of cytokines present and their net effect on the OA cartilage explants. 4 Treatment of monocytes with autologous serum indicated a change in surface expression of toll-like receptors and human leukocyte antigen, though they were not found to be related to blood serum factors. 5 Similarly, metabolites in plasma affect monocytes function.…”

Section: Introductionmentioning

confidence: 98%

Study of plasma-induced peripheral blood mononuclear cells survival using Fourier transform infrared microspectroscopy

et al. 2013

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Abstract. Components present in the acellular fraction of blood influence the blood cell survival and function and the response to biotic and abiotic factors. Human plasma and sera have been used as therapeutic agents and are known to increase cell survival. White blood cells in normal blood are exposed to plasma components in vivo, but the effect of such plasma components in vitro on adherent peripheral blood mononuclear cells (PBMCs) that includes monocytes has not been fully investigated. We cultured human PBMCs with autologous plasma and observed structural variation due to plasma addition in PBMCs along with increased cell survival. Light microscopy of the cells showed increased granularity in plasma-treated cells. Fourier transform infrared (FTIR) spectroscopy was used to elucidate the possible mechanism by studying the changes in the biochemical composition of the cells that explained the observations. FTIR spectroscopy of plasma-treated cells show altered spectral pattern in the mid-IR region, indicating increased phospholipid levels. Heat-stable components in the plasma possibly increase the differentiation of PBMCs, as evident by increased phospholipid metabolism. The data suggest that plasma-stimulated membrane biogenesis may contribute to PBMC survival by inducing them to differentiate into antigen presenting cells (APCs) like macrophages and dendritic cells.

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“…While this study is listed as double blind, the ACS group received six injections whereas the HA and saline group only received one, which may induce significant bias. More recent work by Rutgers et al highlighted that the increased IL-1ra content of ACS is accompanied by increased TNF-alpha amounts leading to a net zero effect on cartilage metabolism [53]. The largest detriment of these technologies is their short half-life in the synovial fluid.…”

Section: Growth Factor Treatmentsmentioning

confidence: 99%

The state of cartilage regeneration: current and future technologies

Yanke

Chubinskaya

2015

Curr Rev Musculoskelet Med

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It is clear that mature human articular cartilage does not have the innate ability to regenerate. Due to this, much effort has been put forth to work on bestowing this ability. While early data focused on more basic outcomes such as percentage of defect fill, the tissue formed was a "cartilage scar" or "hyaline-like" tissue. Even with more advanced technologies, it is clear that no current procedure is able to reconstitute the native structure and function of true hyaline cartilage. As research advancement has somewhat plateaued in this regard, it is crucial that future work focuses on a multifactorial approach, treating the joint as an organ system. The purpose of this review is to update readers on the most recent literature and controversies surrounding articular cartilage regeneration. Specific focus will be placed on current technologies available in the USA and the basic science to support them.

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Cytokine profile of autologous conditioned serum for treatment of osteoarthritis, in vitro effects on cartilage metabolism and intra-articular levels after injection

Cited by 109 publications

References 43 publications

Cytokine and Growth Factor Concentrations in Canine Autologous Conditioned Serum

Cytokine and Growth Factor Concentrations in Canine Autologous Conditioned Serum

Study of plasma-induced peripheral blood mononuclear cells survival using Fourier transform infrared microspectroscopy

The state of cartilage regeneration: current and future technologies

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