Effects Of Autologous Conditioned Serum Research Articles

Effect of autologous conditioned serum (ACS) on histological characteristics and expression of soft tissue IL-1β gene after horizontal ridge augmentation surgery.

Horizontal ridge augmentation surgeries are common procedures in periodontics. Histological changes in soft tissues affect the success of surgery in many ways. Autologous conditioned serum (ACS) increases interleukin-1 receptor antagonist (IL-1Ra) and causes inflammation modulation. Therefore, the present study aimed to investigate the effect of ACS on histological changes and gene expression of soft tissues after horizontal ridge augmentation surgeries. This double-blind split-mouth clinical trial was performed on patients needing implants with horizontal ridge augmentation (n=21). The control and intervention groups were considered split-mouth in two areas of the patients' oral soft tissues. A collagen membrane impregnated with ACS was used on the test side, and only a collagen membrane was used on the control side. After four months, histological changes in soft tissues, such as the amount of connective tissue collagen, fibroblast and inflammatory cell counts, and expression of the IL-1β gene, were evaluated. The fibroblast counts in the ACS group were significantly higher than in the control group. In addition, ACS caused a significant increase in the amount of collagen in the soft tissues compared to the control group (P<0.01). However, the number of inflammatory cells was similar in the two groups (P>0.05). IL-1β gene expression was not significantly different between the case and control groups. Under the limitations of the present study and based on the results of histological examinations, ACS increased the number of fibroblasts and the amount of collagen in soft tissues without affecting inflammatory cells (P=0.562).

Evaluation of the effect of autologous conditioned serum on the radiographic characteristics of hard tissue after horizontal bone augmentation in implant dentistry.

Background. Bone deficiency in different areas is problematic in implant placement. Changes in histological, histomorphometric, and radiographic properties of hard tissues in the implant placement area affect many parameters of implant success. Autologous conditioned serum (ACS) is a blood product with high levels of IL1- receptor antagonists. Augmentation surgeries are required in many cases because implant placement in the edentulous areas requires a sufficient amount of bone. Therefore, this study radiographically evaluated the effect of autologous conditioned serum after horizontal bone augmentation. Methods. In this prospective RCT, 21 patients eligible patients were evaluated. The patient underwent horizontal ridge augmentation surgery in the area. The ACS-impregnated graft was in direct con-tact with the bone. The control side underwent the same surgical protocol without using ACS. Four months after surgery, a CBCT radiograph was taken, and radiographic changes in the two areas were calculated using the differences in the amount of bone formed in the horizontal dimension as well as the Hounsfield unit (HU). The data were reported using descriptive statistical methods, including means (standard deviations) and frequencies (percentages). According to the results of the Kolmog-orov-Smirnov test, the data had a normal distribution (P>0.05); therefore, paired t-test was used to compare the means of the parameters between the two groups. Results. IRadiographic examinations showed that the horizontal dimension of bone before surgery was similar between the two groups. However, after surgery in the ACS group (33.13±6.1), it was significantly higher than in the control group (62.1±86.4) (P>0.05). Also, the rate of horizontal dimension increase (the difference before and after surgery) in the ACS group was significantly higher than in the control group. Bone density before surgery was similar between the two groups. However, after surgery, there was a significant increase in the ACS group (75.56±330.42 HUs) compared to the control group (38.35±292.38 HUs) (P>0.05). Also, the rate of density increase (the difference before and after surgery) in the ACS group was significantly higher than in the control group. Conclusion. Radiographic evaluations of hard tissues showed a significant increase in the horizontal dimension of bone and density of newly formed bone using ACS compared to the control group.

In Vitro Anti-Inflammatory and Regenerative Effects of Autologous Conditioned Serum from Dogs with Osteoarthritis.

Simple SummaryAutologous conditioned serum (ACS) has benefits in managing osteoarthritis (OA) due to enriched mediators, including Interleukin-1 receptor antagonists (IL-1RA) and growth factors. Although ACS has become widely used in the clinic with favorable treatment outcomes in humans and animals, the study focusing on the therapeutic potential of ACS in dogs is limited. Therefore, this study investigated the therapeutic potential of ACS generated from dogs with OA, focusing on the potential anti-inflammatory and regenerative properties. We showed that ACS from OA dogs has essential mediators with immunomodulatory effects on reducing inflammation and promoting joint regeneration. We showed that ACS increased T cell suppression and FOXP3+ T cell expansion in vitro. In addition, ACS enhanced the proliferation of joint cells and promoted chondrocyte extracellular matrix gene expression. These actions are probably caused by the mediators in ACS, including transforming growth factor, vascular endothelial growth factor, and IL-1RA. This study provides insight into the benefits of an autologous bioactive substance derived from target users as a promising potential in regenerative strategies for OA management.Osteoarthritis (OA) is mostly incurable and non-regenerative with long-term complications. Autologous conditioned serum (ACS), which is enriched in Interleukin 1 receptor antagonists (IL-1RA) and growth factors, could be an alternative treatment to accelerate the positive therapeutic effects. ACS is proposed to alleviate inflammation by blocking IL-1 receptors. However, to date, there is no report focusing on the cell-mediated anti-inflammation and regenerative effect caused by ACS, especially the ACS from patients. Therefore, this study aims to investigate the therapeutic potential of ACS generated from dogs with spontaneous OA, focusing on its promising anti-inflammatory and regenerative properties in vitro compared to the matched plasma. We found that ACS prepared from ten OA dogs contained significant concentrations of IL-1RA, vascular endothelial growth factor, and transforming growth factor beta, which are key cytokines in anti-inflammation and angiogenesis. Furthermore, we found that ACS suppressed T cell activity by reducing proliferation of effector T cells and simultaneously expanding numbers of immune suppressive FOXP3+ T cells. Lastly, we showed that ACS enhanced the proliferation of osteocytes and fibroblasts and promoted extracellular matrix gene expression in primary chondrocyte culture. Therefore, these studies indicate that ACS prepared from dogs with OA is active as an immunomodulatory and regenerative strategy for use in OA management.

Effects of Autologous Conditioned Serum, Autologous Protein Solution, and Triamcinolone on Inflammatory and Catabolic Gene Expression in Equine Cartilage and Synovial Explants Treated With IL-1β in Co-culture.

Autologous conditioned serum (ACS) and autologous protein solution (APS) are newer therapeutic options for osteoarthritis (OA). Co-culture of cartilage and synovium stimulated with IL-1β produces a similar physiologic response to tissues from naturally-ocurring OA. The study objective was to investigate the effects of ACS, APS, and triamcinolone (TA) on inflammatory and catabolic gene expression of inflamed joint tissues in co-culture. Blood was collected and processed for ACS and APS from six horses. Cartilage and synovial explants were harvested from the stifle, placed in co-culture, and treated as: (1) unstimulated control (2) stimulated control (3) ACS at 25% v/v (4) ACS at 50% v/v (5) APS at 25% v/v (6) APS at 50% v/v, (7) TA (10−6 M). Treatment groups 2–7 were stimulated with IL-1β (10 ng/ml). Cultures were maintained for 96 hours, and then both media and explants were harvested for measurement of gene expression and protein. IL-1β stimulation significantly increased IL-1β (p = 0.029), IL-8 (p = 0.011) and MMP-3 (p = 0.043) expression in synovium and IL-1β (p = 0.003) and TNF-α (p = 0.001) expression in cartilage. Treatment with 50% ACS and APS v/v downregulated IL-1β expression in cartilage more than TA treatment (p = 0.001 and p = 0.0004) and APS downregulated MMP-1 expression in synovial membrane (p = 0.025). Treatment with ACS and APS caused a trend in upregulation of IL-10 expression in synovium and type II collagen and aggrecan expression in cartilage. PGE2 media concentrations were significantly reduced following treatment with APS (13.7-fold decrease, p = 0.0001) and ACS (4.13-fold decrease, p = 0.024); while TA did not reduce PGE2 significantly (2.3-fold decreased p = 0.406). As disease-modifying therapies, ACS and APS modified the cellular response from synovial membrane and articular cartilage. ACS and APS may offer an improved strategy to improve clinical signs of horses with naturally occurring OA, compared to TA treatment.

Is clinical effect of autologous conditioned serum in spontaneously occurring equine articular lameness related to ACS cytokine profile?

BackgroundBiologic’ therapies, such as autologous conditioned serum (ACS), are gaining popularity in treating orthopaedic conditions in equine veterinary medicine. Evidence is scarce regarding ACS constituents, and large inter-individual differences in cytokine and growth factor content have been demonstrated. The objective of the current study was to investigate the potential association between cytokine and growth factor content of ACS and clinical effect in harness racehorses with spontaneously occurring low-grade articular lameness. Horses received 3 intra-articular injections of ACS administered at approximately 2-week intervals. Lameness evaluation consisting of a trot-up with subsequent flexions tests was performed at inclusion and approximately 2 weeks after the last treatment (re-evaluation); horses were classified as responders when there was no detectable lameness on trot-up and a minimum of 50% reduction in flexion test scores at re-evaluation. Association between clinical outcome (responders vs. non-responders) and age, lameness grades at inclusion (both initial trot-up and after flexion tests), treatment interval, follow-up time and the ACS content of IL-1Ra, IGF-1 and TGF-β was determined by regression modelling.ResultsOutcome analysis was available for 19 of 20 included horses; 11 responded to treatment whereas 8 did not. There was considerable inter-individual variability in cytokine/growth factor content of ACS, and in the majority of the horses, the level of IL-10, IL-1β and TNF-α was below the detection limit. In the final multivariate logistic regression model, ACS content of IGF-1 and IL-1Ra was significantly associated with clinical response (P = 0.01 and P = 0.03, respectively). No association with clinical response was found for the other tested variables.ConclusionsThe therapeutic benefit of ACS may be related to higher levels of IL-1Ra and IGF-1. Our study corroborates previous findings of considerable inter-individual variability of cytokine- and growth factor content in ACS.

Investigation of the biomechanical and histopathological effects of autologous conditioned serum on healing of Achilles tendon

ObjectiveThe aim of this study to evaluate the effects of autologous conditioned serum (ACS) on the healing of transected rat Achilles tendons via the assessment of biomechanical and histological parameters. MethodsThe study was conducted on 45 male Sprague–Dawley rats. Five rats were used as donors for ACS preparation. Animals were randomly assigned to the experimental or control group. In both groups, the Achilles tendon was cut transversally and then sutured. In the placebo control and ACS-treated groups, saline or ACS, respectively, was injected into the repair zone three times after surgery. Ten rats from each group (ACS group, n = 20; control group, n = 20) were euthanized at days 15 and 30 after surgery for histopathological (n = 5) and biomechanical (n = 5) testing. The histopathological findings were interpreted using the Bonar and Movin scales. Tendon remodelling was evaluated via the immunohistochemical staining of collagen type 3. Biomechanical effects were assessed by tensile testing. ResultsThe Bonar and Movin scale scores were significantly better in the ACS-treated group on both day 15 (p = 0.003 and p = 0.003, respectively) and day 30 (p = 0.005 and p = 0.004, respectively). The immunohistochemical density of collagen type 3 was significantly lower in the ACS-treated group on day 30 (p = 0.018). The type 1/3 collagen ratios of the groups were similar on days 15 and 30, as determined by Sirius Red staining (p = 0.910 and p = 0.133, respectively). In the biomechanical assessment results, the ACS-treated group's maximum load to failure values were significantly higher on day 15 (p = 0.049). ConclusionInjection of ACS had a positive effect on the histopathological healing of rat Achilles tendons on days 15 and 30 and on biomechanical healing on day 15. ACS treatment contributed to lowering the collagen type 3 density by day 30. According to our study, ACS may be favourable for the treatment of human Achilles tendon injuries and tendinopathies.

A new treatment for hip osteoarthritis: clinical evidence for the efficacy of autologous conditioned serum

The purpose of the present study was to investigate the effect of intra-articular injections of autologous conditioned serum on human hip osteoarthritis and to test whether a potential treatment effect might be increased by additional injections of steroids and the recombinant interleukin-1 receptor antagonist protein anakinra. We compared the effects of autologous conditioned serum 46 hip osteoarthritis patients), autologous conditioned serum+cortisone (56 patients), and autologous conditioned serum+cortisone+recombinant interleukin-1 receptor antagonist protein (17 patients) in a retrospective clinical study by means of the Visual Analogue Scale for pain (pre- vs posttreatment). Over 14 months, treatment resulted in a large, statistically significant improvement for patients in all three groups, independent of the severity of osteoarthritis. Neither cortisone nor cortisone+recombinant interleukin-1 receptor antagonist protein increased the beneficial treatment effect over and above the effect of autologous conditioned serum alone. Autologous conditioned serum successfully reduces pain in hip osteoarthritis. In severe hip osteoarthritis, the sole application of autologous conditioned serum can be even more beneficial than the combination of autologous conditioned serum with steroids.

Effect of BMP-12, TGF-β1 and autologous conditioned serum on growth factor expression in Achilles tendon healing

Achilles tendon ruptures are devastating and recover slowly and incompletely. There is a great demand for biomolecular therapies to improve recovery, yet little is understood about growth factors in a healing tendon. Here, the role of growth factors during tendon healing in a rat model and their reaction to single and multiple growth factor treatment are explored. Rat tendons were transected surgically and resutured. The expression of bFGF, BMP-12, VEGF and TGF-β1 was assessed by immunohistochemical analysis one to 8 weeks after surgery. Paracrine effects of TGF-β1 or BMP-12 added by adenoviral transfer, as well as the effect of autologous conditioned serum (ACS) on growth factor expression, were evaluated. bFGF, BMP-12 and VEGF expression was highest 1 week after transection. bFGF and BMP-12 declined during the remaining period whereas VEGF expression persisted. TGF-β1 expression dramatically increased after 8 weeks. ACS treatment increased bFGF (P = 0.007) and BMP-12 (P = 0.004) expression significantly after 8 weeks. Also overall expression of bFGF, BMP-12 and TGF-β1 regardless of time point was significantly greater than controls with ACS treatment (P < 0.05). Both BMP-12 and TGF-β1 treatments had no significant effect. No effect was observed in VEGF with any treatment. bFGF, BMP-12, VEGF and TGF-β1 are differentially expressed during tendon healing. Additional BMP-12 or TGF-β1 has no significant influence, whereas ACS generally increases expression of all factors except VEGF. Staged application of multiple growth factors may be the most promising biomolecular treatment.