Autologous conditioned serum applications in the treatment of musculoskeletal diseases: a narrative review

Aim: Autologous conditioned serum has been studied as a treatment option in musculoskeletal disorders and resulted in varying outcomes. This study aims to pool the current data on this matter. Materials & methods: Major databases were searched for the topics, and after screening the results, the final 21 papers (level of evidence I or II) were included. Results & conclusion: This study showed a major focus of the literature on the effectiveness of autologous conditioned serum in osteoarthritis, in which there is much high-quality evidence suggesting its safety and efficacy. Also, some of the available experiments are assessing its application in tendinopathies and radiculopathies which, despite positive results, recommend further evaluations on this topic.

Effects of Production Method and Repeated Freeze Thaw Cycles on Cytokine Concentrations and Microbial Contamination in Equine Autologous Conditioned Serum

Autologous conditioned serum (ACS) is a common intra-articular treatment for osteoarthritis in horses. The objective of this study was to investigate the influence of ACS preparation method on product contamination and concentrations of relevant cytokines and the influence of multiple freeze/thaw cycles. Blood was obtained from 10 healthy Thoroughbred horses and processed in parallel using a commercial and a non-commercial method to obtain ACS. Fluorescent microsphere immunoassay (FMIA) analysis was performed to quantify Interleukin 1 receptor antagonist (IL-1Ra), Interleukin-10 (IL-10), Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) concentrations in ACS obtained by both production methods. Effect of 3, 4 and 5 freeze/thaw cycles on concentrations of IL-1Ra, IL-10, IL-1β and TNF-α were assessed against baseline samples (2 cycles) in commercial ACS products. Standard aerobic and anaerobic culture methods were applied to both ACS products. Mixed effect one-way analyses of variance (ANOVA) were used to compare the two ACS production method for each cytokine. Repeated measures, mixed effect ANOVA were used to assess the effect of freeze/thaw on cytokine concentrations. Significance was set at P < 0.05. There was no difference in cytokine concentration between production methods (IL-1Ra P = 0.067, IL-1β P = 0.752, IL-10 P = 0.211 and TNF-α P = 0.25). Microbial growth was only observed in two samples obtained using the commercial production method. When compared to baseline, IL-1Ra concentration was decreased following the 5th freeze/thaw cycle (P < 0.001). These results suggest that the concentration of important cytokines are not influenced by ACS production method. When storing ACS samples for future use, freeze/thaw cycles associated with standard clinical practice are unlikely to influence cytokine concentrations. However, the lack of outcome measures associated with 1 or 2 freeze/thaw cycles represents a limitation of this study.

Effectiveness of intra-articular autologous-conditioned serum injection in knee osteoarthritis: a meta-analysis study

Aim: Knee osteoarthritis is a common disabling disorder, with no curative treatment. This study aims to assess autologous conditioned serum effectiveness in its treatment. Materials & methods: Following a systematic search (2000–2020) on major databases and screening and filtering processes, eight articles were included in the final analyses. The pooled effect of visual analog scale (VAS) and the Western Ontario and McMaster Universities (WOMAC) variables was evaluated before and after the intervention. Results: The combined standardized mean difference for the global WOMAC score was -2.44 and the combined weighted mean difference was -22.92. The combined standardized mean difference for the VAS score was -3.77 and the combined weighted mean difference was -32.37 (p < 0.000). Conclusion: This meta-analysis reported that the autologous conditioned serum can reduce pain and improve function (VAS and WOMAC outcome measures) in patients with knee osteoarthritis.

Intravenous Oxygen Insufflation (IOI) changes the IL-1-Ra:IL-1β ratio in Autologous Conditioned Serum

BackgroundInterleukin-1 (IL-1) is still regarded as the main offender that promotes the pro-inflammatory cascade in muscle injuries, tendopathies and especially in osteoarthritis. Thus, if present in high enough concentrations, IL-1receptor antagonist (IL-1Ra) has the potential to inhibit Interleukin-1. In this regard, autologous conditioned serum with an IL-1Ra/IL-1 ratio of at least >10 might fulfill optimal therapeutic effects. The purpose of this study was to analyze the combination of Regelsberger’s intravenous oxygen insufflation (IOI) with autologous conditioned serum (ACS) on IL-1Ra and IL-1 formation.MethodsVenous blood from 15 patients which underwent intravenous oxygen insufflation (IOI) for routinely preventive purposes was taken before the first, the 6th, and the 9th session of intravenous oxygen insufflation. IL-1β and IL-1-RA levels were quantified from serum and from autologous conditioned serum (ACS). ResultsPrevious intravenous oxygen insufflation treatments significantly reduced IL-1β levels in autologous conditioned serum from mean 67.85pg/ml (before the first treatment) down to mean 4.08pg/ml (before the 9th treatment). Post conditioning levels of IL-1Ra were not changed to any significant degree (before 1st/before6th/ before 9th treatment: 1038.37±140.51 / 900.30±79.24 / 902.84±95.68). Thus, the IL-1Ra:IL-1β ratio was altered on a molecule to molecule basis from a mean of 37.03:1 up to a mean 223.54:1 through the pretreatment. ConclusionIOI alters the IL-1Ra:IL-1ß ratio of autologous conditioned serum to a more favorable ratio which might mitigate the inflammatory cascade more efficaciously. Therefore, we suggest to perform intravenous oxygen insufflation on patients before they give blood for preparing ACS.

Intravenous oxygen insufflation (IOI) changes the IL-1-Ra:IL-1β ratio in autologous conditioned serum

Background Interleukin-1 (IL-1) is still regarded as the main offender that promotes the pro-inflammatory cascade in muscle injuries, tendopathies and especially in osteoarthritis. Thus, if present in high enough concentrations, IL-1receptor antagonist (IL-1Ra) has the potential to inhibit Interleukin-1. In this regard, autologous conditioned serum with an IL-1Ra/IL-1 ratio of at least > 10 might fulfill optimal therapeutic effects. The purpose of this study was to analyze the combination of Regelsberger’s intravenous oxygen insufflation (IOI) with autologous conditioned serum (ACS) on IL-1Ra and IL-1 formation. Methods Venous blood from 15 patients which underwent intravenous oxygen insufflation (IOI) for routinely preventive purposes was taken before the first, the 6th, and the 9th session of intravenous oxygen insufflation. IL-1β and IL-1-RA levels were quantified from serum and from autologous conditioned serum (ACS). Results Previous intravenous oxygen insufflation treatments significantly reduced IL-1β levels in autologous conditioned serum from mean 67.85pg/ml (before the first treatment) down to mean 4.08pg/ml (before the 9th treatment). Post conditioning levels of IL-1Ra were not changed to any significant degree (before 1st/before6th/ before 9th treatment: 1038.37 ± 140.51 / 900.30 ± 79.24 / 902.84 ± 95.68). Thus, the IL-1Ra:IL-1β ratio was altered on a molecule to molecule basis from a mean of 37.03:1 up to a mean 223.54:1 through the pretreatment. Conclusion IOI alters the IL-1Ra:IL-1ß ratio of autologous conditioned serum to a more favorable ratio which might mitigate the inflammatory cascade more efficaciously.

Bone Marrow Aspirate Concentrate Is More Effective Than Hyaluronic Acid and Autologous Conditioned Serum in the Treatment of Knee Osteoarthritis: A Retrospective Study of 505 Consecutive Patients

The aim of this study was to evaluate and compare the effectiveness of three different intra-articular injective treatments: hyaluronic acid (HA), autologous conditioned serum (ACS) and bone marrow aspirate concentrate (BMAC) for the treatment of knee osteoarthritis (OA). A Level III retrospective comparative clinical study was performed on 505 consecutive patients treated with HA (n = 171), ACS (n = 222) or BMAC (n = 112) for knee OA. The mean patient age was 52 ± 13 years; 54.5% were males. Collected data included patient demographics, symptoms, visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and radiographic classification of osteoarthritis grade using plain radiographs and advanced imaging. Clinical outcome was assessed at 3 and 12 months post treatment. Significant improvement in VAS and WOMAC was seen for all three treatments at the 3-month follow-up. At 12 months, VAS was improved in all three treatment groups, yet only BMAC sustained the improved WOMAC even in patients with more severe degenerative changes. This study shows that BMAC is more effective than HA and ACS in the treatment of symptomatic knee OA, especially in the patients with more severe degenerative changes.

Two different regenerative injections in patients diagnosed with secondary hip osteoarthritis: A report of two cases

Non-surgical treatment options are limited in hip osteoarthritis secondary to developmental dysplasia of the hip (DDH). Treatment of Autologous Conditioned Serum (ACS) is based on the high level of anti-inflammatory cytokine production of leukocytes in peripheral blood. It is an effective treatment option which contains the cytokines and the growth factors. Platelet Rich Plasma (PRP) is a form of treatment that stimulates natural healing steps through growth factors in platelets. In this case report we aimed to present the results of ACS and PRP injection in two patients who developed secondary coxarthrosis after DDH surgery. At the 1-year follow-up examination, patient’s functional scores improved and requirement for non-steroid anti-inflammatory drugs had significantly reduced. Regenerative injections either autologous conditioned serum or platelet rich plasma treatments are safe and effective treatments and can be recommended particularly for cases of secondary hip osteoarthritis associated with DDH.