Osteoarthritis Therapy Research Articles

From dysfunction to healing: advances in mitochondrial therapy for Osteoarthritis

From dysfunction to healing: advances in mitochondrial therapy for Osteoarthritis

Extracorporeal Shock Wave Therapy (ESWT) vs. Exercise in Thumb Osteoarthritis (SWEX-TO): Prospective Clinical Trial at 6 Months

Rhizarthrosis is the most frequent form of osteoarthritis and is responsible for pain, disability and reduced functionality. The aim of the study is to investigate the clinical effects of shock wave treatment in patients suffering from arthritis of the first finger. A prospective clinical study was designed, in which 72 patients affected by rhizarthrosis were randomized to treatment with shock waves or exercises; in both groups an immobilization brace was used on the first finger. At recruitment and at 1, 3 and 6 months, patients received assessments of pain (VAS), functionality (FIHOA) and disability (DASH); furthermore, the perception of improvement was monitored during follow-ups (Roles and Maudsley Score). In both groups there was a significant improvement in all scores in the comparison between recruitment and 6 months. The perception of improvement was statistically better in the shock wave group than in the exercise group at 1, 3 and 6 months. The regression analysis showed that the reduction of VAS and DASH were statistically influenced by shock wave treatment (p < 0.001). Both therapies are effective in managing patients suffering from arthritis of the first finger, but the shock wave treatment could ensure greater persistence of improvements.

Intramuscular methylprednisolone in hand osteoarthritis: a retrospective cohort study

Abstract Objectives To explore patient characteristics associated with response to intramuscular methylprednisolone (MP) therapy in hand osteoarthritis (OA). Methods We performed an exploratory monocentric retrospective study. Patients with a clinical diagnosis of hand OA who visited our outpatient clinic between July 2016 and June 2021, and received at least once an intramuscular MP injection, were included. Clinical data, including laboratory and radiologic results, were retrieved from electronic patient records (EPRs). Patients’ reported response to MP and its duration in the first six months after injection was based on free text from the EPRs. Response was categorized into three groups: no response or worsening of symptoms, modest response, and good response. Duration of response was categorized as short-term (<2 weeks), or long-term (≥2 weeks). Multivariable logistic regression models were performed to determine factors associated with good response to therapy with methylprednisolone. Results Data from 262 hand OA patients (76% female) were analyzed. A good response was experienced by 150 patients (57.2%). Among those with modest to good response, the perceived response of 162 patients (80.6%) lasted 2 weeks or longer. Univariate regression analysis indicated that the level of CRP was associated with good response (odds ratio(OR) 1.08; 95% CI 1.00 to 1.17). However, multivariate regression analysis showed no statistical significant associations. Conclusion In this retrospective study, more than half of hand OA patients displayed good response to intramuscular MP administration. The possible relation between the presence of low-grade inflammation and the response to this therapy warrants further investigation.

Astaxanthin mediated repair of tBHP-Induced cellular injury in chondrocytes

ABSTRACT Objective This study investigates how astaxanthin (AST) counters tert-butyl hydroperoxide (tBHP)-induced cellular damage in C28/I2 chondrocytes, focusing on the circ-HP1BP3/miR-139-5p/SOD1 signaling pathway and its use in sustained-release microspheres for osteoarthritis treatment. Methods We employed a variety of techniques including real-time quantitative PCR, Western blot, ELISA, and dual-luciferase reporter gene assays to explore AST's molecular effects. Additionally, the efficacy of AST-loaded sustained-release microspheres was evaluated in vitro and in a mouse model of osteoarthritis. Results AST significantly enhanced SOD1 expression, reducing apoptosis and inflammation in damaged cells. The AST-loaded microspheres showed promising in vitro drug release, improved cell viability, and reduced oxidative stress. In the osteoarthritis mouse model, they effectively decreased joint inflammation and increased the expression of chondrocyte markers. Conclusion Astaxanthin effectively mitigates oxidative stress and inflammation in chondrocytes via the circ-HP1BP3/miR-139-5p/SOD1 pathway. The development of AST-loaded microspheres offers a novel and promising approach for osteoarthritis therapy, potentially extending to osteoarthritis treatment.

Controlled Stimulus-Responsive Delivery Systems for Osteoarthritis Treatment

Osteoarthritis (OA), a common and disabling degenerative joint disease, affects millions of people worldwide and imposes a considerable burden on patients and society due to its high prevalence and economic costs. The pathogenesis of OA is closely related to the progressive degradation of articular cartilage and the accompany inflammation; however, articular cartilage itself cannot heal and modulate the inflammation due to the lack of nerves, blood vessels, and lymph-vessels. Therefore, reliable and effective methods to treat OA remain highly desired. Local administration of drugs or bioactive materials by intra-articular injection of the delivery system represents a promising approach to treat OA, especially considering the prolonged joint retention, cartilage or chondrocytes targeting, and stimuli-responsive release to achieve precision OA therapy. This article summarizes and discusses the advances in the currently used delivery systems (nanoparticle, hydrogel, liposome, and microsphere) and then focuses on their applications in OA treatment from the perspective of endogenous stimulus (redox reactions, pH, enzymes, and temperature) and exogenous stimulus (near-infrared, magnetic, and ultrasound)-responsive release. Finally, the challenges and potential future directions for the development of nano-delivery systems are summarized.

A Core-Brush Nanoplatform with Enhanced Lubrication and Anti-Inflammatory Properties for Osteoarthritis Treatment.

Osteoarthritis (OA) is recognized as a highly friction-related joint disease primarily associated with increased joint friction and inflammation due to pro-inflammatory M1-type macrophage infiltration in the articular cavity. Therefore, strategies to simultaneously increase lubrication and relieve inflammation to remodel the damaged articular microenvironment are of great significance for enhancing its treatment. Herein, a multifunctional core-brush nanoplatform composed of a ROS-scavenging polydopamine-coated SiO2 core and lubrication-enhancing zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) brush and loaded with the anti-inflammatory drug curcumin by a reactive oxygen species (ROS)-liable conjugation (named as SiO2@PP-Cur) is rationally designed. Benefiting from the grafted zwitterionic PMPC brush, a tenacious hydration layer with enhanced lubricity for reducing joint abrasions is developed. More importantly, based on the mono-iodoacetic acid-induced arthritis (MIA) rat model, intra-articular injection of SiO2@PP-Cur nanoplatform can effectively alleviate articular inflammation via promoting macrophage polarization from the pro-inflammatory M1 to anti-inflammatory M2 state by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and attenuating the degradation of cartilage matrix, resulting in the remodeling of the damaged microenvironment into a pro-regenerative microenvironment. As a result, SiO2@PP-Cur can considerably inhibit OA progression. Therefore, the work may provide a novel strategy for the development of an advanced core-brush nanoplatform for enhanced OA therapy.

The Role of Cartilage Tissue Engineering in Osteoarthritis Treatment: The Bench to Bedside Translation

ABSTRACTCartilage tissue engineering holds huge promise for joint defects and osteoarthritis (OA) conditions which otherwise have limited treatment options due to cartilage's inherent inability to self‐repair. Chemical cues play a pivotal role in regulating chondrocyte behavior and matrix synthesis. Strategies utilizing growth factors, small molecules, and biomaterial‐based delivery systems aim to modulate chondrogenic differentiation, proliferation, and matrix deposition, while recent insights emphasize the significance of mimicking native tissue gradients for optimal regeneration outcomes. Mechanical stimuli profoundly influence chondrocyte phenotype and function, necessitating precise control of the mechanical microenvironment in tissue engineering strategies. Advances in biomaterial design, scaffold fabrication, and bioreactor systems facilitate the tailored modulation of mechanical cues, including substrate stiffness, topography, and dynamic loading regimes. This review showcases the latest advancements in engineering both the chemical and mechanical microenvironment to enhance chondrocyte regeneration. Furthermore, exploring the synergistic effects of combining chemical and mechanical cues underscores the importance of multifaceted approaches in promoting robust chondrocyte regeneration. The review also addresses challenges and future directions in the field, such as achieving spatially organized tissue architecture and integrating patient‐specific factors, to propel advancements in cartilage tissue engineering. We also conducted a comprehensive enlistment for the clinical trials and tissue engineering‐based marketed products for OA therapy.

Edge advances in nanodrug therapies for osteoarthritis treatment

As global population and lifestyles change, osteoarthritis (OA) is becoming a major healthcare challenge world. OA, a chronic condition characterized by inflammatory and degeneration, often present with joint pain and can lead to irreversible disability. While there is currently no cure for OA, it is commonly managed using nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and glucosamine. Although these treatments can alleviate symptoms, it is difficult to effectively deliver and sustain therapeutic agents within joints. The emergence of nanotechnology, particularly in form of smart nanomedicine, has introduced innovative therapeutic approaches for OA treatment. Nanotherapeutic strategies offer promising advantages, including more precise targeting of affected areas, prolonged therapeutic effects, enhanced bioavailability, and reduced systemic toxicity compared to traditional treatments. While nanoparticles show potential as a viable delivery system for OA therapies based on encouraging lab-based and clinical trials results, there remails a considerable gap between current research and clinical application. This review highlights recent advances in nanotherapy for OA and explore future pathways to refine and optimize OA treatments strategies.

Targeted non-invasive Metformin-Curcumin co-loaded nanohyaluosomes halt osteoarthritis progression and improve articular cartilage structure: A preclinical study

Osteoarthritis (OA) is a degenerative disease that affects the quality of life in elderly and young populations. Current therapies using corticosteroids and non-steroidal anti-inflammatory drugs via parenteral or oral routes show limited ability to retard progression of the disease and achieve long term effectiveness and safety. Herein, the potential of MT-Cur combinatorial nano-formulations in OA management was explored for the first time. MT-Cur loaded nanohyaluosomes (MT-Cur-HL1) were designed for topical administration of the combined therapy in OA. The optimized MT-Cur-HL1 showed particle size 247.7 ± 3.7 nm, zeta potential −37.3 ± 0.4 mV; and entrapment efficiency (%EE) 70.22 %±0.303 and 76.7 %±0.077 for MT and Cur, respectively. MT-Cur-HL1 exhibited sustained drug release over 24 h and were stable over 3 months at 4 °C in terms of P.S., ZP and %EE. A detailed preclinical study, using MIA-induced osteoarthritis rat model, revealed the most significant anti-arthritic effect and halted OA progression of MT-Cur-HL1. This was proved to be mainly through the potentiation of p-AMPK signaling that ultimately led to suppression of its downstream TLR4/ NF-κB signaling pathway with subsequent reduction in MMP13 and ADAMTS5 induced chondrocytes degeneration. This study proved that this trajectory effectively promotes a significant improvement in the articular cartilage structure and reinforcement of joint mobility with an efficient antinociceptive effect. In conclusion, the novel MT-Cur coloaded nanohyaluosomes offer a promising non-invasive approach for the local management of OA.

Lymphocyte-Derived Engineered Apoptotic Bodies with Inflammation Regulation and Cartilage Affinity for Osteoarthritis Therapy.

Apoptotic bodies as plentiful extracellular vesicles generated from apoptotic cells play a central role in signal transduction and homeostasis regulation and simultaneously switch death to regeneration to a certain extent. Herein, we designed engineered apoptotic bodies derived from T cells to have the capacity of inflammation regulation and cartilage affinity. The engineered apoptotic bodies as a natural anti-inflammation factor were encapsulated into lubricating hydrogel microspheres to achieve an injectable microsphere complex for the treatment of osteoarthritis (OA). In the above therapeutic system, the engineered apoptotic bodies acted as a biochemical cue to regulate the inflammatory microenvironment and promote chondrocyte cartilage homeostasis, whereas the lubricating hydrogel microspheres served as a biophysical stimulation to effectively reduce the friction of the cartilage surface, restore the cartilage stress, and control the slow delivery of the encapsulated engineered apoptotic bodies by friction degradation. Consequently, the current work creates an injectable and multifunctional therapeutic microsphere to advance cartilage remodeling and OA therapy.

A natural polyphenolic nanoparticle--knotted hydrogel scavenger for osteoarthritis therapy

Exploring highly efficient and cost-effective biomaterials for osteoarthritis (OA) treatment remains challenging, as current therapeutic strategies are difficult to eradicate the excessive reactive oxygen species (ROS) and nitric oxide (NO) at damaged sites. Tea polyphenol (TP) nanoparticles (NPs), a nature-inspired antioxidant in combination with 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a NO scavenger, could provide maximized positive therapeutic effects on OA by eradicating both ROS and NO. Notably, this combination not only improves the half-life of the TP monomer and the drug loading efficiency of carboxy-PTIO but also prevents nitrite from being harmful to tissue. Moreover, the protonation ability of carboxy-PTIO allows smart acid-responsive release in response to environmental pH, which provides conditioned treatment strategies for OA. In in vitro experiments, TP/PTIO NPs downregulated proinflammatory cytokine release via synergistic removal of ROS and NO and suppression of ROS/NF-κB and iNOS/NO/Caspase-3 signaling. For in vivo experiments, NPs were cross-linked with 4-arm-PEG-SH to form an injectable hydrogel system. The release of TP and carboxy-PTIO from the system efficiently prevents cartilage inflammation and damage via similar signaling pathways. Overall, the proposed system provides an efficient approach for OA therapy.

Stem cell therapy for osteoarthritis: Functional cartilage regeneration using 3d bioprinting technology

Stem cell therapy for osteoarthritis: Functional cartilage regeneration using 3d bioprinting technology Osteoarthritis presents a significant societal and economic burden. Stina Simonsson from the University of Gothenburg explains how EU-funded projects are using 3D bioprinting to create functional cartilage for OA treatment. Osteoarthritis (OA) is a widespread condition that affects millions of people globally. As the population ages and the obesity epidemic continues, the incidence of OA is expected to increase. 3D bioprinting and stem cell therapies are heralded as the future of medical treatments for such conditions. OA affects a significant portion of the Swedish population. Estimates suggest that about 7-8% of the population is diagnosed with OA, which translates to roughly 700,000 to 800,000 individuals. The condition is more common among older adults, with a higher prevalence observed in those over the age of 65.

Biological Treatment of Knee Osteoarthritis. The Role of Mesenchymal Stem Cells and Platelet‐Rich Plasma

Summary. Osteoarthritis (OA) is the most common joint disease, which is associated with growing population ageing. Beyond conventional medical and surgical interventions, there is an increasing number of “biological” therapies. These therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. The aim of this review was to analyze current evidence regarding mesenchymal stem cells (MSCs) therapy and platelet-rich plasma (PRP). There is some evidence to suggest symptomatic improvement with MSCs injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI, and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. Although controlled studies have been conducted to evaluate effectiveness in OA, they have been often of small size, limited statistical power, uncertain blindness, and using various methodologies. These deficiencies leave open the question of whether they have been validated as effective therapies in OA. The conclusions of this review are that all biological interventions definitely require clinical trials with robust methodology to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects.

Targeted Therapy of Osteoarthritis via Intra-Articular Delivery of Lipid-Nanoparticle-Encapsulated Recombinant Human FGF18 mRNA.

Fibroblast growth factor 18 (FGF18) emerges as a promising therapeutic target for osteoarthritis (OA). In this study, a novel articular cavity-localized lipid nanoparticle (LNP) named WG-PL14 is developed. This optimized formulation has a nearly 30-fold increase in mRNA expression as well as better articular cavity enrichment compared to commercial lipids MC3 when performing intra-articular injection. Then, a mRNA sequence encoding recombinant human FGF18 (rhFGF18) for potential mRNA therapy in OA is optimized. In vitro assays confirm the translation of rhFGF18 mRNA into functional proteins within rat and human chondrocytes, promoting cell proliferation and extracellular matrix (ECM) synthesis. Subsequently, the therapeutic efficacy of the LNP-rhFGF18 mRNA complex is systematically assessed in a mouse OA model. The administration exhibits several positive outcomes, including an improved pain response, upregulation of ECM-related genes (e.g., AGRN and HAS2), and remodeling of subchondral bone homeostasis compared to a control group. Taken together, these findings underscore the potential of localized LNP-rhFGF18 mRNA therapy in promoting the regeneration of cartilage tissue and mitigating the progression of OA.

Lifetime Cost-Effectiveness of Structured Education and Exercise Therapy for Knee Osteoarthritis in Australia.

Structured education and exercise therapy programs have been proposed to reduce reliance on total knee replacement (TKR) surgery and improve health care sustainability. The long-term cost-effectiveness of these programs is unclear. To estimate the lifetime cost-effectiveness of implementing a national structured education and exercise therapy program for individuals with knee osteoarthritis with the option for future TKR compared with usual care (TKR for all). This economic evaluation used a life table model in combination with a Markov model to compare costs and health outcomes of a national education and exercise therapy program vs usual care in the Australian health care system. Subgroup, deterministic, and probabilistic sensitivity analyses were completed. A hypothetical cohort of adults aged 45 to 84 years who would undergo TKR was created. Structured education and exercise therapy intervention provided by physiotherapists. The comparator was usual care where all people undergo TKR without accessing the program in the first year. Incremental net monetary benefit (INMB), with an incremental cost-effectiveness ratio threshold of 28 033 Australian dollars (A$) per quality-adjusted life-year (QALY) gained, was calculated from a health care perspective. Transition probabilities, costs, and utilities were estimated from national registries and a randomized clinical trial. The hypothetical cohort included 61 394 individuals (53.9% female; 93.6% aged ≥55 years). Implementation of an education and exercise therapy program resulted in a lifetime cost savings of A$498 307 942 (US $339 922 227), or A$7970 (US $5537) per individual, and resulted in fewer QALYs (0.43 per individual) compared with usual care. At a population level, education and exercise therapy was not cost-effective at the lifetime horizon (INMB, -A$4090 [-US $2841]). Subgroup analysis revealed that the intervention was cost-effective only for the first 9 years and over a lifetime only in individuals with no or mild pain at baseline (INMB, A$11 [US $8]). Results were robust to uncertainty around model inputs. In this economic evaluation of structured education and exercise therapy compared with usual care, the intervention was not cost-effective over the lifetime for all patients but was for the first 9 years and for those with minimal pain. These findings point to opportunities to invest early cost savings in additional care or prevention, including targeted implementation to specific subgroups.

Genicular Nerve Block for Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

Genicular nerve block (GNB) has emerged as a novel nonsurgical therapy for symptomatic knee osteoarthritis (KOA). The objective was to evaluate GNB versus placebo and other intra-articular (IA) therapies. The Medline, Embase, and Scopus databases were searched from their inception to January 2021. Only randomized controlled trials (RCTs) were included. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was tested with the I2 index. Regarding pain statistically significant scores were demonstrated at 1 and 3 months overall total effect of 1.43 (95% CI, 0.86, 1.99; P= 0.00001; I2 =85%). Similarly, for knee function a total effect of 0.71 (95% CI, 0.35, 1.06; P= 0.00001; I2 =69%) at 1 and 3 months, statistically significant. The minimal clinically important difference regarding pain was achieved at 1 and 3 months. Although, GNB achieved the MCID for KOA pain and statistically significant results for knee functions. We cannot recommend its routine use besides being a safe procedure so far, evidence is fair on GNB for primary KOA due to study heterogeneity and limited follow-up.

Melatonin enhances therapeutic outcomes of adipose tissue-derived mesenchymal stem cell therapy in rat osteoarthritis by reducing TNF-α and IL-1β-induced injuries.

Although adipose tissue-derived mesenchymal stem cell (ADSC) transplantation has been effectively used to treat osteoarthritis (OA), the low cell survival rate induced by the inflammatory and oxidative stress, severely affects the therapeutic efficiency of ADSC transplantation in OA. This study was designed to evaluate whether melatonin pretreatment could improve ADSC survival and its therapeutic efficacy in OA. The papain-induced OA rats were pretreated with melatonin via intra-articular injection and then intra-articular injected with indocyanine green (ICG)-labeled ADSCs (3 × 106/rat). Afterward, ADSC retention was evaluated by NIR-II fluorescence imaging. The tibia and synovial fluid were collected for histopathological examination and ELISA assay, respectively. To confirm the anti-inflammatory effect of melatonin, a TNF-α and IL-1β-induced cell model was used to evaluate the protective effects of melatonin on ADSC viability, cell apoptosis, and migration. Our results showed that melatonin pretreatment enhanced ADSC survival and improved the therapeutic effects of ADSC transplantation on cartilage repair, and anti-inflammation by reducing TNF-α, IL-6, IL-1β, and IL-12 in vivo. In particular, we also found that melatonin promoted ADSC viability and migration, and reduced cell apoptosis in vitro. In conclusion, this study supports that melatonin pretreatment can effectively improve ADSC survival and therapeutic efficiency in OA by reducing inflammatory injuries, which provides a novel strategy for enhancing ADSC therapy.

ESC-sEVs alleviate non-early-stage osteoarthritis progression by rejuvenating senescent chondrocytes via FOXO1A-autophagy axis but not inducing apoptosis

Osteoarthritis (OA) is a common joint degenerative disease which currently lacks satisfactory disease-modifying treatments. Oxidative stress-mediated senescent chondrocytes accumulation is closely associated with OA progression, which abrogates cartilage metabolism homeostasis by secreting senescence-associated secretory phenotype (SASP) factors. Numerous studies suggested mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) have been regarded as promising candidates for OA therapy. However, MSC-sEVs were applied before the occurrence of cartilage degeneration or at early-stage OA, while in clinical practice, most OA patients who present with pain are already in non-early-stage. Recently, embryonic stem cells-derived sEVs (ESC-sEVs) have been reported to possess powerful anti-aging effects. However, whether ESC-sEVs could attenuate non-early-stage OA progression remains unknown. In this study, we demonstrated ESC-sEVs ameliorated senescent phenotype and cartilage destruction in both mechanical stress-induced non-early-stage posttraumatic OA and naturally aged mice. More importantly, we found ESC-sEVs alleviated senescent phenotype by rejuvenating aged chondrocytes but not inducing apoptosis. We also provided evidence that the FOXO1A-autophagy axis played an important role in the anti-aging effects of ESC-sEVs. To promote clinical translation, we confirmed ESC-sEVs reversed senescent phenotype in ex-vivo cultured human end-stage OA cartilage explants. Collectively, our findings reveal that ESC-sEVs-based therapy is of high translational value in non-early-stage OA treatment.

Human uncultured adipose-derived stromal vascular fraction shows therapeutic potential against osteoarthritis in immunodeficient rats via direct effects of transplanted M2 macrophages

BackgroundThe uncultured adipose-derived stromal vascular fraction (SVF), consisting of adipose-derived stromal cells (ADSCs), M2 macrophages (M2Φ) and others, has shown therapeutic potential against osteoarthritis (OA), however, the mechanisms underlying its therapeutic effects remain unclear. Therefore, this study investigated the effects of the SVF on OA in a human-immunodeficient rat xenotransplantation model.MethodsOA model was induced in the knees of female immunodeficient rats by destabilization of the medial meniscus. Immediately after the surgery, human SVF (1 × 105), ADSCs (1 × 104), or phosphate buffered saline as a control group were transplanted into the knees. At 4 and 8 weeks postoperatively, OA progression and synovitis were analyzed by macroscopic and histological analyses, and the expression of collagen II, SOX9, MMP-13, ADAMTS-5, F4/80, CD86 (M1), CD163 (M2), and human nuclear antigen (hNA) were evaluated immunohistochemically. In vitro, flow cytometry was performed to collect CD163-positive cells as M2Φ from the SVF. Chondrocyte pellets (1 × 105) were co-cultured with SVF (1 × 105), M2Φ (1 × 104), and ADSCs (1 × 104) or alone as a control group, and the pellet size was compared. TGF-β, IL-10 and MMP-13 concentrations in the medium were evaluated using enzyme-linked immunosorbent assay.ResultsIn comparison with the control and ADSC groups, the SVF group showed significantly slower OA progression and less synovitis with higher expression of collagen II and SOX9, lower expression of MMP-13 and ADAMTS-5, and lower F4/80 and M1/M2 ratio in the synovium. Only the SVF group showed partial expression of hNA-, CD163-, and F4/80-positive cells in the rat synovium. In vitro, the SVF, M2Φ, ADSC and control groups, in that order, showed larger pellet sizes, higher TGF-β and IL-10, and lower MMP-13 concentrations.ConclusionsThe M2Φ in the transplanted SVF directly affected recipient tissue, enhancing the secretion of growth factors and chondrocyte-protecting cytokines, and partially improving chondrocytes and joint homeostasis. These findings indicate that the SVF is as an effective option for regenerative therapy for OA, with mechanisms different from those of ADSCs.

Blood Products and Stem Cells in Osteoarthritis Therapy

The principle of regenerative medicine in the treatment of osteoarthritis pursues a functional restoration of cartilage tissue instead of just repairing cartilage defects. The use of blood products is intended to inhibit chronic inflammatory processes and promote tissue regeneration. Intraarticular injection of autologous platelet-rich plasma (PRP) is a prominent procedure. Clinical evidence supports PRP injection over hyaluronic acid or glucocorticoid injection. Comparability of studies is difficult due to missing standardisation of production procedures, dosing and donor variability. In particular, whether presence of residual leukocytes is required or should be avoided is an open debate. In contrast, stem cell therapies in osteoarthritis therapy are often based on mesenchymal stem cells (MSC) from adipose tissue or bone marrow aspirate. Different sources of MSC might render the cells more suitable for application in a given context. Nevertheless, it became evident that their secretome rather than the cells themselves are responsible for observed regenerative processes. Research on the mechanisms of action have focused on growth factors. However, an overlooked component of blood products called extracellular vesicles (EV) came to the center of attention, which are also released by MSC as intercellular signal carriers. EV cargo molecules such as miRNAs open up new dimensions in the investigation and explanation of clinically observed anti-inflammatory and regenerative effects.