scholarly journals A Pilot Clinical Study of Hyperacute Serum Treatment in Osteoarthritic Knee Joint: Cytokine Changes and Clinical Effects

2021 ◽  
Vol 43 (2) ◽  
pp. 637-649
Author(s):  
Isabel Olmos Calvo ◽  
Eszter Fodor ◽  
Dorottya Kardos ◽  
István Hornyák ◽  
Adél Hinsenkamp ◽  
...  

The serum fraction of platelet-rich fibrin (hyperacute serum) has been shown to improve cartilage cell proliferation in in vitro osteoarthritic knee joint models. We hypothesize that hyperacute serum may be a potential regenerative therapeutic for osteoarthritic knees. In this study, the cytokine milieu at the synovial fluid of osteoarthritic knee joints exposed to hyperacute serum intraarticular injections was investigated. Patients with knee osteoarthritis received three injections of autologous hyperacute serum; synovial fluid was harvested before each injection and clinical monitoring was followed-up for 6 months. Forty osteoarthritic-related cytokines, growth factors and structural proteins from synovial fluid were quantified and analysed by Multivariate Factor Analysis. Hyperacute serum provided symptomatic relief regarding pain and joint stability for OA patients. Both patients “with” and “without effusion knees” had improved VAS, KOOS and Lysholm-Tegner scores 6 months after of hyperacute serum treatment. Synovial fluid analysis revealed two main clusters of proteins reacting together as a group, showing strong and significant correlations with their fluctuation patterns after hyperacute serum treatment. In conclusion, hyperacute serum has a positive effect in alleviating symptoms of osteoarthritic knees. Moreover, identified protein clusters may allow the prediction of protein expression, reducing the number of investigated proteins in future studies.

2021 ◽  
Vol 22 (4) ◽  
pp. 1996 ◽  
Author(s):  
Christine M. Khella ◽  
Rojiar Asgarian ◽  
Judith M. Horvath ◽  
Bernd Rolauffs ◽  
Melanie L. Hart

Understanding the causality of the post-traumatic osteoarthritis (PTOA) disease process of the knee joint is important for diagnosing early disease and developing new and effective preventions or treatments. The aim of this review was to provide detailed clinical data on inflammatory and other biomarkers obtained from patients after acute knee trauma in order to (i) present a timeline of events that occur in the acute, subacute, and chronic post-traumatic phases and in PTOA, and (ii) to identify key factors present in the synovial fluid, serum/plasma and urine, leading to PTOA of the knee in 23–50% of individuals who had acute knee trauma. In this context, we additionally discuss methods of simulating knee trauma and inflammation in in vivo, ex vivo articular cartilage explant and in vitro chondrocyte models, and answer whether these models are representative of the clinical inflammatory stages following knee trauma. Moreover, we compare the pro-inflammatory cytokine concentrations used in such models and demonstrate that, compared to concentrations in the synovial fluid after knee trauma, they are exceedingly high. We then used the Bradford Hill Framework to present evidence that TNF-α and IL-6 cytokines are causal factors, while IL-1β and IL-17 are credible factors in inducing knee PTOA disease progresssion. Lastly, we discuss beneficial infrastructure for future studies to dissect the role of local vs. systemic inflammation in PTOA progression with an emphasis on early disease.


Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1116 ◽  
Author(s):  
Mazzotti ◽  
Teti ◽  
Falconi ◽  
Chiarini ◽  
Barboni ◽  
...  

Osteoarthritis is a degenerative disease that strongly correlates with age and promotes the breakdown of joint cartilage and subchondral bone. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stromal cells (MSCs) isolated from adult tissues. It seems that MSCs derived from synovial joint tissues exhibit superior chondrogenic ability, but their unclear distribution and low frequency actually limit their clinical application. To date, the influence of aging on synovial joint derived MSCs’ biological characteristics and differentiation abilities remains unknown, and a full understanding of the mechanisms involved in cellular aging is lacking. The aim of this study was therefore to investigate the presence of age-related alterations in synovial fluid MSCs and their influence on the potential ability of MSCs to differentiate toward chondrogenic phenotypes. Synovial fluid MSCs, isolated from healthy equine donors from 3 to 40 years old, were cultured in vitro and stimulated towards chondrogenic differentiation for up to 21 days. An equine model was chosen due to the high degree of similarity of the anatomy of the knee joint to the human knee joint and as spontaneous disorders develop that are clinically relevant to similar human disorders. The results showed a reduction in cell proliferation correlated with age and the presence of age-related tetraploid cells. Ultrastructural analysis demonstrated the presence of morphological features correlated with aging such as endoplasmic reticulum stress, autophagy, and mitophagy. Alcian blue assay and real-time PCR data showed a reduction of efficiency in the chondrogenic differentiation of aged synovial fluid MSCs compared to young MSCs. All these data highlighted the influence of aging on MSCs’ characteristics and ability to differentiate towards chondrogenic differentiation and emphasize the importance of considering age-related alterations of MSCs in clinical applications.


2004 ◽  
Vol 38 (6) ◽  
pp. 561-571 ◽  
Author(s):  
Christopher J.L. Silwood ◽  
Ian C. Chikanza ◽  
K. Elizabeth Tanner ◽  
Julia C. Shelton ◽  
John G. Bowsher ◽  
...  

2021 ◽  
pp. 036354652110551
Author(s):  
Ala Altaie ◽  
Thomas G. Baboolal ◽  
Owen Wall ◽  
Hemant Pandit ◽  
Elena Jones ◽  
...  

Background: Synovial fluid (SF) mesenchymal stem cells (MSCs) are derived from the synovial membrane and have cartilage repair potential. Their current use in clinical practice is largely exploratory. As their numbers tend to be small, therapeutic procedures using MSCs typically require culture expansion. Previous reports indicate that the stem cell–mobilizing device (STEM device) intraoperatively increases SF-MSCs. Purpose: This study evaluated the chondrogenic potential of non–culture expanded synovium-mobilized MSCs and SF-microfragments obtained after enrichment using the STEM device and ascertained if device-mediated synovial membrane manipulation facilitated ongoing MSC release. Study Design: Controlled laboratory study. Methods: Two samples of aspiration fluid were collected intraoperatively before and after STEM device utilization from patients (n = 16) undergoing diagnostic or therapeutic knee arthroscopy. Human knee synovium (n = 5) was collected during total knee replacement, and a suspended culture was performed to assess the effect of the STEM device on ongoing MSC release. Colony forming unit–fibroblastic assays were used to determine the number of MSCs. Additionally, cytometric characterization of stromal and immune cells and chondrogenesis differentiation assay were performed without culture expansion. Filtered platelet concentrates were prepared using the HemaTrate system. Results: After STEM device use, a significant increase was evident in SF-MSCs ( P = .03) and synovial fluid–resident synovial tissue microfragments ( P = .03). In vitro–suspended synovium released significantly more MSCs following STEM device use than nonstimulated synovium ( P = .01). The STEM device–released total cellular fraction produced greater in vitro chondrogenesis with significantly more glycosaminoglycans (GAGs; P < .0001) when compared with non–STEM device synovial fluid material. Nonexpanded SF-MSCs and SF-microfragments combined with autologous filtered platelet concentrate produced significantly more GAGs than the complete chondrogenic media ( P < .0001). The STEM device–mobilized cells contained more M2 macrophage cells and fewer M1 cells. Conclusion: Non–culture expanded SF-MSCs and SF-microfragments had the potential to undergo chondrogenesis without culture expansion, which can be augmented using the STEM device with increased MSC release from manipulated synovium for several days. Although preliminary, these findings offer proof of concept toward manipulation of the knee joint environment to facilitate endogenous repair responses. Clinical Relevance: Although numbers were small, this study highlights 3 factors relevant to 1-stage joint repair using the STEM device: increased SF-MSCs and SF-microfragments and prolonged synovial release of MSCs. Joint repair strategies involving endogenous MSCs for cartilage repair without the need for culture expansion in a 1-stage procedure may be possible.


Author(s):  
Arvind Gandra

<p class="abstract"><strong>Background:</strong> Patients presenting with knee joint disorders are subjected to variety of investigations which are often inconclusive. Instead if they are subjected for synovial fluid analysis, they will be benefited. The objective of the study was to study synovial fluid analysis among patients with different types of knee joint disorders at a tertiary care hospital.</p><p class="abstract"><strong>Methods:</strong> A hospital based cross sectional study was carried out among 30 patients attending the outpatient Department of Orthopedics and suffering from knee joint pain of either left or right or both the sides. Present study was carried out over a period of two years from January 2011 to December 2012 at Department of Orthopedics, Global Hospitals, Secunderabad. All patients were examined in detail and subjected to all necessary investigations.<strong></strong></p><p class="abstract"><strong>Results:</strong> Males were more than females. The most common joint disease in the study population was tubercular synovitis in 20% of the cases. The most common condition among males was osteoarthritis while there was no such case in females. Rheumatoid arthritis was most common in females while there was no such case in males. Polymorphs were seen in all cases except osteoarthritis and villonodular synovitis. On biochemical analysis of synovial fluid it was found that gouty arthritis did not have proteins. Proteins were minimum in the synovial fluid in case of osteoarthritis while maximum range was found in cases of tubercular arthritis and rheumatoid arthritis.</p><p class="abstract"><strong>Conclusions:</strong> Synovial fluid analysis is very important to understand the etiopathogenesis of knee joint diseases. Our study showed that synovial fluid of the knee joint analysis was very informative in the diagnosis and proper management of the patients presenting with knee joint disorders.</p>


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