Osteoarthritis (OA) is an irreversible degenerative condition causing bone deformation in the joints and articular cartilage degeneration with chronic pain and impaired movement. Adipose-derived stem cell (ADSC) or crushed adipose tissue injection into the joint cavity reportedly improve knee function and symptoms, including pain. Stem cell spheroids may be promising treatment options due to their anti-inflammatory and enhanced tissue regeneration/repair effects. Herein, to form human ADSC spheroids, we used first SphereRing^® (Fukoku Co., Ltd., Ageo, Japan), a newly developed rotating donut-shaped tube and determined their characteristics by DNA microarray of mRNA analysis. The variable gene expression cluster was then identified and validated by RT-PCR. Gene expression fluctuations were observed, such as COL15A1 and ANGPTL2, related to vascular endothelial cells and angiogenesis, and TNC, involved in tissue formation. In addition, multiplex cytokine analysis in the medium revealed significant cytokines and growth factors production increase of IL-6, IL-10, etc. However, ADSC administration into the joint cavity involves their contact with the synovial fluid (SF). Therefore, we examined how SF collected from OA patient joint cavities affect 2D-culture ADSCs and ADSC spheroids and observed SF induced cell death. ADSC spheroids could become promising OA treatment options, although studying the administration methods and consider their interaction with SF is essential.

Knee osteoarthritis (Knee OA) is an irreversible condition that causes bone deformity and degeneration of the articular cartilage that comprises the joints, resulting in chronic pain and movement disorders. The administration of cultured adipose-derived stem cells (ADSCs) into the knee joint cavity improves the clinical symptoms of Knee OA; however, the effect of synovial fluid (SF) filling the joint cavity on the injected ADSCs remains unclear. In this study, we investigated the effect of adding SF from Knee OA patients to cultured ADSCs prepared for therapeutic use in an environment that mimics the joint cavity. An increase in the viability of ADSCs was observed following the addition of SF. Gene expression profiling of SF-treated ADSCs using DNA microarrays revealed changes in several genes involved in cell survival. Of these genes, we focused on FOSL1, which is involved in the therapeutic effect of ADSCs and the survival and proliferation of cancer stem cells. We confirmed the upregulation of FOSL1 mRNA and protein expression using RT-PCR and western blot analysis, respectively. Next, we knocked down FOSL1 in ADSCs using siRNA and observed a decrease in cell viability, indicating the involvement of FOSL1 in the survival of ADSCs. Interestingly, in the knockdown cells, ADSC viability was also decreased by SF exposure. These results suggest that SF enhances cell viability by upregulating FOSL1 expression in ADSCs. For therapy using cultured ADSCs, the therapeutic effect of ADSCs may be further enhanced if an environment more conducive to the upregulation of FOSL1 expression in ADSCs can be established.

Background/Objectives: Knee osteoarthritis (KOA) is a degenerative joint disease typically managed with conservative treatments, such as anti-inflammatory medications and intra-articular hyaluronic acid injections; however, advanced cases may eventually require surgical intervention. Recently, cooled radiofrequency ablation (CRFA) has emerged as a novel treatment option for alleviating KOA-related pain by temporarily disabling pain-transmitting nerves. This study evaluated the short-term effects of CRFA on pain relief and walking ability in KOA patients, with a specific focus on functional improvements in walking capacity. Methods: This study included 58 patients (71 knees) with KOA who underwent CRFA after experiencing inadequate pain control with conservative treatments. The cohort consisted of 28 men and 30 women, with a mean age of 75.2 years (55–90). Under ultrasound guidance, CRFA was performed on the superior lateral geniculate nerve, superior medial geniculate nerve, and inferior medial geniculate nerve, with each targeted nerve ablated. Pre- and post-procedural evaluations (one month after CRFA) included assessments of visual analog scale (VAS) scores for pain at rest and during walking, range of motion (ROM), knee extensor strength, walking speed, and gait stability. Results: Significant improvements in the mean VAS (rest/walking) and mean walking speed (comfortable/maximum) were observed following CRFA. However, no significant changes were noted in ROM, knee extensor strength, or walking stability. Conclusions: These findings suggest that rehabilitation may be essential to further enhance walking stability. Overall, CRFA appears to be a promising short-term treatment option for reducing VAS pain scores and enhancing walking speed in patients with KOA.

Introduction: Administration of adipose -derived stem cells (ADSCs) into the joint cavity has been shown to alleviate the symptoms of knee osteoarthritis (OA) by releasing exosomes and anti-inflammatory cytokines. However, the therapeutic effect of these cells is limited by their rapid disappearance after administration. Thus, it is necessary to prolong cell survival in the joint cavity. This study aimed to investigate the potential application of ADSCs adhered to atelocollagen microspheres (AMSs) for cell therapy of knee OA. Methods: ADSCs were cultured for 2, 4, and 7 days in AMS suspension or adherent culture dishes. The supernatants were analyzed for IL -10 and exosome secretion via enzyme -linked immunosorbent assay and Nanosight. The effect of AMS was compared with that of adherent -cultured ADSCs (2D -cultured ADSCs) using transcriptome analysis. Moreover, the solubility of AMS and viability of ADSCs were evaluated using synovial fluid (SF) from patients with knee OA. Results: Compared with 2D -cultured ADSCs, AMS-cultured ADSCs exhibited a significant increase in secretion of exosomes and IL -10, and the expression of several genes involved in extracellular matrix and immune regulation were altered. Furthermore, when AMS-cultured ADSCs were cultured in SF from knee OA patients to mimic the intra-articular environment, the SF dissolved the AMSs and released viable ADSCs. In addition, AMS-cultured ADSCs showed significantly higher long-term cell viability than 2Dcultured ADSCs. Conclusion: Increased survival of AMS-adhered ADSCs was observed in the intra-articular environment, and AMSs were found to gradually dissipate. These results suggest that AMS-adhered ADSCs are promising source for cell therapy of knee OA. (c) 2024, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).