A novel cell source for therapy of knee osteoarthritis using atelocollagen microsphere-adhered adipose-derived stem cells: Impact of synovial fluid exposure on cell activity.

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 2D-cultured 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.

Septic Arthritis of Cervical Spine Facet Joints: A Case Report and Review of Imaging.

BACKGROUND Septic arthritis of the facet joint (SAFJ) has been considered a rare type of spinal infection. However, because of the aging of the population, the increase in compromised hosts, and the increase in MRI use in recent years, the number of reports has been increasing. We report the clinical progress of a rare case of septic arthritis of the cervical facet joint (SACFJ) with some imaging considerations, and we compare our findings with existing reports of SACFJ. CASE REPORT A 73-year-old Japanese woman presented with fever, paralytic symptoms, and paresthesia of the upper limbs. Here, we report a case of SACFJ in which MRI findings allowed early diagnosis, and a favorable course was obtained by conservative treatment with antibiotics. Although MRI performed 93 days after the initiation of treatment showed a slight residual signal change in the facet joints, no symptoms had recurred by the sixth month after hospital discharge. CONCLUSIONS If a patient develops neurological symptoms such as paralysis with fever and increased inflammatory response, the physician must consider the possibility of pyogenic spondylitis, including SACFJ, and order an MRI. Epidural abscess is almost inevitable in SACFJ, and surgical treatment, including abscess drainage, is required if spinal cord or paralytic symptoms progress. For patients with SACFJ, as well as pyogenic spondylitis, MRI may not be useful in determining treatment efficacy.

A Case of Axillary Web Syndrome Caused by Venous Blood Sampling.

Axillary web syndrome (AWS) occurs after breast cancer surgery, sentinel lymph node dissection, or sentinel lymph node biopsy. Here, cord-like structures from the axilla to the forearm limit the range of motion of the shoulder joint and cause pain. Although the etiology is unknown, AWS has been attributed to the blockage of normal lymphatic flow. Here, we report a novel case of AWS after venous blood sampling in a patient. A healthy, 31-year-old male patient experienced pain with a limited range of motion of the shoulder joint the day after venous blood was collected from the left upper extremity for a medical checkup, and he presented to an orthopedic outpatient clinic on the day. Palpation of the axillary region disclosed a cord-like structure in the axillary region of the shoulder joint during abduction, and the patient was diagnosed with AWS. The cord-like structure was noted to be a hypoechogenic luminal structure on ultrasound (US) examination of the axilla, extending from the axilla to below the ulnar cutaneous vein from which the blood was drawn. In patients with pain and a limited range of motion of the shoulder joint, only the shoulder joint is examined during an orthopedic examination. It is important to obtain appropriate physical findings for possible AWS.

Synovial Fluid Derived from Human Knee Osteoarthritis Increases the Viability of Human Adipose-Derived Stem Cells through Upregulation of FOSL1.

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.

A Unique Surgical Case of Ancient Calcified Intravascular Papillary Endothelial Hyperplasia in the Tibia with Knee Joint Osteoarthritis.

BACKGROUND: Intravascular papillary endothelial hyperplasia (IPEH) is a reactive lesion histopathologically characterized by papillary growth of vascular endothelial cells. IPEH is most commonly found in the skin and subcutaneous tissues of the head, neck, and extremities. Furthermore, it has been reported to occur in oral surgery, but its occurrence in bone is extremely rare. CASE PRESENTATION: We present the case of a 77-year-old man with a chief complaint of left knee arthralgia. The knee joint X-ray showed Kellgren-Lawrence grade 4 osteoarthritis and a mass lesion with decreased permeability within the bone in the medial part of the proximal tibia. Computerized tomography (CT) scan of the left knee showed a localized mass in the left proximal tibia with clear margins and granular internal calcification. The preoperative diagnosis was left knee osteoarthritis and a benign tumor of the left proximal tibia (enchondroma or hemangioma). The patient requested surgical treatment, so left total knee arthroplasty (TKA) and resection of the tumor were performed. The pathology revealed a rare intraosseous IPEH with marked calcification. CONCLUSIONS: Since intraosseous IPEH could not be considered from the clinical findings, the pathological diagnosis was the decisive factor. This report showed the world's first case of intraosseous IPEH with marked calcification. Similar to the calcification of intraosseous hemangiomas, we considered the possibility that, in IPEH, the thrombus may fibrosis and organize in concentric circles, causing necrosis at the center and resulting in calcification. TKA was performed on the degenerative knee joint with IPEH, and a good patient outcome was obtained.

A morphological study of adipose-derived stem cell sheets created with temperature-responsive culture dishes using scanning electron microscopy.

Adipose-derived stem cell (ADSC) sheets have potential to be effective in various therapies. In this study, we first demonstrated that a cell sheet composed of human ADSCs could be created using a new temperature-responsive culture dish from the DIC Corporation. The dish can cause detachment of adherent cells due to temperature changes, but a few morphological analyses have evaluated the presence or absence of damage on the detached surface of cell sheet. To characterize our ADSC sheet, we tried to observe the surface of ADSC sheets with scanning electron microscope (SEM) using the ionic liquid, which enables the rapid preparation of samples. No damage was found on the surface of the ADSC sheets on the side that had been in contact with the surface of the culture dishes. In addition, when the transcriptomes of the harvested cell sheets were compared with those of monolayer cultures, no up-regulation of cell death related genes were detected. These results propose that the detachment from temperature-responsive culture dish causes no serious damage on the prepared ADSC sheet. It is also suggested that the SEM with ionic liquids is a useful and rapid method for the analysis of ADSC sheets for therapy.

Evaluation of the Usefulness of Human Adipose-Derived Stem Cell Spheroids Formed Using SphereRing® and the Lethal Damage Sensitivity to Synovial Fluid In Vitro.

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.

Bone ingrowth observed in a cup removed during revision surgery for early dislocation after primary THA: A case report.

INTRODUCTION AND IMPORTANCE: Recently cementless total hip arthroplasty (THA) has shown good long-term results with excellent stability resulted from the porous coating of the implant. A hydroxyapatite-tricalcium phosphate (HA-TCP) coating on the porous surface is expected to promote bone ingrowth and to improve initial fixation of the implant. Here we report a case of bone ingrowth observed in a cup removed during revision surgery for early dislocation, 37 days after primary THA using a porous coating cup with HA-TCP. CASE PRESENTATION: A 61-year-old woman who has bilateral osteoarthritis underwent same-day bilateral THA. Both sides used porous coating cups with HA-TCP. Line-to-line technique and screw fixation were utilized. Anterior dislocation of the left hip occurred on days 27 and 31, and we performed cup revision on day 37 after surgery. We noted bone-like tissue on the posterior surface of the cup and in a vacant screw hole. Bone tissue was also confirmed in pathological findings. CLINICAL DISCUSSION: Studies in animals have confirmed early bone ingrowth about 4 weeks after surgery with HA-TCP coated implants. In humans, the earliest report of bone ingrowth in cups is for a cup without HA-TCP coating, detected 5 weeks after surgery. In the present case, we used a porous coating cup with HA-TCP, and bone ingrowth was confirmed at approximately the same time as for the previous case. CONCLUSION: Early clinical bone ingrowth was confirmed in an HA-TCP coated cup, occurring at about the same time after surgery as in previous reports.