Low central sensitisation inventory score is associated with better post-operative outcomes of osteotomy around the knee.

PURPOSE: The purpose of this study was to investigate the potential association between central sensitisation inventory (CSI) scores and post-operative patient-reported outcomes (PROs) in patients underwent osteotomy around the knee (OAK), with a CSI cut-off score specific for knee osteoarthritis. METHODS: CSI scores were collected from 173 patients who underwent OAK, along with their knee injury and osteoarthritis outcome score (KOOS) and pain numeric rating scale (NRS) scores. Patients were divided into high-CSI score group and low-CSI score group with a cut-off score of 17. Multivariate linear regression was performed to test the association between CSI scores and post-operative outcomes. Pre-surgery KOOS and NRS scores and the rate of attainment of minimal clinically important difference (MCID) of KOOS scores was analysed as secondary outcomes. RESULTS: Low-CSI score group had significantly higher post-operative KOOS scores and lower pain NRS scores compared to the high-CSI score group (< p = 0.01) after adjusting for confounding factors. For pre-operative scores, only the KOOS-Symptom score was significantly different between the groups (64.7 ± 20.1 when CSI < 17 vs.55.1 ± 19.7 when CSI ≥ 17; p = 0.008). The low-CSI score group had significantly higher MCID achievement rates of KOOS-Pain, Symptom, and ADL than the high-CSI score group (86% vs. 68%; 74% vs. 55%; 86% vs. 67%, respectively; P < 0.05). CONCLUSIONS: This study established an association between post-operative CSI scores ≥ 17 and poorer outcomes following OAK, highlighting the potential value of the CSI in identifying patients in need of more comprehensive peri-operative pain management. LEVEL OF EVIDENCE: Level III. Retrospective comparative study.

Morphological analysis of three-dimensional MR images of patellofemoral joints in asymptomatic subjects.

The existing methods for analyzing patellofemoral (PF) osteoarthritis (OA) are limited. Our purpose was to clarify the frequency, localization, and morphological progression of PFOA by observing three-dimensional (3D) magnetic resonance (MR) images from a cohort population. The subjects were 561 patients aged 30-79 years from the Kanagawa Knee Study who had not visited a hospital for more than three consecutive months for knee symptoms. MR images of the PF joints, separated into the medial and lateral types, were presented in order of the highest to lowest patella cartilage area ratios. Cartilage defects in the patella were detected in 37 subjects (6.6%). Medial lesions (4.6%) were significantly more frequent than lateral lesions (2.0%) (p < 0.01). For both medial and lateral lesions, the patellar cartilage defects were divided into confined and unconfined types. The 3D MR images of the PF joint showed that the patellar cartilage defect occurred along each ridge of the femoral trochlea. The 3D MR images revealed a 6.6% prevalence of patellar cartilage defects, higher in the medial than lateral regions. The 3D MR images can easily determine PF morphology and cartilage defect location, making them useful in understanding the pathophysiology and etiology of PFOA.

Decision regret following opening wedge high tibial osteotomy: Older age as a risk factor.

BACKGROUND: Understanding risk factors that can predict decision regret after surgical procedures can potentially increase the quality of patient decision making and reduce decision regret after opening wedge high tibial osteotomy (OWHTO). The purpose of the present study was to identify the risk factors that predict the likelihood of decision regret after OWHTO. METHOD: Questionnaires were administered to 98 eligible OWHTO recipients more than one year post-operatively. They answered "Yes" or "No" to the question "Would you go for the same choice (OWHTO) if you had to do it over again?" Univariate and multivariate logistic regression analyses were conducted using the decision regret questionnaire as the dependent variable against patient characteristics and surgery related factors. A receiver operating characteristic curve and area under the curve were constructed and calculated for age at surgery. Cut-off values were determined using the Youden principle and receiver operating characteristic curves. RESULTS: Among the 98 respondents, 18 (18%) reported regretting their decision. Older age at surgery was the only predictive risk factor for decision regret (P < 0.01). The area under the curve for the model using age to predict failure was 0.722. The cut-off value was 71 years. Patients aged 71 years or more had a 7.841 odds ratio for decision regret (P < 0.01). CONCLUSIONS: Older age emerged as a predictive risk factor for decision regret after OWHTO. Patients aged 71 years or older had a higher decision regret rate after OWHTO than younger patients and should more carefully weigh the suitability of OWHTO against other options.

Association of Infrapatellar Fat Pad Fibrosis at 3 Months After ACL Reconstruction With Short-term Clinical Outcomes and Inflammatory Cytokine Levels in the Synovial Fluid.

Background: Infrapatellar fat pad (IFP) fibrosis is reportedly associated with anterior knee pain and the progression of patellofemoral osteoarthritis after anterior cruciate ligament reconstruction (ACLR). However, causes of IFP fibrosis after ACLR have not been sufficiently investigated. Purpose: To compare the descriptive characteristics, clinical outcomes, and inflammatory cytokine levels in the synovial fluid between patients who underwent ACLR with versus without severe IFP fibrosis. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent primary ACLR using autologous hamstring tendon were divided into 2 groups based on magnetic resonance imaging IFP fibrosis scoring (grades 0-5) at 3 months after surgery: the severe fibrosis group (grades 4 and 5) and mild fibrosis group (grades 0-3). Synovial fluid was aspirated on postoperative day 3 or 4 to measure inflammatory cytokine levels. Patient characteristics, clinical outcomes at 3 and 12 months after surgery, and inflammatory cytokine (interleukin [IL]-1ß, IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-α, and interferon-γ) levels were compared between the groups. Results: Of the 36 patients included, 7 were allocated to the severe fibrosis group and 29 were allocated to the mild fibrosis group. The severe fibrosis group had a significantly longer operation time (153.0 vs 116.5 minutes for mild fibrosis; P = .007). Compared with the mild fibrosis group, the severe fibrosis group had greater pain during stair climbing (2.0 vs 0.7; P = .01) and a lower extension muscle strength ratio (operated/healthy side, 52.9% vs 76.1%; P < .001) at 3 months, and the severe fibrosis group had a lower Lysholm score (93.7 vs 97.3; P = .026) and greater knee extension (0.3° vs 1.9°; P = .043) and flexion angle restriction (142.9° vs 149.0°; P = .013) at 12 months. The severe fibrosis group demonstrated higher IL-1ß (2.6 vs 1.4 pg/mL; P = .022), IL-6 (2.0 vs 1.1 ng/mL; P = .029), and interferon-γ levels (11.3 vs 4.0 pg/mL; P = .044). Conclusion: Severe IFP fibrosis was associated with a longer operation time, higher inflammatory cytokine level in the synovial fluid, and worse clinical outcomes at 3 and 12 months after ACLR.

Augmentation of a Nonanatomical Repair of a Medial Meniscus Posterior Root Tear With Centralization Using Three Knotless Anchors May Be Associated With Less Meniscal Extrusion and Better Compressive Load Distribution in Mid-Flexion Compared With Non-Anatomical Root Repair Alone in a Porcine Knee Model.

PURPOSE: To investigate the biomechanics of the centralization augmentation using knotless soft anchors to a nonanatomical transtibial pull-out root repair in a porcine medial meniscus posterior root tear (MMPRT) model. METHODS: Porcine knee joints (N = 10) were used to perform one of the following procedures: (1) intact; (2) MMPRT; (3) nonanatomical root repair; (4) nonanatomical root repair with centralization using 2 anchors: anchors were inserted at the posterior medial collateral ligament (MCL) border and 10 mm anterior to the posterior MCL border; and (5) nonanatomical root repair with centralization using 3 anchors: another anchor was placed 10 mm posterior to the posterior MCL border. Contact area on the medial meniscus (MM), contact pressure in the MM and tibial cartilage, and MM extrusion were evaluated at 30°, 45°, 60°, and 90° knee flexions under 200 N compressive force. RESULTS: MM extrusion at the posterior MCL border was significantly reduced after root repair with centralization using 3 anchors than after root repair alone at 30° (-0.063 mm vs 1.5 mm, P = .017), 45° (0.21 mm vs 1.7 mm, P = .018), and 60° (0.78 mm vs 2.3 mm, P = .019). There were no significant differences in MM extrusion between the root repair alone and root repair with centralization using 2 anchors at all flexion angles. The contact area in the middle and posterior MM was significantly greater after centralization with 3 anchors than after root repair alone at all flexion angles (except the posterior MM at 90°). The mean contact pressure in the tibial cartilage was significantly lower after centralization with 3 anchors than after root repair at all angles. CONCLUSIONS: Augmentation of a nonanatomical repair of a medial meniscus posterior root tear with centralization using three knotless anchors may be associated with less meniscal extrusion and better compressive load distribution between 30° and 60° flexion compared with nonanatomical root repair alone in a porcine model. CLINICAL RELEVANCE: This biomechanical study at time zero suggests that the addition of centralization using 3 knotless anchors may reduce MM extrusion and restore the load-distributing function of the MM.

Autologous Synovial Mesenchymal Stem Cell Transplantation Suppresses Inflammation Caused by Synovial Harvesting and Promotes Healing in a Micro Minipig Repaired Meniscus Model.

PURPOSE: Allogeneic synovial mesenchymal stem cells (MSCs) effectively promote meniscus healing in micro minipigs. We investigated the effect of autologous synovial MSC transplantation on meniscus healing in a micro minipig model of meniscus repair showing synovitis after synovial harvesting. MATERIALS AND METHODS: Synovium was harvested from the left knee of the micro minipigs after arthrotomy and used to prepare synovial MSCs. The left medial meniscus in the avascular region was injured, repaired, and transplanted with synovial MSCs. First, synovitis was compared after 6 weeks in knees with and without synovial harvesting. Second, the repaired meniscus was compared for the autologous MSC group and the control group (in which synovium was harvested but MSCs were not transplanted) 4 weeks after transplantation. RESULTS: Synovitis was more severe in knees subjected to synovium harvesting than in knees not subjected to harvesting. Menisci treated with autologous MSCs showed no red granulation at the tear of the meniscus, but menisci not treated with MSCS showed red granulation. Macroscopic scores, inflammatory cell infiltration scores, and matrix scores assessed by toluidine blue staining were all significantly better in the autologous MSC group than in the control group without MSCs (n = 6). CONCLUSION: Autologous synovial MSC transplantation suppressed the inflammation caused by synovial harvesting in micro minipigs and promoted healing of the repaired meniscus.

Association between knee cartilage thickness determined by magnetic resonance imaging three-dimensional analysis and the International Cartilage Repair Society (ICRS) arthroscopic grade.

BACKGROUND: The purpose of this study was to retrospectively investigate whether the average cartilage thickness calculated by magnetic resonance imaging (MRI) three-dimensional (3D) analysis system was correlated with the International Cartilage Repair Society (ICRS) grade at each subregion, as a representative scoring for arthroscopic evaluation. METHODS: The subjects were 102 patients who underwent arthroscopy for meniscus repair or high tibial osteotomy for medial osteoarthritis of the knee. Cartilage lesions were arthroscopically quantified according to the ICRS grade at each subregion. Fluoroscopy was used to compare the subregions on arthroscopic evaluation with subregions on MRI. The average cartilage thickness at each subregion was also automatically calculated from MRI data using our 3D analysis system. The association between ICRS grade and the average cartilage thickness at 18 subregions in the medial femoral and medial tibial regions was evaluated using Spearman's rank correlation coefficient. RESULTS: Examination of the fluoroscopic images revealed that the posterior subregions in the medial femoral region did not match the position between arthroscopy and MRI; therefore, those three subregions were excluded. In the medial femoral region, the ICRS grade correlated moderately with cartilage thickness at five subregions and weakly at one subregion. In the medial tibial region, the ICRS grade correlated moderately with cartilage thickness at four subregions and weakly at one subregion, but it did not correlate at the other four subregions. CONCLUSION: The average cartilage thickness determined by MRI 3D analysis correlated with arthroscopic grade at 11 of 15 subregions in the medial femoral and tibial regions.

Simultaneous bilateral total knee arthroplasty is safe and effective for patients in different ages.

BACKGROUND: Simultaneous bilateral total knee arthroplasty is considered beneficial for patients with bilateral end-stage knee osteoarthritis, even though there could be potential postoperative complications. Presently, there is a paucity of evidence of the efficacy and safety of SB-TKA for elderly patients. This study aimed to compare the clinical outcomes of simultaneous bilateral total knee arthroplasty by different age groups. METHODS: A total of 216 knees of 108 patients, who underwent simultaneous bilateral total knee arthroplasty for osteoarthritis at our hospital between April 2015 and September 2018, were divided into three groups based on age: 60s (44 knees), 70s (106 knees), and 80s (66 knees). Perioperative data and postoperative clinical outcomes 1 year after surgery were compared between the age groups. RESULTS: The patients in the Group 60s were characterized by a higher body mass index (BMI) (P < 0.01), a lower pre-operative knee function score (P < 0.01), longer operation time (P < 0.01), greater intra-operative (P < 0.01), and postoperative bleeding (P = 0.026). No significant difference was found in terms of occurrence of various postoperative complications, although deep vein thrombosis and delirium occurred slightly more frequently in the Group 70s and the Group 80s than in the Group 60s group. The Knee Society Knee Score, a function score, and patient satisfaction scores were significantly improved in all groups 1 year after surgery. Moreover, these indexes of clinical outcomes were similar among the three groups. CONCLUSION: Performing simultaneous bilateral total knee arthroplasty in 80s patients was found to be as safe and effective as in the 60s and 70s patients. LEVEL OF EVIDENCE: 3 (A retrospective cohort study).

Comparison of Clinical Outcomes after Revision Anterior Cruciate Ligament Reconstruction using a Bone-patellar Tendon-bone Autograft and that Using a Double-Bundle Hamstring Tendon Autograft.

PURPOSE: The purpose of this study was to compare clinical outcomes between revision anterior cruciate ligament reconstruction (ACLR) using a bone-patellar tendon-bone (BPTB) autograft and that using a double-bundle hamstring tendon (HT) autograft. METHODS: Consecutive cases of revision ACLRs were reviewed. The Lysholm knee scale and Knee Osteoarthritis Outcome Score (KOOS) were recorded at the final follow-up. The pivot shift test, Lachman test, and anterior knee laxity measurement using an arthrometer were evaluated before revision ACLR and at final follow-up. Contralateral knee laxity was also evaluated, and side-to-side differences noted. The Lysholm knee scale, KOOS, the pivot shift test, Lachman test, and anterior knee laxity were compared between HT versus BPTB autograft recipient groups using the Mann-Whitney test or the t-test. RESULTS: Forty-one patients who underwent revision ACLR and followed up for at least 2 years were included. The graft source was a BPTB autograft in 23 patients (BPTB group) and a double-bundle HT autograft in 18 patients (HT group). The mean postoperative follow-up period was 44 ± 28 months in the BPTB group and 36 ± 18 in the HT group (p = 0.38). The HT group had significantly higher KOOS in the pain subscale (less pain) than the BPTB group at the final follow-up (BPTB group 84.2 vs. HT group 94.4; p = 0.02). The BPTB group showed significantly smaller side-to-side difference in anterior knee laxity (superior stability) than the HT group (0.3 vs. 2.6 mm; p < 0.01). The percentage of patients with residual anterior knee laxity in the BPTB group was significantly lower than that in the HT group (9.5% vs. 46.7%; odds ratio, 8.3; p = 0.02). STUDY DESIGN: This was a level 3 retrospective study. CONCLUSION: Revision ACLR with a BPTB autograft was associated with superior results regarding restoration of knee joint stability as compared with that with a double-bundle HT autograft, whereas double-bundle HT autograft was superior to BPTB autograft in terms of patient-reported outcomes of pain. The rest of the patient-reported outcomes were equal between the two groups.

Mid-term clinical outcomes of a posterior stabilized total knee prosthesis for Japanese patients: A minimum follow-up of 5 years.

BACKGROUND: A high-flexion posterior-stabilized total knee prosthesis has been developed for the Asian population. The component design was based on computed tomography images of Japanese osteoarthritic knees. The femoral component is composed of zirconia ceramics, which exhibit low friction and high durability. The present study aimed to evaluate the mid-term clinical outcomes of this implant. METHODS: This study included 334 knees of 210 patients who underwent primary total knee arthroplasty with this implant at our hospital between October 2010 and December 2014. The patients comprised 28 men and 172 women with an average age of 73 years. The average follow-up period was 5.9 years, and the follow-up rate was 71.1%. Clinical outcomes were assessed using the Knee Society scoring system, 2011 Knee Society questionnaire, and Knee Injury and Osteoarthritis Outcome Score. Kaplan-Meier survivorship analysis was performed to determine the cumulative prosthesis survival rate. RESULTS: In terms of clinical outcomes at the final follow-up, the average ranges of motion were -2.0 in extension and 126.7 in flexion. The Knee Society knee and function scores were 94.2% and 72.6%, respectively. With revision surgery or radiographic failure for any reason as the endpoint, the survival rates at 5 and 9 years were 98.2% and 95.5%, respectively. The most common reason for revision surgery or radiological failure was aseptic loosening. CONCLUSIONS: Despite several revision cases mainly due to aseptic loosening, the present study found that this new high-flexion posterior-stabilized total knee arthroplasty prosthesis design showed comparable results for Asian populations with other PS prosthesis. LEVELS OF EVIDENCE: Level Ⅱ (Prospective cohort study).

Comparison of adhesion of thawed and cultured synovial mesenchymal stem cells to the porcine meniscus and the relevance of cell surface microspikes.

BACKGROUND: Placement of a cultured synovial mesenchymal stem cell (MSC) suspension on a repaired meniscus for 10 min accelerated meniscus repair. Upon placement of the MSC suspension on the meniscus, microspikes projecting from the MSC surface trap meniscus fibers and promote MSC adhesion. Thawed cryopreserved MSCs are preferred materials for meniscus repair, as they can be transplanted without additional culture. However, the adhesion ability of thawed cryopreserved MSCs is unknown. Here, we compared the proportion of cultured versus thawed MSCs adhering to a porcine meniscus immediately and 10 min after placement. We also investigated the relationship between adhesion and the number of microspikes on the synovial MSCs. METHODS: Synovial MSCs were prepared from the knees of four donors with osteoarthritis. The "cultured MSCs" were thawed MSCs that were re-cultured and suspended in PBS for transplantation. A similarly prepared suspension was cryopreserved, thawed again, suspended in PBS, and used without further culture as the "thawed MSCs." MSCs with at least three microspikes in SEM images were defined as microspike-positive MSCs. Porcine meniscus surfaces were abraded, cut into a cylindrical shape, and treated with MSC suspension. Non-adherent cells were counted immediately and again 10 min after placement to calculate the adhesion proportion. RESULTS: The proportion of microspike-positive MSCs was significantly higher in thawed (53 ± 3%) than in cultured (28 ± 5%) MSC suspensions. MSC adhesion to the meniscus was significantly better for the thawed than for the cultured MSC suspensions immediately after placement on the meniscus, but no differences were detected after 10 min. The proportion of MSCs with microspikes in the cell suspension was significantly correlated with the proportion of adhered MSCs immediately after the placement, but not 10 min later. Addition of FBS to the cryopreservation medium promoted a concentration-dependent increase in the proportion of microspike-positive cells. CONCLUSIONS: Thawed MSCs adhered better than cultured MSCs immediately after placement, but adhesion was similar for both MSC preparations after 10 min. Immediately after placement, the presence of microspikes was associated with better adhesion of synovial MSCs to the meniscus.

Human synovial mesenchymal stem cells show time-dependent morphological changes and increased adhesion to degenerated porcine cartilage.

The possibility that mesenchymal stem cells (MSCs) can adhere to partial defects or degenerative areas in cartilage remains to be established. The purposes of the present study were to verify the adhesion of synovial MSCs to degenerated cartilage, the time course of that adhesion, and the morphological changes that MSCs might undergo during the adhesion process. The surface of pig cartilage was abraded, and a human synovial MSC suspension was placed on the abraded surface. The proportion/number of MSCs that adhered to the cartilage was quantified by counting non-adhered MSCs, measuring the fluorescence intensity of DiI-labeled MSCs, and scanning electron microscopy (SEM) observations. The presence of microspikes or pseudopodia on the MSCs that adhered to the cartilage was also evaluated. SEM confirmed the adhesion of synovial MSCs to degenerated cartilage. The three independent quantification methods confirmed increases in the proportion/number of adhered MSCs within 10 s of placement and over time up to 24 h. The MSCs that adhered at 10 s had a high proportion of microspikes, whereas those that adhered after 1 h had that of pseudopodia. MSCs showed time-dependent morphological changes and increased adhesion to degenerated cartilage after placement of the human synovial MSC suspension.

Risk Factors Affecting Return to Sports and Patient-Reported Outcomes After Opening-Wedge High Tibial Osteotomy in Active Patients.

Background: Although opening-wedge high tibial osteotomy (OWHTO) is favored for active patients who expect to return to sports, there is still a lack of robust evidence for factors affecting their recovery. Purpose: To identify (1) risk factors leading to a decreased level of return to preoperative sports after OWHTO and (2) patient characteristics and intraoperative factors influencing patient-reported outcomes after return to sports. Study Design: Case-control study; Level of evidence, 3. Methods: Included were 69 patients who underwent OWHTO and who expected to return to their preoperative level of sports, measured as a Tegner activity level ≥2. All included patients had a minimum of 1 year of follow-up data. Logistic regression analyses were performed to assess the effect of independent variables on the level of return to preoperative sports after surgery; the independent variables were age, sex, body mass index, preoperative Tegner score, preoperative Kellgren-Lawrence grade, preoperative percentage of mechanical axis (%MA), opening gap width, concomitant meniscal treatment, postoperative %MA, postoperative medial proximal tibial angle (MPTA), and postoperative posterior tibial slope. Univariate and multiple regression analyses were performed to assess for influencing factors on postoperative International Knee Documentation Committee (IKDC) subjective scores in patients who were able to return to sports. Results: Of the 69 patients, 51 (73.9%) returned to sports after OWHTO. High preoperative Tegner scores were statistically associated with a decrease in return to sports (odds ratio, 1.494; P = .033). Multiple regression analysis (n = 46 patients) identified that a higher postoperative MPTA was associated with a decreased IKDC subjective score after return to sports (r = -0.345; P = .019). Conclusion: Higher postoperative MPTA was associated with the worsening of patient-reported outcomes among those patients who did return to their preoperative sports after OWHTO. Also, participation in high-activity sports was confirmed to be a significant risk factor for a decreased rate of return to preoperative sports. These findings can support preoperative planning and intraoperative decision making, particularly for active patients.

Safety of using cultured cells with trisomy 7 in cell therapy for treating osteoarthritis.

Cell therapy is a promising alternative treatment approach currently under study for osteoarthritis (OA), the most common chronic musculoskeletal disease. However, the mesenchymal stem cells (MSCs) used in cell therapy to treat OA are usually expanded in vitro to obtain sufficient numbers for transplantation, and their safety has not been fully assessed from multiple perspectives. Analysis of karyotypic abnormalities, in particular, is important to ensure the safety of cells; however, chromosomal mutations may also occur during the cell-expansion process. In addition, there have been many reports showing chromosome abnormalities, mainly trisomy 7, in the cartilage and synovium of patients with OA as well as in normal tissues. The suitability of cells with these karyotypic abnormalities as cells for cell therapy has not been evaluated. Recently, we assessed the safety of using cells with trisomy 7 from the osteoarthritic joint of a patient for transplantation, and we followed up with the patient for 5 years. This study showed analysis for copy number variant and whole-genome sequencing, compared with blood DNA from the same patient. We did not find any abnormalities in the genes regardless of trisomy 7. No side effects were observed for at least 5 years in the human clinical study. This suggests that the transplantation of cultured cells with trisomy 7 isolated from an osteoarthritic joint and transplanted into the osteoarthritic joints of the same person is not expected to cause serious adverse events. However, it is unclear what problems may arise in the case of allogeneic transplantation. Different types of risks will also exist depending on other transplantation routes, such as localization to the knee-joint only or circulation inflow and lung entrapment. In addition, since the cause of trisomy 7 occurrence remains unclear, it is necessary to clarify the mechanism of trisomy 7 in OA to perform cell therapy for OA patients in a safe manner.

Cell membrane fluidity and ROS resistance define DMSO tolerance of cryopreserved synovial MSCs and HUVECs.

OBJECTIVES: Synovial mesenchymal stem cells (MSCs) have high freeze-thaw tolerance, whereas human umbilical vein endothelial cells (HUVECs) have low freezing tolerance. The differences in cell type-specific freeze-thaw tolerance and the mechanisms involved are unclear. This study thus aimed to identify the biological and physical factors involved in the differences in freeze-thaw tolerance between MSCs and HUVECs. MATERIALS AND METHODS: For biological analysis, MSC and HUVEC viability after freeze-thawing and alteration of gene expression in response to dimethyl sulfoxide (DMSO, a cryoprotectant) were quantitatively evaluated. For physical analysis, the cell membrane fluidity of MSCs and HUVECs before and after DMSO addition was assessed using a histogram for generalized polarization frequency. RESULTS: HUVECs showed lower live cell rates and higher gene expression alteration related to extracellular vesicles in response to DMSO than MSCs. Fluidity measurements revealed that the HUVEC membrane was highly fluidic and sensitive to DMSO compared to that of MSCs. Addition of CAY10566, an inhibitor of stearoyl-coA desaturase (SCD1) that produces highly fluidic desaturated fatty acids, decreased the fluidity of HUVECs and increased their tolerance to DMSO. The combination of CAY10566 and antioxidant glutathione (GSH) treatment improved HUVEC viability from 57 to 69%. Membrane fluidity alteration may thus contribute to pore-induced DMSO influx into the cytoplasm and reactive oxygen species production, leading to greater cytotoxicity in HUVECs, which have low antioxidant capacity. CONCLUSIONS: Differences in freeze-thaw tolerance originate from differences in the cell membranes with respect to fluidity and antioxidant capacity. These findings provide a basis for analyzing cell biology and membrane-physics to establish appropriate long-term preservation methods aimed at promoting transplantation therapies.

Surgical Repair of Symptomatic Wrisberg Variant Discoid Lateral Mensicus with Pull-Out Repair and Capsulodesis.

Wrisberg variant discoid lateral meniscus (DLM) is a congenital anatomic variation of the meniscus in the knee joint, which is an uncommon type of the DLM. We present a surgical technique in a case of symptomatic Wrisberg variant DLM. To improve the instability due to the lack of the posterior attachment of meniscotibial ligament, the posterior portion of DLM was attached to the insertion site of normal LM posterior root using pull-out repair technique. In addition, a longitudinal tear from the anterior to the middle portion of DLM was repaired with outside-in and inside-out techniques. Finally, a capsulodesis using knotless anchors was performed from outside of the joint to prevent the meniscus extrusion after the surgery. Knee symptoms such as pain, catching, and ROM restriction disappeared at 3 months after the surgery. Postoperative magnetic resonance imaging showed a slightly sharpened shape of the DLM, and the attachment of the posterior portion of the DLM was observed. Longitudinal tear of the DLM was healed without cleavage. This procedure is useful to improve the symptoms of the knee joint with Wrisberg variant DLM and to preserve the function of the meniscus.

Yields of mesenchymal stromal cells from synovial fluid reflect those from synovium in patients with rheumatoid arthritis.

The yield of primary synovial mesenchymal stromal cells (MSCs) from synovium of patients with rheumatoid arthritis (RA) is highly variable, but cell transplantation therapy with autologous synovial MSCs requires accurate prediction of the synovial MSC yield per synovium weight. Here, we determined whether the yield of synovial fluid MSCs might predict the ultimate yield of primary MSCs from the synovium of RA knees. Synovial fluid and synovium were harvested during total knee arthroplasty from the knee joints of 10 patients with RA. Synovial fluid (1.5 mL) was diluted fourfold and plated equally into six 60 cm2 dishes. Nucleated cells from digested synovium were similarly plated at 1 × 104 cells in 6 dishes. All dishes were cultured for 14 days and analyzed for MSC yields and properties, including in vitro chondrogenesis. The cultured synovial cell number was correlated with the cultured synovial fluid cell number (n = 10, R2 = 0.64, p < 0.01). Synovial fluid cells formed cell colonies and showed MSC-like surface epitopes and multi-differentiation potential. However, the cartilage pellet weight indicated a greater chondrogenic potential of the synovial MSCs (n = 8). The primary MSC yields from synovial fluid and synovium were correlated, indicating that the synovial fluid MSC yield can predict the ultimate synovial MSC yield.

Second-look arthroscopy after meniscus repair and synovial mesenchymal stem cell transplantation to treat degenerative flaps and radial tears of the medial meniscus: A case report.

BACKGROUND: The purpose of this study was to compare arthroscopic findings of a degenerative flap and radial tear of the medial meniscus (MM) before and one year after treatment by meniscus repair and synovial mesenchymal stem cell (MSC) transplantation. METHODS: Patients with a degenerative flap and radial MM tear that would generally be treated by meniscectomy were included. The patients ranged in age from 45 to 62 years and all underwent meniscus repair and synovium harvest at time 0. The digested synovium was cultured with autologous serum for 12 days, and an average of 4 × 107 MSCs were transplanted at two weeks. A second-look arthroscopy was performed at 52 weeks (n = 6). The average duration of symptoms was 24 months. For flap tears, arthroscopic findings were quantified in terms of the presence, stability, and smoothness of the meniscus at each zone and area. The Lysholm score was evaluated throughout the 52 week follow-up. RESULTS: Four patients with MM flap tears showed deficiencies in the central area at the posterior junctional zone before treatment, but this zone was completely restored to a stable and smooth condition in two patients and partially restored in the other two patients. The arthroscopy score for a flap tear at the central area of the posterior junctional zone was 0.3 ± 0.5 before treatment and 4.3 ± 2.1 after treatment. The score was significantly higher after treatment (p < 0.05, n = 4). The original radial MM tears in two patients were healed one year after treatment. Lysholm scores were significantly higher at 4 and 52 weeks after treatment than before treatment (n = 6). CONCLUSIONS: Arthroscopic findings for a degenerative flap and radial tear of the MM were improved at the central area of the posterior junctional zone one year after meniscus repair and MSC transplantation.

Transplantation of human autologous synovial mesenchymal stem cells with trisomy 7 into the knee joint and 5 years of follow-up.

Mesenchymal stem cells (MSCs) can show trisomy 7; however, the safety of these cells has not been fully investigated. The purposes of this study were to determine the ratio of patients whose synovial MSCs were transplanted clinically, to intensively investigate MSCs with trisomy 7 from a safety perspective, and to follow up the patients for 5 years after transplantation. Synovial MSCs at passage 0 were transplanted into a knee for degenerative meniscus tears in 10 patients, and the patients were checked at 5 years. The synovial MSCs were evaluated at passages 0 to 15 by G-bands and digital karyotyping, and trisomy 7 was found in 3 of 10 patients. In those three patients, 5% to 10% of the synovial MSCs showed trisomy 7. The mRNA expressions of representative oncogenes and genes on chromosome 7 did not differ between MSCs with and without trisomy 7. Whole-genome sequencing and DNA methylation analysis showed similar results for MSCs with and without trisomy 7. Transplantation of human synovial MSCs with trisomy 7 into eight mouse knees did not result in tumor formation under the skin or in the knees after 8 weeks in any mouse, whereas transplanted HT1080 cells formed tumors. In vitro chondrogenic potentials were similar between MSCs with and without trisomy 7. Five-year follow-ups revealed no serious adverse events in all 10 human patients, including 3 who had received MSCs with trisomy 7. Overall, our findings indicated that synovial MSCs with trisomy 7 were comparable with MSCs without trisomy 7 from a safety perspective.

Clinical outcomes of two-stage revision total knee arthroplasty in infected cases with antibiotic-loaded cement spacers produced using a handmade silicone mold.

PURPOSE: This study assessed the clinical outcomes of periprosthetic joint infection patients who underwent two-stage revision total knee arthroplasty with antibiotic-loaded cement spacers fabricated using a handmade silicone mold. MATERIALS AND METHODS: This study included seven patients (average age 77 years, average follow-up time 54 months) who underwent surgery at our hospital between 2009 and 2013. Clinical outcomes including knee scores, function scores, knee range of motion, and walking ability at the final observation, period from the primary total knee arthroplasty to implant removal, period from implant removal to revision total knee arthroplasty, and follow-up period after revision total knee arthroplasty were investigated. RESULTS: At the final follow-up, the average knee range of motion was 99°, with no significant differences at each stage; average knee and function scores were 84 and 77, respectively. With cement spacers, five patients were able to walk with a t-cane. No recurrence of infection was observed. CONCLUSIONS: The clinical outcomes of the current case series demonstrated good knee function with preserved walking ability, without any recurrence of periprosthetic joint infection. This study suggests that using a handmade silicone mold could be an effective option for periprosthetic joint infection after a total knee arthroplasty.