Synovial mesenchymal stem cells secrete more lubricin than adipose mesenchymal stem cells after injection into rat osteoarthritis knees.

Intra-articular injection of mesenchymal stem cells (MSCs) is envisioned as a solution for knee osteoarthritis (OA). Although synovial MSCs (SyMSCs) are promising for cartilage regeneration, the clinical choice is usually adipose MSCs (AdMSCs). However, the similarities/differences in the mode of action between SyMSCs and AdMSCs remain unclear. Here, we compared factors secreted by human SyMSCs and AdMSCs after injection into OA knees. Human SyMSCs or AdMSCs were injected into the knees of rat partial meniscectomy models. The next day, the knee joints were collected to analyze the distribution of injected MSCs and transcriptome changes in the human MSCs and rat synovium. Non-injected MSCs were mixed with rat synovium as a control. After injection, no difference was apparent in intra-articular distribution of the SyMSCs or AdMSCs. RNA sequencing demonstrated an enrichment of cytokine-cytokine receptor interaction-related genes in both human SyMSCs and AdMSCs after injection. Differentially expressed genes (DEGs) specific to SyMSCs were associated with cartilage matrix synthesis and homeostasis. PCR analysis of the matrisome-related DEGs showed significantly higher expression of PRG4 in SyMSCs than in AdMSCs after injection. Immunostaining also confirmed a significantly greater expression of lubricin by SyMSCs than by AdMSCs. These findings indicate that SyMSCs will be a more promising treatment for OA.

Equivalent Clinical Outcomes Between Anatomical Alignment Versus Mechanical Alignment of Simultaneous Bilateral Total Knee Arthroplasty Using a Posterior-Stabilized Prosthesis During an Average Follow-Up of Five Years: A Prospective Randomized Clinical Trial.

BACKGROUND: This study aimed to investigate the differences in clinical outcomes between anatomical alignment and mechanical alignment in each knee, respectively, in patients who underwent bilateral total knee arthroplasty. METHODS: Bilateral simultaneous total knee arthroplasty using a posterior-stabilized prosthesis was performed between June 2016 and May 2018, with one knee undergoing anatomical alignment and the contralateral knee undergoing mechanical alignment, which was randomized. There were 80 knees in 40 patients (mean age 75 years, range 60 to 87, with 4 men and 36 women) followed up for at least two years (mean follow-up 4.9 years, range 2 to 7y). On the anatomical side, the distal femoral cut was set 2° more valgus to the mechanical axis, and the tibial cut was set to 2 or 3° varus using a specific guide. Implant position and lower extremity alignment were measured using postoperative radiographs and computed tomography images. The range of motion before and after surgery, Knee Society score, patient satisfaction, postoperative 2011 Knee Society questionnaire, and Knee Injury and Osteoarthritis Outcome Scores were evaluated. RESULTS: A significant difference was observed in joint line orientation (0.6 versus 2.9°, P < 0.001), but not in the postoperative hip-knee-ankle angle between two groups. There was one knee in the mechanical alignment group that required revision surgery at five years due to implant loosening. Before surgery, the anatomical alignment group had a significantly lower knee extension angle (-7.2 versus -6.0º, P = 0.035) and Knee Society score (46.1 versus 49.1, P = 0.046). No significant difference was observed between the groups except for the 2011 Knee Society questionnaire satisfaction scores (26.7 versus 25.7, P = 0.035). More participants preferred the anatomical alignment side postoperatively. CONCLUSION: Anatomical and mechanical alignments had similar clinical outcomes in patients undergoing bilateral total knee arthroplasty at a mean of 4.9 year follow-up.

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.

Lateral-medial asymmetry of posterior tibial slope and small lateral tibial plateau articular surface depth are morphological factors of lateral meniscus posterior root tears in ACL-injured patients.

PURPOSE: To investigate whether knee morphological features, patient characteristics, and intraoperative findings are associated with a lateral meniscus (LM) posterior root tear (LMPRT) in anterior cruciate ligament (ACL) injuries with the integrated data from two academic centres. METHODS: This retrospective study used registry data acquired prospectively at two academic centres. Patients with ACL reconstruction (ACLR) with LMPRT and no other LM injury were selected (LMPRT group) from each database. The control group included patients who underwent ACLR without LM tears. Patients were matched to the LMPRT group according to age and gender (1:1). Morphological factors evaluated on preoperative magnetic resonance image scans included lateral femoral condyle (LFC) anterior-posterior diameter, height, and depth; lateral tibial plateau (LTP) articular surface (AS) depth and sagittal plane depth; and lateral and medial posterior tibial slopes (PTSs). LFC height and depth ratios, LTP AS depth and sagittal plane depth ratios, and lateral-to-medial slope asymmetry were computed from previous measurements. Patient characteristics and intraoperative findings were extracted and compared between both groups. RESULTS: The study included 252 patients (126 in each group). The lateral-medial asymmetry of PTS was greater in the LMPRT group (1.2° vs 0.3°, p < 0.05), and the LTP AS depth was smaller in the LMPRT group (31.4 mm vs 33.2 mm, p < 0.01). There were no differences in LFC morphology between the control and LMPRT groups. Pivot shift grade (p < 0.05), percentage of complete ACL tears (p < 0.05), and medial meniscus ramp lesions (p < 0.05) were significantly higher in the LMPRT group. CONCLUSION: LMPRT was associated with significantly increased lateral-medial asymmetry of PTS and significantly smaller LTP AS depth. LMPRT was also associated with an increase in the preoperative pivot shift grade and the presence of a medial meniscus ramp lesion. These morphological characteristics are rather simple to measure and would serve as helpful indicators to preoperatively detect LMPRT, which is frequently challenging to diagnose preoperatively. LEVEL OF EVIDENCE: Level III.

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).

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).

Medial Tibial Osteophyte Width Strongly Reflects Medial Meniscus Extrusion Distance and Medial Joint Space Width Moderately Reflects Cartilage Thickness in Knee Radiographs.

BACKGROUND: The presence of medial tibial osteophytes on knee radiographs suggests cartilage wear, but may be associated with medial meniscus extrusion (MME). The joint space width of the medial compartment consists anatomically of cartilage and the medial meniscus, but which is most responsible for joint space narrowing remains unclear. Magnetic resonance imaging (MRI) reveals MME and cartilage thickness. PURPOSES: To determine which radiographic medial tibial osteophyte width correlates better with cartilage thickness or MME distance and which radiographic medial joint space width correlates better with cartilage thickness or MME distance. STUDY TYPE: Cross-sectional. POPULATION: Total of 527 subjects, 253 females and 274 males, aged 30-79 years, included in the Kanagawa Knee Study. FIELD STRENGTH/SEQUENCE: 3 T/fat-suppressed spoiled gradient echo and proton density weighted. ASSESSMENT: The medial tibial osteophyte width and "the minimum joint space width at the medial compartment" (mJSW) were measured from plain radiographs. The cartilage region was automatically extracted from MRI data using software. The medial femoral and tibial cartilage regions were each divided into nine subregions, and the average thickness of the cartilage was determined in each region and subregion. MME was manually measured by two orthopedic surgeons using MRI coronal section images. STATISTICAL TESTS: Pearson's correlation coefficient and their comparison, with P < 0.05 considered statistically significant. RESULTS: The absolute values of the correlation coefficients were 0.33 at maximum between osteophyte width and cartilage thickness and 0.76 between osteophyte width and MME; the value was significantly higher with MME than with cartilage thickness (P < 0.001). The absolute values of the correlation coefficients were 0.50 at maximum between mJSW and cartilage thickness and 0.16 between mJSW and MME; the value was significantly higher with cartilage thickness than with MME (P < 0.001). DATA CONCLUSION: The medial tibial osteophyte width strongly reflected MME and the medial joint space width moderately reflected cartilage thickness. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Difference in the joint space of the medial knee compartment between full extension and Rosenberg weight-bearing radiographs.

OBJECTIVES: Radiographs are the most widespread imaging tool for diagnosing osteoarthritis (OA) of the knee. Our purpose was to determine which of the two factors, medial meniscus extrusion (MME) or cartilage thickness, had a greater effect on the difference in the minimum joint space width (mJSW) at the medial compartment between the extension anteroposterior view (extension view) and the 45° flexion posteroanterior view (Rosenberg view). METHODS: The subjects were 546 participants (more than 50 females and 50 males in their 30 s, 40 s, 50 s, 60 s, and 70 s) in the Kanagawa Knee Study. The mJSW at the medial compartment was measured from both the extension and the Rosenberg views, and the "mJSW difference" was defined as the mJSW in the Rosenberg view subtracted from the mJSW in the extension view. The cartilage region was automatically extracted from MRI data and constructed in three dimensions. The medial region of the femorotibial joint cartilage was divided into 18 subregions, and the cartilage thickness in each subregion was determined. The MME was also measured from MRI data. RESULTS: The mJSW difference and cartilage thickness were significantly correlated at 4 subregions, with 0.248 as the highest absolute value of the correlation coefficient. The mJSW difference and MME were also significantly correlated, with a significantly higher correlation coefficient (0.547) than for the mJSW difference and cartilage thickness. CONCLUSIONS: The MME had a greater effect than cartilage thickness on the difference between the mJSW at the medial compartment in the extension view and in the Rosenberg view. KEY POINTS: • The difference in the width at the medial compartment of the knee between the extension and the flexion radiographic views was more affected by medial meniscus extrusion than by cartilage thickness.

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.

Effects of different surgical procedures for meniscus injury on two-year clinical and radiological outcomes after anterior cruciate ligament reconstructions. -TMDU MAKS study.

BACKGROUND: The treatment of meniscus injuries combined with anterior cruciate ligament (ACL) reconstruction would be important to improve outcomes after ACL reconstruction. However, the effects of treatment methods for meniscus after ACL reconstruction have not been thoroughly investigated. The objective of this study was to investigate the effects of treatment methods for meniscus on clinical and radiological outcomes at 2 years after ACL reconstruction. METHODS: Three-hundred and eighteen patients with primary ACL reconstruction using autologous hamstring tendon registered in our multicenter study database and who were followed up for 2 years were included. They were then divided into 3 groups, the no meniscal lesion/untreated group (n = 149), the meniscal repair group (n = 139), and the meniscal resection group (n = 30). Patient-based subjective evaluations (Lysholm score, Knee injury and Osteoarthritis Outcome score and International Knee Documentation Committee subjective score), objective evaluations (Lachman test, pivot shift test and KT measurement), and radiological measurements (medial and lateral joint space width) were compared among the 3 groups preoperatively and at 2 years follow-up. RESULTS: All subjective scores and objective evaluations significantly improved in all groups without significant differences among the groups postoperatively. Regarding radiological findings, the medial joint space width significantly decreased only in the resection group during the 2-year period, and the medial joint space width in the resection group was significantly smaller than that of the other groups at the 2-year follow-up. Moreover, the medial joint space width significantly decreased during the 2-year period when MM was resected. CONCLUSIONS: In radiological findings, medial meniscus resection decreased medial joint space width two years after ACL reconstruction. On the other hand, treatment methods for meniscus neither significantly affected subjective nor objective findings until the 2-year follow-up. LEVEL OF EVIDENCE: Ⅱ, Cohort study.

Knee laxity, lateral meniscus tear and distal femur morphology influence pivot shift test grade in ACL injury patients.

PURPOSE: Although several factors have been considered to be associated with pivot shift test grade in ACL injured patients, a conclusion regarding which factors contribute to the pivot shift test grade has not been reached. The purpose of this study was to identify factors associated with preoperative pivot shift test grade. METHODS: Three hundred and sixty-six consecutive patients who underwent ACL reconstruction in our hospital were enrolled in the study. Patients were divided into two groups on the basis of preoperative pivot shift test grade (Mild: grade 0-3, Severe: grade 4-6). First, 13 independent variables (age, gender, period from injury to surgery, hyperextension, KT measurement, contralateral side pivot shift test grade, medial and lateral tibial slope, lateral condyle length, lateral condyle height, distal femoral condyle offset, medial and lateral meniscus tear) were analyzed by one-way ANOVA and Chi-squared test. Binary Logistic regression was then performed based on the results of univariate analyses (independent variables of p < 0.2 were included). RESULTS: Hyperextension, lateral meniscus tear, contralateral side pivot shift test grade, distal femoral condyle offset and KT measurement were identified as risk factors for preoperative pivot shift grade via logistic regression analysis. CONCLUSION: The current study revealed that hyperextension, lateral meniscus tear, contralateral side pivot shift test grade, distal femoral condyle offset and anterior instability were associated with preoperative pivot shift grade. Patients with above factors that cannot be modified during surgery may need special consideration when ACL reconstruction is performed, as greater preoperative pivot shift has been proven to be a risk factor for residual pivot shift after ACL reconstruction. LEVEL OF EVIDENCE: III.

Trends in arthroplasty in Japan by a complete survey, 2014-2017.

BACKGROUND: Precise knowledge of the prevalence and trends of arthroplasty can facilitate the design of medical plans for efficient treatments. The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data Japan provides statistics about the annual number of arthroplasties (knee, hip, shoulder, finger, elbow, and foot/ankle) through health insurance claim numbers for these surgeries. The purpose of this study was to document the annual arthroplasty numbers between 2014 and 2017 in Japan and to analyze their four-year trends, gender differences, age distributions, and regional differences as revealed by the complete survey. METHODS: Numbers of arthroplasty surgeries were extracted from the NDB Open Data Japan for 2014-2017. For "knee", "hip", "shoulder", "finger", "elbow", and "foot/ankle" arthroplasties, we showed the annual arthroplasty numbers, annual arthroplasty numbers by age group, annual arthroplasty numbers in individual prefectures, and annual arthroplasty numbers per 100,000 population in individual prefectures. RESULTS: The annual arthroplasty numbers in 2017 were 146,189 for all joints, 82,304 for knees, 59,029 for hips, 2454 for shoulders, 1551 for fingers, 536 for elbows, and 291 for feet/ankles. For the four years up to 2017, the rate of alteration in the number of arthroplasties was +14% for total arthroplasties, +9% for knees, +21% for hip joints, +97% for shoulders, + 8% for fingers, -10% for elbows, and +25% for feet/ankles. The proportion of females was 70-90% and the peak age was between the late 60s and late 70s for all joints. Variations in arthroplasty numbers per population by prefecture appeared to be small for knees and hips and large for other joints. CONCLUSIONS: We revealed the annual total number of arthroplasties for each joint in Japan using the NDB Open Data Japan for the first time.

Effect of transplanted mesenchymal stem cell number on the prevention of cartilage degeneration and pain reduction in a posttraumatic osteoarthritis rat model.

BACKGROUND: Mesenchymal stem cells (MSCs) transplantation therapy is considered an alternative therapy to prevent posttraumatic osteoarthritis (PTOA). However, consensus as to the sufficient number of MSCs for the prevention of PTOA is lacking. The purpose of this study was to determine the sufficient number of MSCs to achieve PTOA prevention and the reduction in pain after anterior cruciate ligament transection (ACLT). METHODS: Eight-week-old male Wistar rats were used. ACLT was conducted in the knee joint as a PTOA model. According to the species-specific knee joint volume, 104 MSCs in rats are equivalent to 3 × 107 MSCs in humans, which was clinically prepared. MSCs (104, 105, or 106 cells) or phosphate-buffered saline were injected into the knee joint at 1, 2, and 3 weeks after ACLT. Histological examinations were performed at 12 weeks after ACLT. The weight-bearing distribution improvement ratio was calculated as an assessment of pain until 12 weeks after ACLT. RESULTS: Histological evaluations showed that all the MSCs groups except for 104 MSCs group in femur were significantly improved compared to the control group at 12 weeks after ACLT. The weight-bearing distribution in the 104 and 105 MSCs groups at 12 weeks after ACLT and in the 106 MSCs group at 6, 8, 10, and 12 weeks after ACLT were significantly higher than those of the control group. CONCLUSION: A clinically feasible number of MSCs was found to reduce the articular cartilage degeneration and to decrease pain in the PTOA model. Increasing numbers of the cells further protected the articular cartilage against degeneration.

Characteristics of MSCs in Synovial Fluid and Mode of Action of Intra-Articular Injections of Synovial MSCs in Knee Osteoarthritis.

We have been studying mesenchymal stem cells (MSCs) in synovial fluid and the intra-articular injection of synovial MSCs in osteoarthritis (OA) knees. Here, mainly based on our own findings, we overview the characteristics of endogenous MSCs in the synovial fluid of OA knees and their mode of action when injected exogenously into OA knees. Many MSCs similar to synovial MSCs were detected in the synovial fluid of human OA knees, and their number correlated with the radiological OA grade. Our suspended synovium culture model demonstrated the release of MSCs from the synovium through a medium into a non-contacting culture dish. In OA knees, endogenous MSCs possibly mobilize in a similar manner from the synovium through the synovial fluid and act protectively. However, the number of mobilized MSCs is limited; therefore, OA progresses in its natural course. Synovial MSC injections inhibited the progression of cartilage degeneration in a rat OA model. Injected synovial MSCs migrated into the synovium, maintained their MSC properties, and increased the gene expressions of TSG-6, PRG-4, and BMP-2. Exogenous synovial MSCs can promote anti-inflammation, lubrication, and cartilage matrix synthesis in OA knees. Based on our findings, we have initiated a human clinical study of synovial MSC injections in OA knees.

Morphological changes in synovial mesenchymal stem cells during their adhesion to the meniscus.

Synovial mesenchymal stem cells (MSCs) are an attractive cell source for transplantation because of their high chondrogenic potential, especially in areas like the meniscus of the knee. A synovial MSC suspension placed onto the meniscus for 10 min promoted healing of repaired meniscal tears that generally do not heal. Here, we quantified the proportion of human synovial MSCs that adhered to a porcine abraded meniscus, clarified their morphological changes, and revealed the mechanism by which the synovial MSCs adhered to the meniscus. The numbers of adhering cells at immediately after 10, 60 min and 6, 24 h after suspension placement were calculated. The meniscus surface was examined by scanning electron microscopy, and 50 cells were randomly selected at each time period, classified, and quantified for each of the six donors. Approximately 28% of the synovial MSCs immediately adhered to the meniscus after placement and the proportion of adhered cells increased further with time. All cells maintained a round shape for 60 min, and then transformed to a mixture of round and semi-flattened cells. By 24 h, flattened cells covered the meniscus. Microspikes were observed in 36% of the floating synovial MSCs and in 76% of the cells on the meniscus shortly after placement on the meniscus, then the proportion of cells with pseudopodia increased. The bleb-dominant cell proportion significantly decreased, and the smooth-dominant cell proportion increased within 60 min. Microspikes or the bodies of synovial MSCs were trapped by meniscal fibers immediately after placement. The proportion of adhered cells increased with time, and the cell morphology changed dynamically for 24 h as the synovial MSCs adhered to the meniscus. The MSCs in the round morphological state had a heterogeneous morphology. The microspikes, and the subsequent development of pseudopodia, may play an important role in adhesion onto the meniscus.

Synovial fluid-derived mesenchymal cells have non-inferior chondrogenic potential and can be utilized for regenerative therapy as substitute for synovium-derived cells.

Recent progress in the field of mesenchymal stem cell (MSC) biology has enabled their clinical application. In the autologous cell transplantation therapy, the source of MSCs are quite important to reduce patients' physical burden. In this study, we isolated MSCs from the synovial fluid (SF) and synovial membrane (Syn) of the same patients and compared the biological characteristics of them. In vitro and in vivo experiments indicated the non-inferior chondrocytic differentiation and articular cartilage regeneration potential of SF-MSCs compared to that of Syn-MSCs; however, SF-MSCs showed less proliferative potential than Syn-MSCs in vitro. Flow cytometry-based multiplex surface antigen expression analyses indicated that SF-MSCs exhibit fewer cells positive for CD140, which is a functional growth factor receptor for MSCs. Nevertheless, we obtained enough SF-MSCs for transplantation within several passages. Since arthrocentesis is routinely performed during outpatient care in the consultation room and is less invasive than synovial biopsy, MSC derived from synovial fluid could be considered an attractive cell source for cartilage regenerative therapy as a substitute for Syn-MSC. Developing these cells for clinical application may greatly benefit patients undergoing autologous MSC transplantation therapy.

The effect of a centralization procedure for extruded lateral meniscus on load distribution in porcine knee joints at different flexion angles.

BACKGROUND: Meniscal extrusion results in loss of the ability to resist hoop strain and biomechanical overload on the joint articular surface. A centralization technique has been developed to overcome these problems. In this study, we analyzed the biomechanics of the extruded and centralized lateral meniscus (LM) in porcine knee joints at different flexion angles. METHODS: Porcine knee joints (n = 8) were set in the universal tester and each knee was tested under the following states: 1) intact; 2) extrusion-meniscal extrusion was created by resecting the posterior root of the LM and posterior synovial capsule; and 3) centralization-centralization was performed by two anchors inserted in the lateral tibial plateau. Deviation distance of the meniscus, contact pressure, and contact area in the anterior LM, middle LM, posterior LM, and the contact pressure of the tibial cartilage were evaluated with an axial compressive force of 200 N at knee flexion angles of 30°, 45°, 60°, and 90°. RESULTS: The deviation distance of LM significantly increased in extrusion but was restored to the intact status after centralization at all angles. Both the contact pressure and area significantly decreased in extrusion and were restored after centralization close to the intact status in the anterior and middle LM; in the posterior LM, however, decreased contact pressure and area were not restored after centralization. The contact pressure of the tibial cartilage increased significantly in extrusion but decreased close to the intact status after centralization. CONCLUSIONS: This centralization procedure could reduce extrusion of the LM and restore the load-distributing function of the anterior-middle LM. However, the procedure itself could not restore hoop function in cases where the defect lies in the posterior LM.

Relationship between medial meniscus extrusion and cartilage measurements in the knee by fully automatic three-dimensional MRI analysis.

BACKGROUND: We developed a fully automatic three-dimensional knee MRI analysis software that can quantify meniscus extrusion and cartilage measurements, including the projected cartilage area ratio (PCAR), which represents the ratio of the subject's actual cartilage area to their ideal cartilage area. We also collected 3D MRI knee data from 561 volunteers (aged 30-79 years) from the "Kanagawa Knee Study." Our purposes were to verify the accuracy of the software for automatic cartilage and meniscus segmentation using knee MRI and to examine the relationship between medial meniscus extrusion measurements and cartilage measurements from Kanagawa Knee Study data. METHODS: We constructed a neural network for the software by randomly choosing 10 healthy volunteers and 103 patients with knee pain. We validated the algorithm by randomly selecting 108 of these 113 subjects for training, and determined Dice similarity coefficients from five other subjects. We constructed a neural network using all data (113 subjects) for training. Cartilage thickness, cartilage volume, and PCAR in the medial femoral, lateral femoral, medial tibial, and lateral tibial regions were quantified by using the trained software on Kanagawa Knee Study data and their relationship with subject height was investigated. We also quantified the medial meniscus coverage ratio (MMCR), defined as the ratio of the overlapping area between the medial meniscus area and the medial tibial cartilage area to the medial tibial cartilage area. Finally, we examined the relationship between MMCR and PCAR at middle central medial tibial (mcMT) subregion located in the center of nine subregions in the medial tibial cartilage. RESULTS: Dice similarity coefficients for cartilage and meniscus were both approximately 0.9. The femoral and tibial cartilage thickness and volume at each region correlated with height, but PCAR did not correlate with height in most settings. PCAR at the mcMT was significantly correlated with MMCR. CONCLUSIONS: Our software showed high segmentation accuracy for the knee cartilage and meniscus. PCAR was more useful than cartilage thickness or volume since it was less affected by height. Relations ips were observed between the medial tibial cartilage measurements and the medial meniscus extrusion measurements in our cross-sectional study. TRIAL REGISTRATION: UMIN, UMIN000032826 ; 1 September 2018.

Editorial Commentary: Mesenchymal Stem Cell Preparation Methods Affect the Properties of Shoulder Subacromial Bursa-Derived Cells.

Augmentation of mesenchymal stem cells (MSCs) from the subacromial bursa in the setting of irreparable rotator cuff tears is a powerful candidate for future regenerative medicine. However, little is known about whether the preparation technique affects the individual differences and potentials of subacromial bursa-derived MSCs. The yields obtained by chopping or cell-expansion techniques with a high-density of initial nucleated cells seem to be lower than those obtained with low-density cell-expansion techniques. Differences in cell-preparation methods may affect whether individual differences in their properties exist. Further studies are required using a low-density cell-expansion technique to establish a new regenerative treatment using subacromial bursa-derived MSCs for irreparable rotator cuff tears.

Editorial Commentary: Are We Ready to Apply Stem Cell Therapy in Rotator Cuff Tear Surgery?

For rotator cuff tear surgery, application of mesenchymal stem cells (MSCs) is a promising new option. Among various MSC sources, synovial tissue contains a high number of MSCs with high chondrogenic potential. Because chondrogenic formation is an important factor in enthesis healing in rotator cuff repair, synovial MSCs derived from the subacromial bursa are superior candidates for the augmentation of rotator cuff tear surgery.