Synovium-derived Cells Research Articles

Pulsed Electromagnetic Field Therapy and Direct Current Electric Field Modulation Promote the Migration of Fibroblast-like Synoviocytes to Accelerate Cartilage Repair In Vitro.

Articular cartilage injuries are a common source of joint pain and dysfunction. As articular cartilage is avascular, it exhibits a poor intrinsic healing capacity for self-repair. Clinically, osteochondral grafts are used to surgically restore the articular surface following injury. A significant challenge remains with the repair properties at the graft-host tissue interface as proper integration is critical toward restoring normal load distribution across the joint. A key to addressing poor tissue integration may involve optimizing mobilization of fibroblast-like synoviocytes (FLS) that exhibit chondrogenic potential and are derived from the adjacent synovium, the specialized connective tissue membrane that envelops the diarthrodial joint. Synovium-derived cells have been directly implicated in the native repair response of articular cartilage. Electrotherapeutics hold potential as low-cost, low-risk, non-invasive adjunctive therapies for promoting cartilage healing via cell-mediated repair. Pulsed electromagnetic fields (PEMFs) and applied direct current (DC) electric fields (EFs) via galvanotaxis are two potential therapeutic strategies to promote cartilage repair by stimulating the migration of FLS within a wound or defect site. PEMF chambers were calibrated to recapitulate clinical standards (1.5 ± 0.2 mT, 75 Hz, 1.3 ms duration). PEMF stimulation promoted bovine FLS migration using a 2D in vitro scratch assay to assess the rate of wound closure following cruciform injury. Galvanotaxis DC EF stimulation assisted FLS migration within a collagen hydrogel matrix in order to promote cartilage repair. A novel tissue-scale bioreactor capable of applying DC EFs in sterile culture conditions to 3D constructs was designed in order to track the increased recruitment of synovial repair cells via galvanotaxis from intact bovine synovium explants to the site of a cartilage wound injury. PEMF stimulation further modulated FLS migration into the bovine cartilage defect region. Biochemical composition, histological analysis, and gene expression revealed elevated GAG and collagen levels following PEMF treatment, indicative of its pro-anabolic effect. Together, PEMF and galvanotaxis DC EF modulation are electrotherapeutic strategies with complementary repair properties. Both procedures may enable direct migration or selective homing of target cells to defect sites, thus augmenting natural repair processes for improving cartilage repair and healing.

TAMRA-conjugated DRL tripeptide for the visualization of synovium

The development of new cell-/organ-targeting peptides has been highlighted across various basic research fields and industries. In this work, a new synovium-homing tri-peptide, DRL, was developed through peptide screening and was functionalized to visualize the synovium via 5-carboxytetramethylrhodamine (TAMRA; TAM) conjugation. The TAMRA-conjugated DRL, named DRL-TAM, showed a bright red emission in cells and tissues with high biocompatibility (low cytotoxicity and biotoxicity). In the cell screening and in vivo fluorescence imaging studies, DRL-TAM demonstrated a remarkable visualization ability on the synovial-derived cells and synovial-related organs. DRL-TAM, as an advanced next generation of synovium-homing peptide, could open up new possibilities for the synovium-related disease diagnosis and treatment.

Low-dose irradiation could mitigate osteoarthritis progression via anti-inflammatory action that modulates mitochondrial function

PurposeThe use of low-dose radiation therapy (LDRT) for osteoarthritis (OA) are rarely implemented, except in some European regions. Its clinical effects are controversial but little is known about how LDRT affects actual disease progression. We conducted a preclinical study to reveal the potential underlying mechanisms related to its disease modifying abilities. Methods and MaterialsUsing primary cultured human chondrocytes and synovium-derived cells obtained from OA patients, the effects of LDRT were measured by quantitative real-time PCR, western blotting, and mRNA sequencing. For in vivo validation, a surgically-induced isolated OA model was used after anterior cruciate ligament transection or surgical destabilization of the medial meniscus. ResultsLDRT decreased the expression of pro-inflammatory factor matrix metalloproteinase 13 (MMP13) in chondrocytes. By contrast, collagen type 2 (COL2) protein expression was increased. LDRT induced large transcriptomic changes in both chondrocytes/synoviocytes, especially in mitochondrial activities. Gene set variation analysis demonstrated inverted U-shaped response in several categories, such as mitochondrial unfolded protein responses and extracellular matrix interactions. Growth differentiation factor 15 (GDF15), which is a mitohormetic signaling factor, was increased after LDRT and mediated the anti-inflammatory effects. Aggrecan was increased in synoviocyte’s medium and TNF-α was decreased in chondrocyte’s medium after LDRT. Conversely, knockdown of GDF15 did not result in decreased MMP13 expression by LDRT. Next, OA rats treated with LDRT exhibited a decreased OA severity when compared with the no-irradiation group at 10 weeks post-surgery (mean OARSI score 3.7 in 0 Gy, 2.8 in 0.5 Gy, and 1.8 in 1 Gy; p = 0.003). Osteoclast activity was significantly reduced in the LDRT group. ConclusionsTaken together, these data show that LDRT could mitigate osteoarthritis progression by exerting its anti-inflammatory effects via mitochondrial function modulation.

Interplay Between Iron Overload and Osteoarthritis: Clinical Significance and Cellular Mechanisms.

There are multiple diseases or conditions such as hereditary hemochromatosis, hemophilia, thalassemia, sickle cell disease, aging, and estrogen deficiency that can cause iron overload in the human body. These diseases or conditions are frequently associated with osteoarthritic phenotypes, such as progressive cartilage degradation, alterations in the microarchitecture and biomechanics of the subchondral bone, persistent joint inflammation, proliferative synovitis, and synovial pannus. Growing evidences suggest that the conditions of pathological iron overload are associated with these osteoarthritic phenotypes. Osteoarthritis (OA) is an important complication in patients suffering from iron overload-related diseases and conditions. This review aims to summarize the findings and observations made in the field of iron overload-related OA while conducting clinical and basic research works. OA is a whole-joint disease that affects the articular cartilage lining surfaces of bones, subchondral bones, and synovial tissues in the joint cavity. Chondrocytes, osteoclasts, osteoblasts, and synovial-derived cells are involved in the disease. In this review, we will elucidate the cellular and molecular mechanisms associated with iron overload and the negative influence that iron overload has on joint homeostasis. The promising value of interrupting the pathologic effects of iron overload is also well discussed for the development of improved therapeutics that can be used in the field of OA.

Injectable Therapeutic Organoids Using Sacrificial Hydrogels

SummaryOrganoids are becoming widespread in drug-screening technologies but have been used sparingly for cell therapy as current approaches for producing self-organized cell clusters lack scalability or reproducibility in size and cellular organization. We introduce a method of using hydrogels as sacrificial scaffolds, which allow cells to form self-organized clusters followed by gentle release, resulting in highly reproducible multicellular structures on a large scale. We demonstrated this strategy for endothelial cells and mesenchymal stem cells to self-organize into blood-vessel units, which were injected into mice, and rapidly formed perfusing vasculature. Moreover, in a mouse model of peripheral artery disease, intramuscular injections of blood-vessel units resulted in rapid restoration of vascular perfusion within seven days. As cell therapy transforms into a new class of therapeutic modality, this simple method—by making use of the dynamic nature of hydrogels—could offer high yields of self-organized multicellular aggregates with reproducible sizes and cellular architectures.

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.

メカニカルストレスに対するヒト滑膜由来幹細胞を用いた三次元培養組織の長期的応答(大阪歯科大学大学院歯学研究科博士(歯学)学位論文内容要旨および論文審査結果要旨の公表)

メカニカルストレスに対するヒト滑膜由来幹細胞を用いた三次元培養組織の長期的応答(大阪歯科大学大学院歯学研究科博士(歯学)学位論文内容要旨および論文審査結果要旨の公表)

From osteoarthritic synovium to synovial-derived cells characterization: synovial macrophages are key effector cells.

BackgroundThe aim of the study was to characterize synovial cells from OA synovium with low-grade and moderate-grade synovitis and to define the role of synovial macrophages in cell culture.MethodsSynovial tissue explants were analyzed for the expression of typical markers of synovial fibroblasts (SF), synovial macrophages (SM) and endothelial cells. Synovial cells at passage 1 (p.1) and 5 (p.5) were analyzed for different phenotypical markers by flow cytometric analysis, inflammatory factors by multiplex immunoassay, anabolic and degradative factors by qRT-PCR. P.1 and p.5 synovial cells as different cell models were co-cultured with adipose stem cells (ASC) to define SM effects.ResultsSynovial tissue showed a higher percentage of CD68 marker in moderate compared with low-grade synovitis. Isolated synovial cells at p.1 were positive to typical markers of SM (CD14, CD16, CD68, CD80 and CD163) and SF (CD55, CD73, CD90, CD105, CD106), whereas p.5 synovial cells were positive only to SF markers and showed a higher percentage of CD55 and CD106. At p.1 synovial cells released a significantly higher amount of all inflammatory (IL6, CXCL8, CCL2, CCL3, CCL5) and some anabolic (IL10) factors than those of p.5. Moreover, p.1 synovial cells also expressed a higher amount of some degradative factors (MMP13, S100A8, S100A9) than p.5 synovial cells. Co-culture experiments showed that the amount of SM in p.1 synovial cells differently induced or down-modulated some of the inflammatory (IL6, CXCL8, CCL2, CCL3, CCL5) and degradative factors (ADAMTS5, MMP13, S100A8, S100A9).ConclusionsWe found that p.1 (mix of SM and SF) and p.5 (only SF) synovial cells represent two cell models that effectively reproduce the low- or moderate-grade synovitis environment. The presence of SM in culture specifically induces the modulation of the different factors analyzed, confirming that SM are key effector cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0983-4) contains supplementary material, which is available to authorized users.

Characterization of synovial-derived cells from ostheoarthritic synovium: evidence that macrophages are key effector cells

Characterization of synovial-derived cells from ostheoarthritic synovium: evidence that macrophages are key effector cells

Adipose stromal cells effects on osteoarthritic synoviocytes are dependent by macrophages

Adipose stromal cells effects on osteoarthritic synoviocytes are dependent by macrophages

Effect of Cryopreservation and Cell Passage Number on Cell Preparations Destined for Autologous Chondrocyte Transplantation

Autologous chondrocyte transplantation (ACT) is an effective and safe therapy for repairing articular cartilage defects and requires cell preservation and subculture before transplantation. We compared the effects of cryopreservation and passaging on cell viability, proliferation, and maintenance of the function of chondrocytes and synovium-derived mesenchymal stem cells (MSCs) used as sources for ACT. These cells were isolated from the knee joints of rabbits and were cultured, passaged serially, and divided into 2 groups that were either cryopreserved or not. The morphology, viability, gene expression, and differentiation potential of the 2 groups were compared. Maintenance of the potential to undergo chondrogenic differentiation was determined with the use of a 3-dimensional culture method. Passaging and cryopreservation significantly affected the ability of chondrocytes to maintain their morphology, express chondrogenic genes, and differentiate. In contrast, synovium-derived cells were not affected by passaging and cryopreservation. Our results may serve as the foundation for the application of passaged and cryopreserved chondrocyte or other source cells of MSCs in ACT.

Celecoxib down-regulates mechanically induced ADAMTS-4 gene expression in 3D cultured tissue of human synovium-derived cells at lower concentration than indomethacin

Temporomandibular disorder (TMD) is a disease or disorder of the temporomandibular joint and maticatory muscles that is sometimes caused by anterior displacement of the articular discs. When clenching the teeth, compressive force is applied directly to the synovium in the disc, which is displaced anteriorly, causing synovitis. Increased levels of inflammatory modulators, such as cytokines, nitric oxide, and cartilage matrix catabolites, as well as matrix metalloproteinases (MMPs), are found in the synovial fluid with TMD. MMPs derived from fibrocartilage and cartilage cells are considered key enzymes that are responsible for extracellular matrix (ECM) breakdown in the TMJ. Further, in recent years, not only MMPs, but also a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) have been attracting attention as proteinases that degrade the ECM of cartilage. Among them, especially ADAMTS-4 and ADAMTS-5 are known to degrade aggrecan in the extracellular matrix. 7 Until now, an arthritis model was produced by stimulation of IL-1β, tension stress, and hydrostatic fluid pressure. We have developed a novel arthritis model using a cyclic loading bioreactor (CLS-7J ; Technoview, Osaka, Japan), and cultured human synovial cells in a three-dimensional (3D) cell-scaffold Celecoxib down-regulates mechanically induced ADAMTS-4 gene expression in 3D cultured tissue of human synovium-derived cells at lower concentration than indomethacin

Preparation and Characterization of a Novel Injectable Hydrogel

Injectable hydrogels have emerged as a great candidate in tissue engineering for they can be delivered via a minimally invasive manner. Here, we report an in situ forming hydrogel composited of oxidized dextran (Odex) and modified gelatin. The dynamic gelling process was measured through rheological measurements. The effect of the ratio of Odex and gelatin on gelling time, microstructure, swelling ratio and in vitro degradation of the composite hydrogels were examined. Biological assess was performed through WST-1 Assay by using Synovium-derived Mesenchymal Cells (SMSCs). According to the results, adjustable physicochemical properties can be obtained through simply altering the ratio of Odex and gelatin. Moreover, with the increase of incorporated gelatin, better biocompatibility was shown in the composite hydrogels, which exhibited its potentially high application prospect in the field of cartilage tissue engineering.

Chondrogenic potentials of human synovium-derived cells sorted by specific surface markers

We aimed to evaluate expression levels of nine candidate surface markers for chondrogenic potential in human synovial cells and to determine whether cell pellets positively sorted by each specific marker would have valuable chondrogenic potential. The expression levels of the selected nine leading surface markers in synovial cells from knee joints in 15 patients with primary knee osteoarthritis were evaluated at the stage of isolation and after cultivation using flow cytometry. We obtained positive and negative cells for each surface marker using a magnetically activated cell sorting method and compared chondrogenic potentials between the positive and the negative cell pellets. CD29, CD44, CD73, and CD90 were expressed on the most synovial cells at the isolation stage and on almost all cells at stage of P0 and P1. CD133 was rarely expressed at any stages of the evaluated cells. CD166 was expressed in 7.1% of cells at the isolation stage on average, but this expression increased after cell passages. The expressions of CD10 and CD105 also increased after cell passages while the expression of CD49a made no significant difference at progressive stages of isolation and passage. Comparison of chondrogenic potentials between positive and negative cell pellets for each marker revealed that only CD105- and CD166-positive cell pellets showed better chondrogenic potentials (type II collagen gene expression, cartilage matrix formation, and GAG expression) than the corresponding negative cell pellets. Our study suggests that CD105 and CD166 would be valuable surface markers associated with chondrogenic potential; thus, CD105- and CD166-enriched cells derived from human synovium would be practical and valuable sources for cartilage regeneration.

Tissue Engineering Construct Prevents Disk Degeneration after Nucleotomy in a Rat Model

Introduction Back pain, a significant source of morbidity in our society, is directly linked to the pathology of the intervertebral disk (IVD). An IVD is a complex structure that is separated into the following three tissue types: the annulus fibrosus, the nucleus pulposus (NP), and the endplates. Recently, IVD engineering strategies have been increasingly focused on the regeneration or repair of the AF to increase the potential of NP engineering strategies and to mechanically assist NP replacement therapies.1,2 We have developed a novel scaffold-free three-dimensional tissue-engineered construct (TEC) derived from cultured synovial mesenchymal stem cells (MSCs) as a unique approach for cartilage repair.3,4 Previous in vitro studies reveal that growth factors and serum can modify the collagen expression and glycosaminoglycan (GAG) content of chondrogenic-differentiated MSCs.5 Therefore although there is a difference between hyaline cartilage and fibrocartilage, TEC derived from MSCs could have a potential to differentiate into the AF, a fibrocartilage in IVD. This study explores the use of TEC derived from synovial MSCs as a cell-based therapy for IVD regeneration. Materials and Methods Synovial MSCs were isolated enzymatically from rat synovial membranes as previously reported.3,4 For development of the TEC, cells were cultured at the density of 4.0 × 105/cm2 in HG-DMEM in the presence of 0.2 mM ascorbic acid 2-phosphate for 2 weeks. The monolayer cultured cell-matrix complex was then detached from cell-substratum interface by addition of shear stress to convert to suspension culture. The cell-matrix complex immediately starts active contraction to form the three dimensional (3D) tissue-engineered construct (TEC, Fig. 1). To explore the use of TEC in degenerative spine, rat caudal IVD were denucleated and treated with TEC (controls were denucleation only). Nine male Sprague-Dawley rats (300 to 400 g) were used, and two most cranial tail disks were denucleated in each rat, giving three disks per group per time point. At 2, 8, and 12 weeks after implantation, the animals were euthanized and disks were evaluated for disk height based on micro-CT analysis, histology including Safranin O staining, and disk grade based on a scoring system.6 Results At the 2-week time point, there were no significant differences in disk height and disk grade between two groups (3.57 ± 0.28 vs 3.76 ± 0.46 points, p > 0.05) (462 ± 39 vs. 602 ± 49 um, p > 0.05). At the 8-week time point, the TEC-treated group showed significantly better results in disk grade (5 ± 0 vs. 3.14 ± 0.28 points, P<0.05). At the 12-week time point, TEC-treated group showed the higher disk height (234 ± 19 vs 584 ± 45 um, P<0.05) and better disk grade (5 ± 0 vs. 2.86 ± 0.46 points, p < 0.05). Untreated group experienced severe disruption of the AF and end plate, whereas such degenerative changes were alleviated with TEC implantation (Fig. 2). Conclusion This study shows that TEC may prevent postnucleotomy disk degeneration in vivo. Larger animals and longer time points will be necessary to further judge potential clinical impact. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared Andersson GB, et al. Directions for future research. Journal of Joint and Bone Surgery 2006 Wilke HJ, et al. Is a collagen scaffold for a tissue engineered nucleus replacement capable of restoring disc height and stability in an animal model? European Spine Journal 2006 W Ando, et al. Cartilage repair using an in vitro generated scaffold-free tissue-engineered construct derived from porcine synovial mesenchymal stem cells. Biomaterials 2007 K Shimomura, et al. The influence of skeletal maturity on allogenic synovial mesenchymal stem cell-based repair of cartilage in a large animal model. Biomaterials 2010 S Lee, et al. Effect of serum and growth factors on chondrogenic differentiation of synovium-derived stromal cells. Tissue Engineering: Part A 2009 AA Allon, et al. Structured coculture of stem cells and disc cells prevent disc degeneration in a rat model. The Spine Journal 2010

7F33 滑膜由来細胞と軟骨細胞の組織形成に与える圧縮負荷培養の影響(OS20 組織再生とバイオマテリアル)

7F33 滑膜由来細胞と軟骨細胞の組織形成に与える圧縮負荷培養の影響(OS20 組織再生とバイオマテリアル)

Transplantation of scaffold-free spheroids composed of synovium-derived cells and chondrocytes for the treatment of cartilage defects of the knee

Autologous chondrocyte implantation (ACI) is the treatment of choice for osteoarthritis. However, to regenerate articular cartilage using this method, the procedure paradoxically demands that the cell source of the articular chondrocytes (ACs) for ex vivo expansion be from the patient's own healthy cartilage, which can result in donor site morbidity. Accordingly, it is essential to develop a substitute for AC. In the present study, we investigated whether synovium-derived cells (SYs) could be used as a partial replacement for ACs in ACI. ACs and SYs from the knees of rabbits were isolated and cultured, and the growth rates of the cells were compared. To manufacture the cellular transplants, we developed a high-density suspension-shaking culture method (HDSS), which circulates the cells in culture media, promoting self-assembly of scaffold-free cellular aggregates. ACs and SYs were mixed in various ratios using HDSS. Injectable cellular transplants were harvested and transplanted into full-thickness osteochondral defects. Simultaneously, histological evaluations were conducted with toluidine blue and safranin O, and immunohistochemistry of collagen type I and II was conducted. Gene expression to evaluate chondrocyte-specific differentiation was also performed. We successfully prepared a large quantity of spheroids (spheroidal cell aggregates) in a short time using mixed ACs and SYs, for all cellular composition ratios. Our data showed that the minimal therapeutic unit for the transplants contributed to in situ regeneration of cartilage. In summary, SYs can be used as a replacement for ACs in clinical cases of ACI in patients with broad areas of osteoarthritic lesions.

Paper # 158: Co-implantation with Minced Articular Cartilage Enhances Chondrogenic Differentiation of Synovial Cells

IntroductionAutologous chondrocyte implantation (ACI) requires two-step surgical procedure, first to isolate the chondrocytes, and then to implant the in vitro cultured cells. Because of cost, time, and the special culture facilities needed, ACI has limited clinical application. Furthermore, the chondrocytes used for implantation are harvested from normal cartilage of the same joint, limiting the number of available cells.Recently, a direct implantation of minced cartilage in articular cartilage defects was attempted to omit the in vitro cell culture step [1Lu Y. et al.J Orthop Res. 2006; Google Scholar]. Although it was possible to improve implantation from a two-step to one-step procedure, the problem with ACI of having a limited number of cells for implantation remains unresolved. Thus, recent attempts have been made to use chondroprogenitor cells like synovium-derived cells, which were considered to be useful for cartilage implants [2Sakaguchi Y. et al.Arthritis Rheum. 2005; PubMed Google Scholar, 3Shintani N. et al.Arthritis Rheum. 2007; PubMed Google Scholar].We hypothesized that combined implantation of minced cartilage and enzymatically isolated primary synovial cells might be useful as a novel, one-step repair approach to solve the problems associated with ACI. Therefore, in the present study, we investigated the effects of co-implantation of minced cartilage with uncultured primary synovial cells on the chondrogenic differentiation of the synovial cells.

Local Administration of Autologous Synovium-Derived Cells Improve the Structural Properties of Anterior Cruciate Ligament Autograft Reconstruction in Sheep

Background: The structural properties of a tendon autograft deteriorate during the remodeling phase after anterior cruciate ligament (ACL) reconstruction. Hypothesis: A local application of autologous synovium-derived cells cultured in medium supplemented with transforming growth factor β (TGFβ) may inhibit the deterioration of structural properties of the tendon graft after ACL reconstruction. Study Design: Controlled laboratory study. Methods: Fifty-two mature sheep were used. In each animal, the right knee underwent ACL reconstruction using the semitendinosus tendon autograft; then, the animals were divided into 5 groups of 10. No additional treatments were applied in group 1, whereas fibrin sealant was applied around the graft in group 2. In group 3, autologous synovium-derived cells cultured in standard medium were applied around the graft with fibrin sealant, whereas autologous synovium-derived cells cultured in TGFβ-supplemented medium were applied with fibrin sealant in group 4. In group 5, fibrin sealant containing 20 ng of TGFβ was applied around the graft. Each animal was sacrificed at 12 weeks after the surgery. In each group, 7 and 3 sheep were used for biomechanical and histologic evaluations, respectively. The remaining 2 sheep were used to confirm whether the applied cells infiltrated the graft at 1 week after surgery. Results: Confocal microscope observations showed that the applied cells that were labeled before implantation infiltrated into the superficial portion of the graft at 1 week. Biomechanically, the maximum load and the stiffness of groups 4 and 5 were significantly greater than those of groups 1, 2, and 3. Histologically, necrotic lesions were observed in the core portion of the midsubstance in groups 1 and 2. In groups 3, 4, and 5, no necrotic lesions were found in the midsubstance. Conclusion: A local application of autologous synovium-derived cells cultured in TGFβ-supplemented medium or a fibrin sealant containing TGFβ significantly inhibits the natural deterioration of the structural properties of the tendon graft after ACL reconstruction. Clinical Relevance: Administration of autologous synovium-derived cells cultured in TGFβ-supplemented medium or TGFβ and fibrin glue alone can be a potential cell-based therapy to prevent graft deterioration after transplantation or accelerate mechanical restoration of the deteriorated graft.

Articular cartilage repair using an intra‐articular magnet and synovium‐derived cells

The purpose of this study was to investigate the chondrogenic potential of magnetically labeled synovium-derived cells (M-SDCs) and examine whether M-SDCs could repair the articular cartilage using an intra-articular magnet after delivery to the lesion. Synovium-derived cells (SDCs) were cultured from the synovium of a rat knee, and were magnetically labeled with ferumoxides. M-SDCs were examined with a transmission electron microscope. A pellet culture system was used to evaluate the chondrogenic potential of M-SDCs in a magnetic field. In a rat model, allogeneic M-SDCs were injected into the knee after we made an osteochondral defect on the patellar groove and implanted an intra-articular magnet at the bottom of the defect. We histologically examined the defects at 48 h, 4 weeks, 8 weeks, and 12 weeks after treatment. Electron microscopy showed the transfection of ferumoxides into SDCs. The pellet cultures revealed the chondrogenic potential of M-SDCs in a magnetic field. M-SDCs accumulated in the osteochondral defect at 48 h after treatment, and we confirmed the regeneration of the articular cartilage at 4 weeks, 8 weeks, and 12 weeks after treatment using an intra-articular magnet. We demonstrated that articular cartilage defects could be repaired using an intra-articular magnet and M-SDCs. We believe that this system will be useful to repair human articular cartilage defects.