Corneal Repair with Adhesive Cell Sheets of Fetal Cartilage-Derived Stem Cells

BACKGROUND@#Corneal scarring or disease may lead to severe corneal opacification and consequently, severe loss of vision due to the complete loss of corneal epithelial cells. We studied the use of epithelial cell sheets differentiated from fetal cartilage-derived stem cells (FCSC) to resurface damaged cornea. @*METHODS@#The FCSC were isolated from the femoral head of immature cartilage tissue. The ability of the FCSCs to differentiate into corneal epithelial cells was evaluated using differentiation media at 2 days and 7 days post-seeding. A sheet fabricated of FCSCs was also used for the differentiation assay. The results of the in vitro studies were evaluated by immunocytochemistry and Western blots for corneal epithelial cell markers (CK3/12 and Pax6) and limbal epithelial stem cell markers (ABCG2 and p63). To test the material in vivo, an FCSC-sheet was applied as a treatment in a chemically burned rabbit model. The healing ability was observed histologically one week after treatment. @*RESULTS@#The in vitro experiments showed morphological changes in the FCSCs at two and seven days of culture. The differentiated cells from the FCSCs or the FCSC-sheet expressed corneal epithelial cells markers. FCSC were create cell sheet that successfully differentiated into corneal epithelial cells and had sufficient adhesion so that it could be fused to host tissue after suture to the ocular surface with silk suture. The implanted cell sheet maintained its transparency and the cells were alive a week after implantation. @*CONCLUSION@#These results suggest that carrier-free sheets fabricated of FCSCs have the potential to repair damaged corneal surfaces.

Exosomes from IL-1b-Primed Mesenchymal Stem Cells Inhibited IL-1b- and TNF-a-Mediated Inflammatory Responses in Osteoarthritic SW982 Cells

BACKGROUND@#Exosomes from mesenchymal stem cells (MSCs) show anti-inflammatory effect on osteoarthritis (OA); however, their biological effect and mechanism are not yet clearly understood. This study investigated the anti-inflammatory effect and mechanism of MSC-derived exosomes (MSC-Exo) primed with IL-1β in osteoarthritic SW982 cells. @*METHODS@#SW982 cells were treated with interleukin (IL)-1β and tumor necrosis factor (TNF)-α to induce the OA phenotype. The effect of exosomes without priming (MSC-Exo) or with IL-1β priming (MSC-IL-Exo) was examined on the expression of pro- or anti-inflammatory factors, and the amount of IκBα was examined in SW982 cells. Exosomes were treated with RNase to remove RNA. The role of miR-147b was examined using a mimic and an inhibitor. @*RESULTS@#MSC-IL-Exo showed stronger inhibitory effects on the expression of pro-inflammatory cytokines (IL-1β, IL-6, and monocyte chemoattractant protein-1) than MSC-Exo. The expression of anti-inflammatory factors (SOCS3 and SOCS6) was enhanced by MSCs-IL-Exo. Priming with IL-1β increased RNA content in MSC-IL-Exo, and pretreatment with RNase abolished anti-inflammatory effect in SW982 cells. miR-147b was found in much larger amounts in MSC-IL-Exo than in MSC-Exo. The miR-147b mimic significantly inhibited the expression of inflammatory cytokines, while the miR-147b inhibitor only partially blocked the anti-inflammatory effect of MSC-IL-Exo. MSC-IL-Exo and miR-147b mimic inhibited the reduction of IκBα, an nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor, by IL-1β and TNF-α. @*CONCLUSION@#This study showed that MSC exosomes with IL-1β priming exhibit significantly enhanced anti-inflammatory activity in osteoarthritic SW982 cells. The effect of IL-1β-primed MSC exosomes is mediated by miRNAs such as miR-147b and involves inhibition of the NF-κB pathway.

Corneal Repair with Adhesive Cell Sheets of Fetal Cartilage-Derived Stem Cells

BACKGROUND@#Corneal scarring or disease may lead to severe corneal opacification and consequently, severe loss of vision due to the complete loss of corneal epithelial cells. We studied the use of epithelial cell sheets differentiated from fetal cartilage-derived stem cells (FCSC) to resurface damaged cornea. @*METHODS@#The FCSC were isolated from the femoral head of immature cartilage tissue. The ability of the FCSCs to differentiate into corneal epithelial cells was evaluated using differentiation media at 2 days and 7 days post-seeding. A sheet fabricated of FCSCs was also used for the differentiation assay. The results of the in vitro studies were evaluated by immunocytochemistry and Western blots for corneal epithelial cell markers (CK3/12 and Pax6) and limbal epithelial stem cell markers (ABCG2 and p63). To test the material in vivo, an FCSC-sheet was applied as a treatment in a chemically burned rabbit model. The healing ability was observed histologically one week after treatment. @*RESULTS@#The in vitro experiments showed morphological changes in the FCSCs at two and seven days of culture. The differentiated cells from the FCSCs or the FCSC-sheet expressed corneal epithelial cells markers. FCSC were create cell sheet that successfully differentiated into corneal epithelial cells and had sufficient adhesion so that it could be fused to host tissue after suture to the ocular surface with silk suture. The implanted cell sheet maintained its transparency and the cells were alive a week after implantation. @*CONCLUSION@#These results suggest that carrier-free sheets fabricated of FCSCs have the potential to repair damaged corneal surfaces.

Exosomes from IL-1b-Primed Mesenchymal Stem Cells Inhibited IL-1b- and TNF-a-Mediated Inflammatory Responses in Osteoarthritic SW982 Cells

BACKGROUND@#Exosomes from mesenchymal stem cells (MSCs) show anti-inflammatory effect on osteoarthritis (OA); however, their biological effect and mechanism are not yet clearly understood. This study investigated the anti-inflammatory effect and mechanism of MSC-derived exosomes (MSC-Exo) primed with IL-1β in osteoarthritic SW982 cells. @*METHODS@#SW982 cells were treated with interleukin (IL)-1β and tumor necrosis factor (TNF)-α to induce the OA phenotype. The effect of exosomes without priming (MSC-Exo) or with IL-1β priming (MSC-IL-Exo) was examined on the expression of pro- or anti-inflammatory factors, and the amount of IκBα was examined in SW982 cells. Exosomes were treated with RNase to remove RNA. The role of miR-147b was examined using a mimic and an inhibitor. @*RESULTS@#MSC-IL-Exo showed stronger inhibitory effects on the expression of pro-inflammatory cytokines (IL-1β, IL-6, and monocyte chemoattractant protein-1) than MSC-Exo. The expression of anti-inflammatory factors (SOCS3 and SOCS6) was enhanced by MSCs-IL-Exo. Priming with IL-1β increased RNA content in MSC-IL-Exo, and pretreatment with RNase abolished anti-inflammatory effect in SW982 cells. miR-147b was found in much larger amounts in MSC-IL-Exo than in MSC-Exo. The miR-147b mimic significantly inhibited the expression of inflammatory cytokines, while the miR-147b inhibitor only partially blocked the anti-inflammatory effect of MSC-IL-Exo. MSC-IL-Exo and miR-147b mimic inhibited the reduction of IκBα, an nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor, by IL-1β and TNF-α. @*CONCLUSION@#This study showed that MSC exosomes with IL-1β priming exhibit significantly enhanced anti-inflammatory activity in osteoarthritic SW982 cells. The effect of IL-1β-primed MSC exosomes is mediated by miRNAs such as miR-147b and involves inhibition of the NF-κB pathway.

Inhibitory Effect of Topical Cartilage Acellular Matrix Suspension Treatment on Neovascularization in a Rabbit Corneal Model

BACKGROUND@#The extracellular matrix (ECM) of articular cartilage has an inhibitory effect on vascularization, yet clinical utilization has been technically challenging. In this study, we aimed to fabricate a biologically functional ECM powder suspension from porcine articular cartilage that inhibits neovascularization (NV). @*METHODS@#The digested-cartilage acellular matrix (dg-CAM) was prepared by sequential processes of decellularization, enzymatic digestion and pulverization. Physicochemical properties of dg-CAM were compared with that of native cartilage tissue (NCT). Cellular interactions between human umbilical vein endothelial cells (HUVECs) and dg-CAM was evaluated with proliferation, migration and tube formation assays compared with that of type I collagen (COL) and bevacizumab, an anti-angiogenic drug. We then investigated the therapeutic potential of topical administration of dg-CAM suspension on the experimentally induced rabbit corneal NV model. @*RESULTS@#The dg-CAM released a significantly larger amount of soluble proteins than that of the NCT and showed an improved hydrophilic and dispersion properties. In contrast, the dg-CAM contained a large amount of collagen, glycosaminoglycans and anti-angiogenic molecules as much as the NCT. The inhibitory effect on NV of the dg-CAM was more prominent than that of COL and even comparable to that of bevacizumab in inhibiting the HUVECs. The therapeutic potential of the dg-CAM was comparable to that of bevacizumab in the rabbit corneal NV model by efficiently inhibiting neovessel formation of the injured cornea. @*CONCLUSION@#The current study developed a dg-CAM having anti-angiogenic properties, together with water-dispersible properties suitable for topical or minimally invasive application for prevention of vessel invasion.

In Vivo Bioreactor Using Cellulose Membrane Benefit Engineering Cartilage by Improving the Chondrogenesis and Modulating the Immune Response

BACKGROUND@#To regenerate tissue-engineered cartilage as a source of material for the restoration of cartilage defects, we used a human fetal cartilage progenitor cell pellet to improve chondrogenesis and modulation of the immune response in an In Vivo bioreactor (IVB) system. @*METHODS@#IVB was buried subcutaneously in the host and then implanted into a cartilage defect. The IVB was composed of a silicone tube and a cellulose nano pore-sized membrane. First, fetal cartilage progenitor cell pellets were cultured in vitro for 3 days, then cultured in vitro, subcutaneously, and in an IVB for 3 weeks. First, the components and liquidity of IVB fluid were evaluated, then the chondrogenesis and immunogenicity of the pellets were evaluated using gross observation, cell viability assays, histology, biochemical analysis, RT-PCR, and Western blots. Finally, cartilage repair and synovial inflammation were evaluated histologically. @*RESULTS@#The fluid color and transparency of the IVB were similar to synovial fluid (SF) and the components were closer to SF than serum. The IVB system not only promoted the synthesis of cartilage matrix and maintained the cartilage phenotype, it also delayed calcification compared to the subcutaneously implanted pellets. @*CONCLUSION@#The IVB adopted to study cell differentiation was effective in preventing host immune rejection.

Inhibitory Effect of Topical Cartilage Acellular Matrix Suspension Treatment on Neovascularization in a Rabbit Corneal Model

BACKGROUND@#The extracellular matrix (ECM) of articular cartilage has an inhibitory effect on vascularization, yet clinical utilization has been technically challenging. In this study, we aimed to fabricate a biologically functional ECM powder suspension from porcine articular cartilage that inhibits neovascularization (NV). @*METHODS@#The digested-cartilage acellular matrix (dg-CAM) was prepared by sequential processes of decellularization, enzymatic digestion and pulverization. Physicochemical properties of dg-CAM were compared with that of native cartilage tissue (NCT). Cellular interactions between human umbilical vein endothelial cells (HUVECs) and dg-CAM was evaluated with proliferation, migration and tube formation assays compared with that of type I collagen (COL) and bevacizumab, an anti-angiogenic drug. We then investigated the therapeutic potential of topical administration of dg-CAM suspension on the experimentally induced rabbit corneal NV model. @*RESULTS@#The dg-CAM released a significantly larger amount of soluble proteins than that of the NCT and showed an improved hydrophilic and dispersion properties. In contrast, the dg-CAM contained a large amount of collagen, glycosaminoglycans and anti-angiogenic molecules as much as the NCT. The inhibitory effect on NV of the dg-CAM was more prominent than that of COL and even comparable to that of bevacizumab in inhibiting the HUVECs. The therapeutic potential of the dg-CAM was comparable to that of bevacizumab in the rabbit corneal NV model by efficiently inhibiting neovessel formation of the injured cornea. @*CONCLUSION@#The current study developed a dg-CAM having anti-angiogenic properties, together with water-dispersible properties suitable for topical or minimally invasive application for prevention of vessel invasion.

Electrostatically Interactive Injectable Hydrogels for Drug Delivery

BACKGROUND: Several injectable hydrogels have been developed extensively for a broad range of biomedical applications. Injectable hydrogels forming in situ through the change in external stimuli have the distinct properties of easy management and minimal invasiveness, and thus provide the advantage of bypassing surgical procedures for administration resulting in better patient compliance. METHODS: The injectable in situ-forming hydrogels can be formed irreversibly or reversibly under physiological stimuli. Among several external stimuli that induce formation of hydrogels in situ, in this review, we focused on the electrostatic interactions as the most simple and interesting stimulus. RESULTS: Currently, numerous polyelectrolytes have been reported as potential electrostatically interactive in situ-forming hydrogels. In this review, a comprehensive overview of the rapidly developing electrostatically interactive in situ-forming hydrogels, which are produced by various anionic and cationic polyelectrolytes such as chitosan, celluloses, and alginates, has been outlined and summarized. Further, their biomedical applications have also been discussed. CONCLUSION: The review concludes with perspectives on the future of electrostatically interactive in situ-forming hydrogels.

Characterization of Human Fetal Cartilage Progenitor Cells During Long-Term Expansion in a Xeno-Free Medium

BACKGROUND: Stem cell therapy requires a serum-free and/or chemically-defined medium for commercialization, but it is difficult to find one that supports long-term expansion of cells without compromising their stemness, particularly for novel stem cells. METHODS: In this study, we tested the efficiency of StemPro® MSC SFM Xeno Free (SFM-XF), a serum-free medium, for the long-term expansion of human fetal cartilage-derived progenitor cells (hFCPCs) from three donors in comparison to that of the conventional α-Modified Eagle's Medium (α-MEM) supplemented with 10% fetal bovine serum (FBS). RESULTS: We found that SFM-XF supported the expansion of hFCPCs for up to 28–30 passages without significant changes in the doubling time, while α-MEM with 10% FBS showed a rapid increase in doubling time at 10–18 passages depending on the donor. Senescence of hFCPCs was not observed until passage 10 in both media but was induced in approximately 15 and 25% of cells at passage 20 in SFM-XF and α-MEM with 10% FBS, respectively. The colony forming ability of hFCPCs in SFX-XF was also comparable to that in α-MEM with 10% FBS. hFCPCs expressed pluripotency genes like Oct-4, Sox-2, Nanog, SCF, and SSEA4 at passage 20 and 31 in SFM-XF; however, this was not observed when cells were cultured in α-MEM with 10% FBS. The ability of hFCPCs to differentiate into three mesodermal lineages decreased gradually in both media but it was less significant in SFM-XF. Finally we found no chromosomal abnormality after long-term culture of hFCPCs until passage 17 by karyotype analysis. CONCLUSION: These results suggest that SFM-XF supports the long-term expansion of hFCPCs without significant phenotypic and chromosomal changes. This study have also shown that hFCPCs can be mass-produced in vitro, proving their commercial value as a novel source for developing cell therapies.

Three-Dimensional Spheroid Culture Increases Exosome Secretion from Mesenchymal Stem Cells

BACKGROUND: Mass production of exosomes is a prerequisite for their commercial utilization. This study investigated whether three-dimensional (3D) spheroid culture of mesenchymal stem cells (MSCs) could improve the production efficiency of exosomes and if so, what was the mechanism involved. METHODS: We adopted two models of 3D spheroid culture using the hanging-drop (3D-HD) and poly(2-hydroxyethyl methacrylate) (poly-HEMA) coating methods (3D-PH). The efficiency of exosome production from MSCs in the 3D spheroids was compared with that of monolayer culture in various conditions. We then investigated the mechanism of the 3D spheroid culture-induced increase in exosome production. RESULTS: The 3D-HD formed a single larger spheroid, while the 3D-PH formed multiple smaller ones. However, MSCs cultured on both types of spheroids produced significantly more exosomes than those cultured in conventional monolayer culture (2D). We then investigated the cause of the increased exosome production in terms of hypoxia within the 3D spheroids, high cell density, and non-adherent cell morphology. With increasing spheroid size, the efficiency of exosome production was the largest with the least amount of cells in both 3D-HD and 3D-PH. An increase in cell density in 2D culture (2D-H) was less efficient in exosome production than the conventional, lower cell density, 2D culture. Finally, when cells were plated at normal density on the poly-HEMA coated spheroids (3D-N-PH); they formed small aggregates of less than 10 cells and still produced more exosomes than those in the 2D culture when plated at the same density. We also found that the expression of F-actin was markedly reduced in the 3D-N-PH culture. CONCLUSION: These results suggested that 3D spheroid culture produces more exosomes than 2D culture and the non-adherent round cell morphology itself might be a causative factor. The result of the present study could provide useful information to develop an optimal process for the mass production of exosomes.

Mechanically Reinforced Extracellular Matrix Scaffold for Application of Cartilage Tissue Engineering

Scaffolds with cartilage-like environment and suitable physical properties are critical for tissue-engineered cartilage repair. In this study, decellularized porcine cartilage-derived extracellular matrix (ECM) was utilized to fabricate ECM scaffolds. Mechanically reinforced ECM scaffolds were developed by combining salt-leaching and crosslinking for cartilage repair. The developed scaffolds were investigated with respect to their physicochemical properties and their cartilage tissue formation ability. The mechanically reinforced ECM scaffold showed similar mechanical strength to that of synthetic PLGA scaffold and expressed higher levels of cartilage-specific markers compared to those expressed by the ECM scaffold prepared by simple freeze-drying. These results demonstrated that the physical properties of ECM-derived scaffolds could be influenced by fabrication method, which provides suitable environments for the growth of chondrocytes. By extension, this study suggests a promising approach of natural biomaterials in cartilage tissue engineering.

Nondestructive Assessment of Glycosaminoglycans in Engineered Cartilages Using Hexabrix-Enhanced Micro-Computed Tomography

It is very useful to evaluate the content and 3D distribution of extracellular matrix non-destructively in tissue engineering. This study evaluated the feasibility of using micro-computed tomography (µCT) with Hexabrix to measure quantitatively sulfated glycosaminoglycans (GAGs) of engineered cartilage. Rabbit chondrocytes at passage 2 were used to produce artificial cartilages in polyglycolic acid scaffolds in vitro. Engineered cartilages were incubated with Hexabrix 320 for 20 min and analyzed via µCT scanning. The number of voxels in the 2D and 3D scanning images were counted to estimate the amount of sulfated GAGs. The optimal threshold value for quantification was determined by regression analysis. The 2D µCT images of an engineered cartilage showed positive correlation with the histological image of Safranin-O staining. Quantitative data obtained with the 3D µCT images of 14 engineered cartilages showed strong correlation with sulfated GAGs contents obtained by biochemical analysis (R² = 0.883, p < 0.001). Repeated exposure of engineered cartilages to Hexabrix 320 and µCT scanning did not significantly affect cell viability, total DNA content, or the total content of sulfated GAGs. We conclude that µCT imaging using Hexabrix 320 provides high spatial resolution and sensitivity to assess the content and 3D distribution of sulfated GAGs in engineered cartilages. It is expected to be a valuable tool to evaluate the quality of engineered cartilage for commercial development in the future.

Development of Printable Natural Cartilage Matrix Bioink for 3D Printing of Irregular Tissue Shape

The extracellular matrix (ECM) is known to provide instructive cues for cell attachment, proliferation, differentiation, and ultimately tissue regeneration. The use of decellularized ECM scaffolds for regenerative-medicine approaches is rapidly expanding. In this study, cartilage acellular matrix (CAM)-based bioink was developed to fabricate functional biomolecule-containing scaffolds. The CAM provides an adequate cartilage tissue–favorable environment for chondrogenic differentiation of cells. Conventional manufacturing techniques such as salt leaching, solvent casting, gas forming, and freeze drying when applied to CAM-based scaffolds cannot precisely control the scaffold geometry for mimicking tissue shape. As an alternative to the scaffold fabrication methods, 3D printing was recently introduced in the field of tissue engineering. 3D printing may better control the internal microstructure and external appearance because of the computer-assisted construction process. Hence, applications of the 3D printing technology to tissue engineering are rapidly proliferating. Therefore, printable ECM-based bioink should be developed for 3D structure stratification. The aim of this study was to develop printable natural CAM bioink for 3D printing of a tissue of irregular shape. Silk fibroin was chosen to support the printing of the CAM powder because it can be physically cross-linked and its viscosity can be easily controlled. The newly developed CAM-silk bioink was evaluated regarding printability, cell viability, and tissue differentiation. Moreover, we successfully demonstrated 3D printing of a cartilage-shaped scaffold using only this CAM-silk bioink. Future studies should assess the efficacy of in vivo implantation of 3D-printed cartilage-shaped scaffolds.

Advances in Three-Dimensional Bioprinting for Hard Tissue Engineering

The need for organ and tissue regeneration in patients continues to increase because of a scarcity of donors, as well as biocompatibility issues in transplant immune rejection. To address this, scientists have investigated artificial tissues as an alternative to transplantation. Three-dimensional (3D) bioprinting technology is an additive manufacturing method that can be used for the fabrication of 3D functional tissues or organs. This technology promises to replicate the complex architecture of structures in natural tissue. To date, 3D bioprinting strategies have confirmed their potential practice in regenerative medicine to fabricate the transplantable hard tissues, including cartilage and bone. However, 3D bioprinting approaches still have unsolved challenges to realize 3D hard tissues. In this manuscript, the current technical development, challenges, and future prospects of 3D bioprinting for engineering hard tissues are reviewed.

Repair of Partial Thickness Cartilage Defects Using Cartilage Extracellular Matrix Membrane-Based Chondrocyte Delivery System in Human Ex Vivo Model

Treatment options for partial thickness cartilage defects are limited. The purpose of this study was to evaluate the efficacy of the chondrocyte-seeded cartilage extracellular matrix membrane in repairing partial thickness cartilage defects. First, the potential of the membrane as an effective cell carrier was investigated. Secondly, we have applied the chondrocyte-seeded membrane in an ex vivo, partial thickness defect model to analyze its repair potential. After culture of chondrocytes on the membrane in vitro, cell viability assay, cell seeding yield calculation and cell transfer assay were done. Cell carrying ability of the membrane was also tested by seeding different densities of cells. Partial defects were created on human cartilage tissue explants. Cell-seeded membranes were applied using a modified autologous chondrocyte implantation technique on the defects and implanted subcutaneously in nude mice for 2 and 4 weeks. In vitro data showed cell viability and seeding yield comparable to standard culture dishes. Time dependent cell transfer from the membrane was observed. Membranes supported various densities of cells. Ex vivo data showed hyaline-like cartilage tissue repair, integrated on the defect by 4 weeks. Overall, chondrocyte-seeded cartilage extracellular membranes may be an effective and feasible treatment strategy for the repair of partial thickness cartilage defects.

A superficial hyperechoic band in human articular cartilage on ultrasonography with histological correlation: preliminary observations

PURPOSE: To demonstrate the superficial hyperechoic band (SHEB) in articular cartilage by using ultrasonography (US) and to assess its correlation with histological images. METHODS: In total, 47 regions of interest (ROIs) were analyzed from six tibial osteochondral specimens (OCSs) that were obtained after total knee arthroplasty. Ultrasonograms were obtained for each OCS. Then, matching histological sections from all specimens were obtained for comparison with the ultrasonograms. Two types of histological staining were used: Safranin-O stain (SO) to identify glycosaminoglycans (GAG) and Masson's trichrome stain (MT) to identify collagen. In step 1, two observers evaluated whether there was an SHEB in each ROI. In step 2, the two observers evaluated which histological staining method correlated better with the SHEB by using the ImageJ software. RESULTS: In step 1 of the analysis, 20 out of 47 ROIs showed an SHEB (42.6%, kappa=0.579). Step 2 showed that the SHEB correlated significantly better with the topographical variation in stainability in SO staining, indicating the GAG distribution, than with MT staining, indicating the collagen distribution (P<0.05, kappa=0.722). CONCLUSION: The SHEB that is frequently seen in human articular cartilage on high-resolution US correlated better with variations in SO staining than with variations in MT staining. Thus, we suggest that a SHEB is predominantly related to changes in GAG. Identifying an SHEB by US is a promising method for assessing the thickness of articular cartilage or for monitoring early osteoarthritis.

Bilateral Occurrence and Morphologic Analysis of Complete Discoid Lateral Meniscus

PURPOSE: The aim of the study was to investigate and analyze bilateral incidence and morphology of complete discoid lateral meniscus (DLM) with possible relation to tears and symptoms in knee joints. MATERIALS AND METHODS: Thirty-eight consecutive patients with symptomatic or already-torn complete DLM on magnetic resonance imaging in a unilateral knee underwent diagnostic arthroscopy on both knee joints upon agreement. The presence and shape of complete DLM as well as presence and pattern of tear were recorded accordingly. RESULTS: In total, 89.5% (34 of 38 patients) showed bilateral complete DLM, and 84.2% yielded bilateralism with identical shape. Cape-slab was the most frequent shape, comprising 68.8% of patients with identically-shaped bilateral DLM overall. Tear patterns were more frequent, in the order of longitudinal, simple horizontal, radial, and degenerative; however, the morphological shape of complete DLM was not significantly related to tear incidence or pattern. Meniscus tears and knee symptoms occurred in the contralateral knee with incidences of 32.4% and 26.5% in patients with bilateral complete DLM, respectively. CONCLUSION: Based on these findings, more aggressive warning on the presence of discoid pathology and the need for evaluation on the contralateral knee should be considered during consultation with patients with symptomatic complete DLM in a unilateral knee in the outpatient clinic.

Stem cells in musculoskeletal system for clinical application

Mesenchymal stem cells (MSCs) play a crucial role in the proliferation and differentiation of human tissue such as bone, cartilage, muscle, fat, and fibroblasts. Various surgical techniques have been developed for the repair of the musculoskeletal system, but they can be often limited. Thus, the efforts that can be employed in treatment for MSCs population of degenerative musculoskeletal diseases are underway. Patients who have a musculoskeletal disease with low numbers of functional MSCs will be treated using a focus on cell-based therapy. The ideal clinical application is to engineer material/scaffolds that are capable of delivering therapeutic cells that can regenerate and repair damaged tissue. The ability related to MSCs differentiation using biomaterial systems offers a minimally invasive therapeutic option for diseases of the musculoskelecal system and tissue repair. Understanding the natural mechanisms for this delivery is essential to the success of tissue engineering biomaterials that deliver therapeutic cells.

The Significance of Bone Scan and Classificationin Young Adult Osgood-Schlatter Disease

PURPOSE: We retrospectively classified the young adult Osgood-Schlatter disease by plain radiography and accessed the relationship between bone scan results and symptom duration. MATERIALS AND METHODS: From 2004 to 2007, young adults with symptoms of Osgood-Schlatter disease were included in the study. The patients were classified into 3 groups, protrusion, cleft and ossicle, according to their radiographic results. All patients had bone scan exams, we analyzed the correlation between the bone scan results and the duration of symptoms. RESULTS: All patients were male with average age of 19.8 (18.5~22.0) years old. Out of 59 patients, 27 were bilateral. Of 86 knee joints, 36 came out positive with bone scan. Positive bone scan rate was 11.1% in protrusion type, 40.0% in cleft type and 61.4% in ossicle type. The pain persisted longer in ossicle type than the others. The symptom duration correlated with the bone scan results. CONCLUSION: We classified young adult Osgood Schlatter disease as three types. The ossicle type of Osgood-Schlatter disease has longer symptom duration, which correlates with the bone scan results. The bone scan result can be one of reliable reference factors for the treatment of young adult Osgood-Schlatter disease.

Cartilage Repair Using Mesenchymal Stem Cells

Articular cartilage defect rarely heals spontaneously due to its avascularity and low cellularity. Even small articular cartilage defects can develop into osteoarthritis, and subsequently, its management has been a major clinical concern. Although there are several treatment options for cartilage defect, no treatment has been established as a gold standard procedure. Bone marrow stimulation techniques which is equivalent to microfracture these days has been adapted as first line treatment, attributed to their technical easiness and minimal invasiveness to patients. However, this procedure has limitation in reproducing hyaline cartilage, so recent cell-based therapies using autologous chondrocytes or mesenchymal stem cells have drawn particular attention. MSCs regardless of its origin have shown significant potential for chondrogenesis. Novel approaches using MSCs as an alternative cell source for patient derived chondrocytes are currently on trial. In this review, stem cells from various origins considered as cell sources and potential application of mesenchymal stem cells to promote cartilage repair will be discussed. While differentiation of stem cell can be well controlled in vitro, it is not easy to predict the course of differentiation when the stem cell is transplanted. Some novel methods using physical stimulation and material based techniques for differentiation control are introduced in this context. Such differentiation control will be beneficial when it is adapted before transplantation. We call it preconditioning.