Improving the genome editing efficiency of CRISPR/Cas9 in Arabidopsis and Medicago truncatula.

MAIN CONCLUSION: An improved CRISPR/Cas9 system with the Arabidopsis UBQ10 promoter-driven Cas9 exhibits consistently high mutation efficiency in Arabidopsis and M. truncatula. CRISPR/Cas9 is a powerful genome editing technology that has been applied in several crop species for trait improvement due to its simplicity, versatility, and specificity. However, the mutation efficiency of CRISPR/Cas9 in Arabidopsis and M. truncatula (Mt) is still challenging and inconsistent. To analyze the functionality of the CRISPR/Cas9 system in two model dicot species, four different promoter-driven Cas9 systems to target phytoene desaturase (PDS) genes were designed. Agrobacterium-mediated transformation was used for the delivery of constructed vectors to host plants. Phenotypic and genotypic analyses revealed that the Arabidopsis UBQ10 promoter-driven Cas9 significantly improves the mutation efficiency to 95% in Arabidopsis and 70% in M. truncatula. Moreover, the UBQ10-Cas9 system yielded 11% homozygous mutants in the T1 generation in Arabidopsis. Sequencing analyses of mutation events indicated that single-nucleotide insertions are the most frequent events in Arabidopsis, whereas multi-nucleotide deletions are dominant in bi-allelic and mono-allelic homozygous mutants in M. truncatula. Taken together, the UBQ10 promoter facilitates the best improvement in the CRISPR/Cas9 efficiency in PDS gene editing, followed by the EC1.2 promoter. Consistently, the improved UBQ10-Cas9 vector highly enhanced the mutation efficiency by four-fold over the commonly used 35S promoter in both dicot species.

DNA-free genome editing with preassembled CRISPR/Cas9 ribonucleoproteins in plants.

Processes of traditional trait development in plants depend on genetic variations derived from spontaneous mutation or artificial random mutagenesis. Limited availability of desired traits in crossable relatives or failure to generate the wanted phenotypes by random mutagenesis led to develop innovative breeding methods that are truly cross-species and precise. To this end, we devised novel methods of precise genome engineering that are characterized to use pre-assembled CRISPR/Cas9 ribonucleoprotein (RNP) complex instead of using nucleic ands or Agrobacterium. We found that our methods successfully engineered plant genomes without leaving any foreign DNA footprint in the genomes. To facilitate introduction of RNP into plant nucleus, we first obtained protoplasts after removing the transfection barrier, cell wall. Whole plants were regenerated from the single cell of protoplasts that has been engineered with the RNP. Pending the improved way of protoplast regeneration technology especially in crop plants, our methods should help develop novel traits in crop plants in relatively short time with safe and precise way.

Two distinct cellular pathways leading to endothelial cell cytotoxicity by silica nanoparticle size.

BACKGROUND: Silica nanoparticles (SiNPs) are widely used for biosensing and diagnostics, and for the targeted delivery of therapeutic agents. Safety concerns about the biomedical and clinical applications of SiNPs have been raised, necessitating analysis of the effects of their intrinsic properties, such as sizes, shapes, and surface physicochemical characteristics, on human health to minimize risk in biomedical applications. In particular, SiNP size-associated toxicological effects, and the underlying molecular mechanisms in the vascular endothelium remain unclear. This study aimed to elucidate the detailed mechanisms underlying the cellular response to exposure to trace amounts of SiNPs and to determine applicable size criteria for biomedical application. METHODS: To clarify whether these SiNP-mediated cytotoxicity due to induction of apoptosis or necrosis, human ECs were treated with SiNPs of four different non-overlapping sizes under low serum-containing condition, stained with annexin V and propidium iodide (PI), and subjected to flow cytometric analysis (FACS). Two types of cell death mechanisms were assessed in terms of production of reactive oxygen species (ROS), endoplasmic reticulum (ER) stress induction, and autophagy activity. RESULTS: Spherical SiNPs had a diameter of 21.8 nm; this was further increased to 31.4, 42.9, and 56.7 nm. Hence, we investigated these effects in human endothelial cells (ECs) treated with these nanoparticles under overlap- or agglomerate-free conditions. The 20-nm SiNPs, but not SiNPs of other sizes, significantly induced apoptosis and necrosis. Surprisingly, the two types of cell death occurred independently and through different mechanisms. Apoptotic cell death resulted from ROS-mediated ER stress. Furthermore, autophagy-mediated necrotic cell death was induced through the PI3K/AKT/eNOS signaling axis. Together, the present results indicate that SiNPs within a diameter of < 20-nm pose greater risks to cells in terms of cytotoxic effects. CONCLUSION: These data provide novel insights into the size-dependence of the cytotoxic effects of silica nanoparticles and the underlying molecular mechanisms. The findings are expected to inform the applicable size range of SiNPs to ensure their safety in biomedical and clinical applications.

A class II KNOX gene, KNOX4, controls seed physical dormancy.

Physical dormancy of seed is an adaptive trait that widely exists in higher plants. This kind of dormancy is caused by a water-impermeable layer that blocks water and oxygen from the surrounding environment and keeps embryos in a viable status for a long time. Most of the work on hardseededness has focused on morphological structure and phenolic content of seed coat. The molecular mechanism underlying physical dormancy remains largely elusive. By screening a large number of Tnt1 retrotransposon-tagged Medicago truncatula lines, we identified nondormant seed mutants from this model legume species. Unlike wild-type hard seeds exhibiting physical dormancy, the mature mutant seeds imbibed water quickly and germinated easily, without the need for scarification. Microscopic observations of cross sections showed that the mutant phenotype was caused by a dysfunctional palisade cuticle layer in the seed coat. Chemical analysis found differences in lipid monomer composition between the wild-type and mutant seed coats. Genetic and molecular analyses revealed that a class II KNOTTED-like homeobox (KNOXII) gene, KNOX4, was responsible for the loss of physical dormancy in the seeds of the mutants. Microarray and chromatin immunoprecipitation analyses identified CYP86A, a gene associated with cutin biosynthesis, as one of the downstream target genes of KNOX4 This study elucidated a novel molecular mechanism of physical dormancy and revealed a new role of class II KNOX genes. Furthermore, KNOX4-like genes exist widely in seed plants but are lacking in nonseed species, indicating that KNOX4 may have diverged from the other KNOXII genes during the evolution of seed plants.

Effect of Semi-Fluorinated Alkyl Side Chains on Conjugated Polymers with Planar Backbone in Organic Field-Effect Transistors.

Newly synthesized donor-acceptor (D-A) type of conjugated copolymer (PCTV-BTzF) with semi-fluorinated alkyl side chains, which has good solubility in common organic solvents, is described. Unlike polymers with hydrocarbon-based alkyl side chains, semi-fluorocabonated polymer leads to intriguing results. First, the self-organization behavior of the semi-fluoroalkyl side chains by the self-aggregate propensity between hydrocarbon and fluorocarbon induces patterned microstructural morphology in polymer films; second, it dominates the molecular orientation of polymers with planar back structure. Such unusual properties of the polymer with semi-fluoroalkyl side chains compared to that with the hydrocarbon ones are verified and characterized though various systematic characterizations, including temperature-dependent UV-Vis absorption spectroscopy, atomic force microscopy, and 2D-grazing incident X-ray diffraction measurement. As a result, PCTV-BTzF-based OFETs show the maximum p-type field-effect mobility of 1.02 cm2  V-1  s-1 in the 200 °C annealed films.

Redox-Triggered Coloration Mechanism of Electrically Tunable Colloidal Photonic Crystals.

Electrically tunable colloidal photonic crystals (ETPCs) have been investigated because of several merits such as easy color tunability, no discoloration, and clear color. The coloration mechanism of ETPCs has been explained in terms of only the electric field. Herein, we report on a new mechanism: electric field plus redox reaction. Specifically, the coloration behavior of ETPCs was investigated under electrically conductive or insulated conditions using current-voltage, cyclic voltammetry, and zeta potential measurements, as well as scanning electron microscopy. Electrophoretic movement of ETPC particles toward the positive electrode was caused by the electric field due to the particles' negative surface charge. At the positive electrode, ETPC particles lost their electrons and formed a colloidal crystal structure. Finally, an ETPC transparent tube device was constructed to demonstrate the coloration mechanism.

Conductive network formation of carbon nanotubes in elastic polymer microfibers and its effect on the electrical conductance: Experiment and simulation.

We investigate how the electrical conductance of microfibers (made of polymers and conductive nanofillers) decreases upon uniaxial deformation by performing both experiments and simulations. Even though various elastic conductors have been developed due to promising applications for deformable electronic devices, the mechanism at a molecular level for electrical conductance change has remained elusive. Previous studies proposed that the decrease in electrical conductance would result from changes in either distances or contact numbers between conductive fillers. In this work, we prepare microfibers of single walled carbon nanotubes (SWCNTs)/polyvinyl alcohol composites and investigate the electrical conductance and the orientation of SWCNTs upon uniaxial deformation. We also perform extensive Monte Carlo simulations, which reproduce experimental results for the relative decrease in conductance and the SWCNTs orientation. We investigate the electrical networks of SWCNTs in microfibers and find that the decrease in the electrical conductance upon uniaxial deformation should be attributed to a subtle change in the topological structure of the electrical network.

Loss of NDRG2 promotes epithelial-mesenchymal transition of gallbladder carcinoma cells through MMP-19-mediated Slug expression.

BACKGROUND & AIMS: Gallbladder carcinoma (GBC) is the most common malignancy of the biliary tract and one of the most lethal forms of human cancer. However, there is limited information about the molecular pathogenesis of GBC. Here, we examined the functional role of the tumor suppressor N-myc downstream-regulated gene 2 (NDRG2) and the underlying molecular mechanisms of disease progression in GBC. METHODS: Clinical correlations between NDRG2 expression and clinicopathological factors were determined by immunohistochemical analysis of tumor tissues from 86 GBC patients. Biological functions of NDRG2 and NDRG2-mediated signaling pathways were determined in GBC cell lines with NDRG2 knockdown or overexpression. RESULTS: Loss of NDRG2 expression was an independent predictor of decreased survival and was significantly associated with a more advanced T stage, higher cellular grade, and lymphatic invasion in patients with GBC. GBC cells with loss of NDRG2 expression showed significantly enhanced proliferation, migration, and invasiveness in vitro, and tumor growth and metastasis in vivo. Loss of NDRG2 induced the expression of matrix metalloproteinase-19 (MMP-19), which regulated the expression of Slug at the transcriptional level. In addition, MMP-19-induced Slug, increased the expression of a receptor tyrosine kinase, Axl, which maintained Slug expression through a positive feedback loop, and stabilized epithelial-mesenchymal transition of GBC cells. CONCLUSIONS: The results of our study help to explain why the loss of NDRG2 expression is closely correlated with malignancy of GBC. These results strongly suggest that NDRG2 could be a favorable prognostic indicator and promising target for therapeutic agents against GBC.

Output Performance Enhanced Triboelectric Nanogenerators Induced by Magnetic Ink Trapping Property Act as Wearable Sensors.

The demand for clean-energy collection has gradually increased in recent years, making triboelectric nanogenerators a promising research field, because of their advantages in convenient manufacturing, diversified materials, and diverse synthesis and modification possibilities. However, recent studies indicate that charge decay, a major limiting factor in the triboelectric output, prevents the induced charge from combining with the bottom electrode, leading to charge loss. The use of charge-trapping sites to retain the induced charge generated during the friction process is an important solution in the field of triboelectric nanogenerator research. This study proposes the use of an elastic ink with macroscopic magnetism as trapping sites by coating the ink as dots between the polytetrafluoroethylene (PTFE) dielectric layer and the electrode layer. Nickel particles in the magnetic ink are doped into the system as microcapacitors, which prevent the combination of the friction layer and induced charges on the back electrode. Because the nickel itself can be used as a charge-potential trap to capture the charge introduced by the charge-injection process, the charge can be maintained for a long time and achieve a long-term high-output state. The output voltage was more than 6 times that of the reference group without the magnetic-ink coating after 3 h. The results provide a reference direction for research on preventing charge decay and trapping charges in triboelectric nanogenerators.

Enhanced N-type Semiconducting Performance of Asymmetric Monochlorinated Isoindigo-based Semiregioregular Polymers under Dynamic Forces.

The asymmetric monochlorination strategy not only effectively addresses the steric issues in conventional dichlorination but also enables the development of promising acceptor units and semiregioregular polymers. Herein, monochlorinated isoindigo (1CIID) is successfully designed and synthesized by selectively introducing single chlorine (Cl) atoms. Furthermore, the 1CIID copolymerizes with two donor counterparts, centrosymmetric 2,2'-bithiophene (2T) and axisymmetric 4,7-di(thiophen-2-yl)benzo[1,2,5]thiadiazole (DTBT), forming two polymers, P1CIID-2T and P1CIID-DTBT. These polymers exhibit notable differences in backbone linearity and dipole moments, influenced by the symmetry of their donor counterparts. In particular, P1CIID-2T, which contains a centrosymmetric 2T unit, demonstrates a linear backbone and a significant dipole moment of 10.20 D. These properties contribute to the favorable film morphology of P1CIID-2T, characterized by highly ordered crystallinity in the presence of fifth-order (500) X-ray diffraction peaks. Notably, P1CIID-2T exhibits a significant improvement in molecular alignment under dynamic force, resulting in over 8-fold improvement in the performance of organic field-effect transistor (OFET) devices, with superior electron mobility up to 1.22 cm2 V-1 s-1. This study represents the first synthesis of asymmetric monochlorinated isoindigo-based conjugated polymers, highlighting the potential of asymmetric monochlorination for developing n-type semiconducting polymers. Moreover, our findings provide valuable insights into the relationship between the molecular structure and properties.

Highly efficient hybrid energy generator: coupled organic photovoltaic device and randomly oriented electrospun poly(vinylidene fluoride) nanofiber.

A hybrid architecture consisting of an inverted organic photovoltaic device and a randomly-oriented electrospun PVDF piezoelectric device was fabricated as a highly-efficient energy generator. It uses the inverted photovoltaic device with coupled electrospun PVDF nanofibers as tandem structure to convert solar and mechanical vibrations energy to electricity simultaneously or individually. The power conversion efficiency of the photovoltaic device was also significantly improved up to 4.72% by optimized processes such as intrinsic ZnO, MoO3 and active layer. A simple electrospinning method with the two electrode technique was adopted to achieve a high voltage of - 300 mV in PVDF piezoelectric fibers. Highly-efficient HEG using voltage adder circuit provides the conceptual possibility of realizing multi-functional energy generator whenever and wherever various energy sources are available.

Primary pyomyositis and uveitis in a cat.

A 6-year-old neutered male Siamese cat was referred for investigation of hindlimb ataxia and blindness of 2 weeks' duration. A swollen right hind limb, with no history of trauma, and no evidence of an external wound, was observed on physical examination. Ophthalmic examination revealed bilateral absence of the menace response and changes consistent with uveitis. Blood tests identified changes consistent with inflammation including serum amyloid A elevation. Infectious disease testing was negative. Degenerate neutrophils and bacterial cocci were detected on fine needle aspiration cytology of the affected limb. Thoracic radiography and abdominal ultrasonography identified no abnormalities. Primary pyomyositis was suspected and clindamycin was prescribed following Penrose drain tube placement. In addition, eye drops containing tobramycin, atropine, and prednisolone were administered. The clinical signs and serum amyloid A level were markedly improved after 5 days of treatment. Based on the medical history and lack of other findings, the uveitis was suspected to be secondary to the pyomyositis. The clinical signs resolved completely, and no recurrence was reported within a 6-month follow-up period. To the best of our knowledge, primary pyomyositis with uveitis has not been previously reported in cats.

Suspected Cerebral Salt Wasting Syndrome with Cervical Spinal Lesion in a Domestic Shorthair Cat.

A 12-year-old spayed female domestic short cat was presented with tetraplegia. The cat also showed signs of hyponatremia and dehydration, which were rapidly corrected by intravenous fluid infusion. Based on thorough physical and neurological examinations, the patient was suspected of having an intracranial disease. MRI revealed a high-signal T2 image of the bilateral parietal cerebral cortical gray matter junction, which is associated with fast electrolyte calibration, and a high-signal T2 image of the C2 spinal cord ventral area, which is associated with ischemic myelopathy. The cat reappeared three days later due to anorexia. Laboratory examinations revealed that the cat was clinically dehydrated and exhibited hyponatremia. Other causes of hyponatremia were excluded through history-taking, laboratory examination, imaging, and therapeutic response to fluid therapy, except for cerebral salt-wasting syndrome (CSWS). The cat was discharged 3 days after the start of fludrocortisone therapy with electrolytes within the normal range. Magnetic resonance imaging (MRI) was performed again 1 month after hospitalization, and the cerebral lesion disappeared, but the spinal cord lesion worsened compared to the previous image. The patient was euthanized due to the progression of the spinal lesion, with a poor prognosis and poor quality of life. This is the first case of suspected CSWS with a cervical spinal lesion in a cat.

Off-Label Use of Crisdesalazine (GedaCure) in Meningoencephalitis in Two Dogs.

An 8-year-old, castrated male Shih-tzu dog (Case 1) showing ataxia and gait disorder was referred for neurological examination and magnetic resonance imaging. Through comprehensive examinations, the patient was tentatively diagnosed with meningoencephalitis of unknown origin (MUO) and treatment with prednisolone and cytosine arabinoside was started. The symptoms were improving with immunosuppressive treatment. However, severe bacterial cystitis occurred and we could not avoid tapering off prednisolone. Then, neurological signs recurred. Therefore, we added crisdesalazine, which allowed us to reduce the daily dosage of immunosuppressants easily. In another case, a 4-year-old, spayed female Yorkshire terrier dog (Case 2) was referred to our hospital showing a head tilt, circling, and loss of the menace reflex. The patient was tentatively diagnosed with MUO and treatment with some immunosuppressants was attempted. The clinical symptoms improved, but the alleviation was inadequate. Thus, we added crisdesalazine. The neurological signs then markedly improved. Moreover, the drugs could be tapered off more easily than before. Crisdesalazine is a novel drug that has antioxidant and anti-inflammatory action in brain disease and is used particularly for dementia. In this paper, we tried an off-label use of this drug in canine MUO patients, and found that it had, in these two patients, additional therapeutic effects on the MUO.

Long-wave infrared transparent sulfur polymers enabled by symmetric thiol cross-linker.

Infrared (IR) transmissive polymeric materials for optical elements require a balance between their optical properties, including refractive index (n) and IR transparency, and thermal properties such as glass transition temperature (Tg). Achieving both a high refractive index (n) and IR transparency in polymer materials is a very difficult challenge. In particular, there are significant complexities and considerations to obtaining organic materials that transmit in the long-wave infrared (LWIR) region, because of high optical losses due to the IR absorption of the organic molecules. Our differentiated strategy to extend the frontiers of LWIR transparency is to reduce the IR absorption of the organic moieties. The proposed approach synthesized a sulfur copolymer via the inverse vulcanization of 1,3,5-benzenetrithiol (BTT), which has a relatively simple IR absorption because of its symmetric structure, and elemental sulfur, which is mostly IR inactive. This strategy resulted in approximately 1 mm thick windows with an ultrahigh refractive index (nav > 1.9) and high mid-wave infrared (MWIR) and LWIR transmission, without any significant decline in thermal properties. Furthermore, we demonstrated that our IR transmissive material was sufficiently competitive with widely used optical inorganic and polymeric materials.

Amplified Performance of Charge Accumulation and Trapping Induced by Enhancing the Dielectric Constant via the Cyano Group of 3D-Structured Textile for a Triboelectric Multi-Modal Sensor.

To further improve the output performance of triboelectric devices, reducing charge attenuation and loss has become a hot research topic. Particularly, textiles have emerged as one of the promising research directions for triboelectric devices owing to their special internal structure and large specific surface area. In the present work, polyacrylonitrile fibers are fabricated with two distinct structures to provide a higher dielectric constant due to the strong polar properties brought about by higher dipole moment of the CN group. In addition, the complex and closely connected structure of the textile increases specific internal surface area. As a friction layer, the output voltage is shown to increase to 625% of the initial value (from 8 to 60 V) after the application of friction for a short time due to accumulation property. When acting as a trapping layer, the charge loss after injection is effectively prevented due to excellent charge trapping effect. After 24 h, the triboelectric output performance remains at ≈70% of the initial value (decreasing from 320 to 220 V), which is more than 20 times that of the polytetrafluoroethylene film, which decreases from 125 to 19 V. The device is realized for the advanced application of multi-modal sensors.

Detection of Red Pepper Powder Adulteration with Allura Red and Red Pepper Seeds Using Hyperspectral Imaging.

This study used shortwave infrared (SWIR) technology to determine whether red pepper powder was artificially adulterated with Allura Red and red pepper seeds. First, the ratio of red pepper pericarp to seed was adjusted to 100:0 (P100), 75:25 (P75), 50:50 (P50), 25:75 (P25), or 0:100 (P0), and Allura Red was added to the red pepper pericarp/seed mixture at 0.05% (A), 0.1% (B), and 0.15% (C). The results of principal component analysis (PCA) using the L, a, and b values; hue angle; and chroma showed that the pure pericarp powder (P100) was not easily distinguished from some adulterated samples (P50A-C, P75A-C, and P100B,C). Adulterated red pepper powder was detected by applying machine learning techniques, including linear discriminant analysis (LDA), linear support vector machine (LSVM), and k-nearest neighbor (KNN), based on spectra obtained from SWIR (1,000-1,700 nm). Linear discriminant analysis determined adulteration with 100% accuracy when the samples were divided into four categories (acceptable, adulterated by Allura Red, adulterated by seeds, and adulterated by seeds and Allura Red). The application of SWIR technology and machine learning detects adulteration with Allura Red and seeds in red pepper powder.

TGF-ß and SHH Regulate Pluripotent Stem Cell Differentiation into Brain Microvascular Endothelial Cells in Generating an In Vitro Blood-Brain Barrier Model.

Blood-brain barrier (BBB) models are important tools for studying CNS drug delivery, brain development, and brain disease. In vitro BBB models have been obtained from animals and immortalized cell lines; however, brain microvascular endothelial cells (BMECs) derived from them have several limitations. Furthermore, obtaining mature brain microvascular endothelial-like cells (BME-like cells) from human pluripotent stem cells (hPSCs) with desirable properties for establishing BBB models has been challenging. Here, we developed an efficient method for differentiating hPSCs into BMECs that are amenable to the development and application of human BBB models. The established conditions provided an environment similar to that occurring during BBB differentiation in the presence of the co-differentiating neural cell population by the modulation of TGF-ß and SHH signaling. The developed BME-like cells showed well-organized tight junctions, appropriate expression of nutrient transporters, and polarized efflux transporter activity. In addition, BME-like cells responded to astrocytes, acquiring substantial barrier properties as measured by transendothelial electrical resistance. Moreover, the BME-like cells exhibited an immune quiescent property of BBB endothelial cells by decreasing the expression of adhesion molecules. Therefore, our novel cellular platform could be useful for drug screening and the development of brain-permeable pharmaceuticals.

OsPUB15, an E3 ubiquitin ligase, functions to reduce cellular oxidative stress during seedling establishment.

The plant U-box (PUB) protein functions as an E3 ligase to poly-ubiquitinate a target protein for its degradation or post-translational modification. Here, we report functional roles for OsPUB15, which encodes a cytosolic U-box protein in the class-II PUB family. Self-ubiquitination assays showed that bacterially expressed MBP-OsPUB15 protein has E3 ubiquitin ligase activity. A T-DNA insertional mutation in OsPUB15 caused severe growth retardation and a seedling-lethal phenotype. Mutant seeds did not produce primary roots, and their shoot development was significantly delayed. Transgenic plants expressing the OsPUB15 antisense transcript phenocopied these mutant characters. The abnormal phenotypes were partially rescued by two antioxidants, catechin and ascorbic acid. Germinating seeds in the dark also recovered the rootless defect. Levels of H2O2 and oxidized proteins were higher in the knock-out mutant compared with the wild type. OsPUB15 transcript levels were increased upon H2O2, salt and drought stresses; plants overexpressing the gene grew better than the wild type under high salinity. These results indicate that PUB15 is a regulator that reduces reactive oxygen species (ROS) stress and cell death.

Generation of human induced pluripotent stem cells from osteoarthritis patient-derived synovial cells.

OBJECTIVE: This study was undertaken to generate and characterize human induced pluripotent stem cells (PSCs) from patients with osteoarthritis (OA) and to examine whether these cells can be developed into disease-relevant cell types for use in disease modeling and drug discovery. METHODS: Human synovial cells isolated from two 71-year-old women with advanced OA were characterized and reprogrammed into induced PSCs by ectopic expression of 4 transcription factors (Oct-4, SOX2, Klf4, and c-Myc). The pluripotency status of each induced PSC line was validated by comparison with human embryonic stem cells (ESCs). RESULTS: We found that OA patient-derived human synovial cells had human mesenchymal stem cell (MSC)-like characteristics, as indicated by the expression of specific markers, including CD14-, CD19-, CD34-, CD45-, CD44+, CD51+, CD90+, CD105+, and CD147+. Microarray analysis of human MSCs and human synovial cells further determined their unique and overlapping gene expression patterns. The pluripotency of established human induced PSCs was confirmed by their human ESC-like morphology, expression of pluripotency markers, gene expression profiles, epigenetic status, normal karyotype, and in vitro and in vivo differentiation potential. The potential of human induced PSCs to differentiate into distinct mesenchymal cell lineages, such as osteoblasts, adipocytes, and chondrocytes, was further confirmed by positive expression of markers for respective cell types and positive staining with alizarin red S (osteoblasts), oil red O (adipocytes), or Alcian blue (chondrocytes). Functional chondrocyte differentiation of induced PSCs in pellet culture and 3-dimensional polycaprolactone scaffold culture was assessed by chondrocyte self-assembly and histology. CONCLUSION: Our findings indicate that patient-derived synovial cells are an attractive source of MSCs as well as induced PSCs and have the potential to advance cartilage tissue engineering and cell-based models of cartilage defects.