Osteoarthritis (OA) is a degenerative and chronic joint disease characterized by clinical symptoms and distortion of joint tissues. It primarily damages joint cartilage, causing pain, swelling, and stiffness around the joint. It is the major cause of disability and pain. The prevalence of OA is expected to increase gradually with the aging population and increasing prevalence of obesity. Many potential therapeutic advances have been made in recent years due to the improved understanding of the underlying mechanisms, diagnosis, and management of OA. Embryonic stem cells and induced pluripotent stem cells differentiate into chondrocytes or mesenchymal stem cells (MSCs) and can be used as a source of injectable treatments in the OA joint cavity. MSCs are known to be the most studied cell therapy products in cell-based OA therapy owing to their ability to differentiate into chondrocytes and their immunomodulatory properties. They have the potential to improve cartilage recovery and ultimately restore healthy joints. However, despite currently available therapies and advances in research, unfulfilled medical needs persist for OA treatment. In this review, we focused on the contents of non-cellular and cellular therapies for OA, and briefly summarized the results of clinical trials for cell-based OA therapy to lay a solid application basis for clinical research.

Skin is an organ that plays an important role as a physical barrier and has many other complex functions. Skin mimetics may be useful for studying the pathophysiology of diseases in vitro and for repairing lesions in vivo. Cord blood mononuclear cells (CBMCs) have emerged as a potential cell source for regenerative medicine. Human induced pluripotent stem cells (iPSCs) derived from CBMCs have great potential for allogenic regenerative medicine. Further study is needed on skin differentiation using CBMC-iPSCs. Human iPSCs were generated from CBMCs by Sendai virus. CBMC-iPSCs were differentiated to fibroblasts and keratinocytes using embryonic body formation. To generate CBMC-iPSC-derived 3D skin organoid, CBMC-iPSC-derived fibroblasts were added into the insert of a Transwell plate and CBMC-iPSC-derived keratinocytes were seeded onto the fibroblast layer. Transplantation of 3D skin organoid was performed by the tie-over dressing method. Epidermal and dermal layers were developed using keratinocytes and fibroblasts differentiated from cord blood-derived human iPSCs, respectively. A complex 3D skin organoid was generated by overlaying the epidermal layer onto the dermal layer. A humanized skin model was generated by transplanting this human skin organoid into SCID mice and effectively healed skin lesions. This study reveals that a human skin organoid generated using CBMC iPSCs is a novel tool for in-vitro and in-vivo dermatologic research.

Human degenerative cartilage has low regenerative potential. Chondrocyte transplantation offers a promising strategy for cartilage treatment and regeneration. Currently, chondrogenesis using human pluripotent stem cells (hiPSCs) is accomplished using human recombinant growth factors. Here, we differentiate hiPSCs into chondrogenic pellets using minicircle vectors. Minicircles are a non-viral gene delivery system that can produce growth factors without integration into the host genome. We generated minicircle vectors containing bone morphogenetic protein 2 (BMP2) and transforming growth factor beta 3 (TGFβ3) and delivered them to mesenchymal stem cell-like, hiPSC-derived outgrowth (OG) cells. Cell pellets generated using minicircle-transfected OG cells successfully differentiated into the chondrogenic lineage. The implanted minicircle-based chondrogenic pellets recovered the osteochondral defects in rat models. This work is a proof-of-concept study that describes the potential application of minicircle vectors in cartilage regeneration using hiPSCs.

Methotrexate (MTX) is widely used for the treatment of rheumatoid arthritis (RA). The drug is cost-effective, but sometimes causes hepatotoxicity, requiring a physician’s attention. In this study, we simulated hepatotoxicity by treating hepatocytes derived from RA patient–derived induced pluripotent stem cells (RA-iPSCs) with MTX. RA-iPSCs and healthy control iPSCs (HC-iPSCs) were established successfully. RA-iPSCs were differentiated into hepatocytes in two-dimensional (2D) monolayers and three-dimensional (3D) hepatocyte spheroid cultures; this process required growth factors such as BMP4, bFGF, HGF, and OSM. Immunofluorescence staining and flow cytometry were performed to confirm that the mature hepatocytes expressed cytokeratin 18, anti–alpha-1 antitrypsin, and albumin. MTX toxicity was evaluated via monitoring of cell viability, alanine aminotransferase, and mitochondrial status after MTX treatment in 2D and 3D cultures. RA-iPSCs generated from three RA patients suffering from MTX-induced hepatotoxicity differentiated into the endoderm lineage, hepatoblasts, and hepatocytes. In 2D culture, RA-iPSC-derived hepatocytes were more sensitive to MTX than healthy controls. A 3D culture system using hepatocyte spheroids also successfully recapitulated MTX-induced hepatotoxicity. The 3D culture system had several advantages, including longer culture periods under more complex conditions. A patient-derived iPSC platform could recapitulate MTX toxicity. Simulation of drug toxicity in vitro may help clinicians choose safer drugs or less toxic doses.

The BCH codes are widely used as Error Correcting Code (ECC) schemes for NAND Flash Memories. There have been strong demands to implement NAND Flash controller having low cost, low power and high throughput. We focus on BCH implementation since it has the largest portion in the controller. In this paper, we configure the 3-stage pipelined BCH decoder: syndrome computation, Berlekamp-Massey algorithm and Chien search. We implement BCH decoder supporting 800MB/s using the pipelined structure and the early termination method.

Early osteoarthritis (OA)-like symptoms are difficult to study owing to the lack of disease samples and animal models. In this study, we generated induced pluripotent stem cell (iPSC) lines from a patient with a radiographic early-onset finger osteoarthritis (efOA)-like condition in the distal interphalangeal joint and her healthy sibling. We differentiated those cells with similar genetic backgrounds into chondrogenic pellets (CPs) to confirm efOA. CPs generated from efOA-hiPSCs (efOA-CPs) showed lower levels of COL2A1, which is a key marker of hyaline cartilage after complete differentiation, for 21 days. Increase in pellet size and vacuole-like morphologies within the pellets were observed in the efOA-CPs. To analyze the changes occurred during the development of vacuole-like morphology and the increase in pellet size in efOA-CPs, we analyzed the expression of OA-related markers on day 7 of differentiation and showed an increase in the levels of COL1A1, RUNX2, VEGFA, and AQP1 in efOA-CPs. IL-6, MMP1, and MMP10 levels were also increased in the efOA-CPs. Taken together, we present proof-of-concept regarding disease modeling of a unique patient who showed OA-like symptoms.