Characterization of Early-Onset Finger Osteoarthritis-Like Condition Using Patient-Derived Induced Pluripotent Stem Cells

Abstract

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.

The Induced Pluripotent Stem Cells in Articular Cartilage Regeneration and Disease Modelling: Are We Ready for Their Clinical Use?

“…In addition to several types of skeletal dysplasia, a number of OA models have also been created, such as hand OA, early-onset finger OA, and chemically induced OA (stimulation of a formed osteochondral plug in a dual-flow bioreactor with IL-1β) [177][178][179]. The introduction mentioned that OA is a complex disease with several environmental and genetic background factors [12].…”

“…Both the Rims and Castro-Viñuelas teams' studies yielded similar data, showing the less chondrogenic potential of iPSC from OA patients than in healthy donors. It was assessed by the reduced expression of hyaline cartilage markers deposition of the ECM with a parallel increased expression of hypertrophic markers related to the late stages of chondrogenesis [177,178]. Lin et al carried out an interesting study, in which they created a construct that consisted of mesenchymal progenitor cells derived from iPSC cells suspended in methacrylate gelatin, which was used to create an osteochondral plug in the dual-flow bioreactor [179].…”

Application of Induced Pluripotent Stem Cells for Disease Modeling and 3D Model Construction: Focus on Osteoarthritis

“…Rim et al recently examined the genetic characteristics of iPSC-derived OA disease models [84]. Dermal fibroblasts were harvested from a patient with radiographic earlyonset finger osteoarthritis (efOA)-like condition and her healthy siblings.…”

“…Hence, hiPSCs were first placed in a 1:1 mixture of E8 media and Aggrewell media to form embryonic bodies (EBs). Subsequently, the outgrown cells (OGs) were induced with the EBs in the OG induction media and then placed together in chondrogenic differentiation media to form chondrogenic pellets [84,[89][90][91][92][93]. The two pellets (from efOA-like condition patient and healthy siblings) were maintained for 21 days to observe the osteochondral changes in the respective disease models.…”

Editorial for Special Issue: iPS Cells (iPSCs) for Modelling and Treatment of Human Diseases

“…In this Special Issue, we have collected articles that emphasise the wide application possibilities of iPSCs. The publications cover diseases of brain [ 2 , 3 , 4 , 5 ], kidney [ 6 ], blood [ 7 , 8 ], cartilage [ 9 ] and primordial germ cells [ 10 ] in 2D and 3D models.…”