Induced Pluripotent Stem Cell-Differentiated Chondrocytes Repair Cartilage Defect in a Rabbit Osteoarthritis Model

Abstract

The aim of this study was to explore the therapeutic effect of iPSC-mesenchymal stem cell (MSC)-derived chondrocytes in a rabbit osteoarthritis (OA) model. The iPSCs were characterized by gene expressions, immunostaining of pluripotent markers, and in vivo teratoma formation. iPSC-differentiated MSCs were characterized by flow cytometry and trilineage differentiation. A rabbit OA model was established by the transection of the anterior cruciate ligament. The therapeutic effect of transplanted iPSC-MSC-chondrocytes on the OA was evaluated by the histology, immunostaining, and qPCR of defective cartilage. The results showed iPSC could express pluripotency markers such as OCT4, SOX2, and NANOG and form an embryoid body and a teratoma. After differentiation of iPSCs for 30 days, MSCs were established. The iPSC-MSC could express typical MSC markers such as CD29, CD44, CD90, CD105, and HLA-ABC. They could differentiate into adipocytes, osteocytes, and chondrocytes. In this model, iPSC-MSC-chondrocytes significantly improved the histology and ICRS (International Cartilage Repair Society) scores. The transplanted cartilage expressed less IL-1β, TNF-α, and MMP13 than control cartilage. In conclusion, the iPSCs we derived might represent an emerging source for differentiated MSC-chondrocyte and might rescue cartilage defects through its anti-inflammatory and anti-catabolic effects.

Mesenchymal stromal cell-based therapy for cartilage regeneration in knee osteoarthritis

“…Some researchers found decreased expressions of inflammatory and catabolic markers including IL-1β, TNF-α, and MMP13, after AT-MSCs injection [ 104 ], BM-MSCs injection [ 105 ], or induced pluripotent stromal cell-chondrocytes transplant in KOA model. However, no difference in Col-II and Col-I expression was found between transplanted cartilage and other groups [ 106 ]. One study determined that both IL-1β and TNF-α immunostaining in chondrocytes in the cartilage were significantly enhanced after human umbilical cord-derived MSCs treatment and reserved almost back to normal tissue.…”

Recent Advances in Extracellular Vesicle-Based Therapies Using Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells

“…The gene expression profiles of primary MSCs and iMSCs are very similar, but iMSCs show reduced capacity in suppressing T cell proliferation, suggesting a lower immunomodulatory property [ 27 ]. Nevertheless, age-related DNA methylation that was accumulated during in vitro culture was overall reset in iMSCs [ 29 , 30 ], consistent with a stronger regeneration ability of iMSCs in animal disease models and higher proliferation rates when compared to primary MSCs [ 31 , 32 , 33 , 34 ].…”

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

“…A similar observation was noted in the Chang team, which analysed iChondrocytes obtained in comparable conditions in a rabbit model. The researchers demonstrated that the differentiated chondrocytes effectively repaired cartilage defects in vivo and indicated a downregulation of catabolic and proinflammatory cytokines [120]. The possible explanations for this phenomenon were related to the rejuvenation of cells during differentiation and, also, the confirmation of their MSC nature, which is known for its suppressive and protective properties [88].…”