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Chondrogenic differentiation of induced pluripotent stem cells from osteoarthritic chondrocytes in alginate matrix.

Abstract

Induced pluripotent stem cells (iPSCs) have the potential to revolutionise cell therapy; however, it remains unclear whether iPSCs can be generated from human osteoarthritic chondrocytes (OCs) and subsequently induced to differentiate into chondrocytes. In the present study, we investigated the differentiation potential of OCs into iPSCs using defined transcription factors and explored the possibility of using these OC-derived iPSCs for chondrogenesis. Our study demonstrates that iPSCs can be generated from OCs and that these iPSCs are indistinguishable from human embryonic stem cells (hESCs). To promote chondrogenic differentiation, we used lentivirus to transduce iPSCs seeded in alginate matrix with transforming growth factor-β1 (TGF-β1) and then in vitro co-cultured these iPSCs with chondrocytes. Gene expression analysis showed that this combinational strategy promotes the differentiation of the established iPSCs into chondrocytes in alginate matrix. Increased expression of cartilage-related genes, including collagen II, aggrecan, and cartilage oligomeric matrix protein (COMP), and decreased gene expression of the degenerative cartilage marker, vascular endothelial growth factor (VEGF), were observed. The histological results revealed a dense sulphated extracellular matrix in the co-culture of TGF-β1-transfected iPSCs with chondrocytes in alginate matrix. Additionally, in vivo chondroinductive activity was also evaluated. Histological examination revealed that more new cartilage was formed in the co-culture of TGF-β1-transfected iPSCs with chondrocytes in alginate matrix. Taken together, our data indicate that iPSCs can be generated from OCs by defined factors and the combinational strategy results in significantly improved chondrogenesis of OC-derived iPSCs. This work adds to our understanding of potential solutions to osteoarthritic cell replacement problem.

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  • Authors

    Wei Y, Zeng W, Wan R, Wang J, Zhou Q, Qiu S, Singh SR

    Source

    European cells & materials 23: 2012 pg 1-12

    MeSH

    Aggrecans
    Alginates
    Cartilage
    Cartilage Oligomeric Matrix Protein
    Cell Differentiation
    Cells, Cultured
    Chondrocytes
    Chondrogenesis
    Coculture Techniques
    Collagen Type II
    Extracellular Matrix
    Extracellular Matrix Proteins
    Gene Expression
    Glucuronic Acid
    Glycoproteins
    Hexuronic Acids
    Humans
    Induced Pluripotent Stem Cells
    Matrilin Proteins
    Osteoarthritis
    Transfection
    Transforming Growth Factor beta1
    Vascular Endothelial Growth Factor A

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22241609