Abstract
Mesenchymal stem cell- (MSC-) based therapy is a promising treatment for cartilage. However, repair tissue in general fails to regenerate an original hyaline-like tissue. In this study, we focused on increasing the expression levels for insulin-like growth factor-1 (IGF-1) to improve repair tissue quality. The IGF-1 gene was introduced into human synovial MSCs with a lentiviral vector and examined the levels of gene expression and morphological status of MSCs under chondrogenic differentiation condition using pellet cultures. The size of the pellets derived from IGF-1-MSCs were significantly larger than those of the control group. The abundance of glycosaminoglycan (GAG) was also significantly higher in the IGF-1-MSC group. The histology of the IGF-1-induced pellets demonstrated similarities to hyaline cartilage without exhibiting features of a hypertrophic chondrocyte phenotype. Expression levels for the Col2A1 gene and protein were significantly higher in the IGF-1 pellets than in the control pellets, but expression levels for Col10, MMP-13, ALP, and Osterix were not higher. Thus, IGF-1 gene transfer to human synovial MSCs led to an improved chondrogenic differentiation capacity without the detectable induction of a hypertrophic or osteogenic phenotype.
Highlights
Articular cartilage (AC) has limited self-repair capabilities due in part to poor vascularity, no lymphatic system, and no innervation
Previous research has demonstrated that the size of the pellet cultures is a good assessment parameter to evaluate achievement of chondrogenesis using pellet-culture differentiation methods [33]
We measured the diameters of the pellet developed from the pLVSIN-insulin-like growth factor-1 (IGF-1)-transfected Mesenchymal stem cells (MSCs)
Summary
Articular cartilage (AC) has limited self-repair capabilities due in part to poor vascularity, no lymphatic system, and no innervation. Mesenchymal stem cells (MSCs) have the capability to differentiate into a variety of connective tissue cells including bone, cartilage, tendon, muscle, and adipose tissue [8]. These MSCs may be readily isolated from many sources such as the bone marrow, skeletal muscle, synovial membranes, adipose tissue, and umbilical cord blood [9,10,11,12,13,14,15,16]. MSCs isolated from synovial membrane may be well suited for cell-based therapies for cartilage repair because of the relative ease of their harvest and their strong capability for chondrogenic differentiation
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