IGF-1 Gene Transfer to Human Synovial MSCs Promotes Their Chondrogenic Differentiation Potential without Induction of the Hypertrophic Phenotype

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.

Mesenchymal stem cells for cartilage regeneration

“…41 The transfection of the IGF gene into MSCs promoted the chondrogenic differentiation potential without the induction of hypertrophic phenotype. 42 The content of GAG and the expression of Col IIA1 were improved in the IGF-MSC group, and IGF-induced tissue showed a similar prosperity with the chondrocyte phenotype.…”

Incorporating insulin growth Factor‐1 into regenerative and personalised medicine for musculoskeletal disorders: A systematic review

“…The factors involved in cartilage regeneration include the cell migration to the site of injury, proliferation, expression of chondrogenic markers, production of bioactive peptides responsible for chondrogenic regeneration and differentiation into chondrogenic cell lineages (Armakolas et al, 2016, pp. 3066-3072;Clark et al, 2014;Garza-Veloz et al, 2013;Ikeda et al, 2017;Pasold et al, 2015;Tiwary et al, 2014;Zhao et al, 2014Zhao et al, , 2019.…”

Pathomechanisms of Posttraumatic Osteoarthritis: Chondrocyte Behavior and Fate in a Precarious Environment

“…The latter pathway is predominantly associated with aging and OA, resulting from a strong decrease of TGF-ß receptor ALK5 and subsequent shift in the ALK1/ALK5 ratio [59]. In contrast to other growths factors, BMP7 as well as insulin-like growth factor-1 (IGF-1) contribute to the maintenance of the chondrogenic phenotype without inducing hypertrophic processes [60,61].…”