Abstract
BackgroundOrganogenesis from tonsil-derived mesenchymal cells (TMSCs) has been reported, wherein tenogenic markers are expressed depending on the chemical stimulation during tenogenesis. However, there are insufficient studies on the mechanical strain stimulation for tenogenic cell differentiation of TMSCs, although these cells possess advantages as a cell source for generating tendinous tissue. The purpose of this study was to investigate the effects of mechanical strain and transforming growth factor-beta 3 (TGF-β3) on the tenogenic differentiation of TMSCs and evaluate the expression of tendon-related genes and extracellular matrix (ECM) components, such as collagen.ResultsmRNA expression of tenogenic genes was significantly higher when the mechanical strain was applied than under static conditions. Moreover, mRNA expression of tenogenic genes was significantly higher with TGF-β3 treatment than without. mRNA expression of osteogenic and chondrogenic genes was not significantly different among different mechanical strain intensities. In cells without TGF-β3 treatment, double-stranded DNA concentration decreased, while the amount of normalized collagen increased as the intensity of mechanical strain increased.ConclusionsMechanical strain and TGF-β3 have significant effects on TMSC differentiation into tenocytes. Mechanical strain stimulates the differentiation of TMSCs, particularly into tenocytes, and cell differentiation, rather than proliferation. However, a combination of these two did not have a synergistic effect on differentiation. In other words, mechanical loading did not stimulate the differentiation of TMSCs with TGF-β3 supplementation. The effect of mechanical loading with TGF-β3 treatment on TMSC differentiation can be manipulated according to the differentiation stage of TMSCs. Moreover, TMSCs have the potential to be used for cell banking, and compared to other mesenchymal stem cells, they can be procured from patients via less invasive procedures.
Highlights
Organogenesis from tonsil-derived mesenchymal cells (TMSCs) has been reported, wherein tenogenic markers are expressed depending on the chemical stimulation during tenogenesis
Transforming growth factor-beta 3 (TGF-β3) decreased the mRNA expression of SCX (p = 0.001; Fig.1A) and collagen type 1 (COL1) (p < 0.001; Fig.2A) on day 14 as well as that of Collagen type 3 (COL3) on days 7 and 14 (p < 0.001; Fig.2B)
COL3 expression was decreased in the 2% strain group on day 3(p = 0.043; Fig.2B), and there was no statistically significant difference in the COL1/3 ratio between the strain groups without TGF-β3 (Fig.2C)
Summary
Organogenesis from tonsil-derived mesenchymal cells (TMSCs) has been reported, wherein tenogenic markers are expressed depending on the chemical stimulation during tenogenesis. Direct repair or tendon transfer is predominantly used to treat tendinopathy [4, 5] These remedies have some disadvantages as follows: the repair site consists of fibrous tissue rather than the original tissue post-surgery, which may cause fibrosis; the healing potency is low to eliminate scarring; and adhesion with other connective tissues is low [6]. To overcome these drawbacks, mesenchymal stem cells (MSCs) have been developed for use in tissue engineering. MSCs have shown promising potential for tendon repair in vitro and in animal studies [8, 9]
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