Abstract
Mesenchymal Stem Cells (MSCs) and tissue-specific progenitors have been proposed as useful tools for regenerative medicine approaches in bone, cartilage and tendon-related pathologies. The differentiation of cells towards the desired, target tissue-specific lineage has demonstrated advantages in the application of cell therapies and tissue engineering. Unlike osteogenic and chondrogenic differentiation, there is no consensus on the best tenogenic induction protocol. Many growth factors have been proposed for this purpose, including BMP-12, b-FGF, TGF-β3, CTGF, IGF-1 and ascorbic acid (AA). In this study, different combinations of these growth factors have been tested in the context of a two-step differentiation protocol, in order to define their contribution to the induction and maintenance of tendon marker expression in adipose tissue and bone marrow derived MSCs and tendon cells (TCs), respectively. Our results demonstrate that TGF-β3 is the main inducer of scleraxis, an early expressed tendon marker, while at the same time inhibiting tendon markers normally expressed later, such as decorin. In contrast, we find that decorin is induced by BMP-12, b-FGF and AA. Our results provide new insights into the effect of different factors on the tenogenic induction of MSCs and TCs, highlighting the importance of differential timing in TGF-β3 stimulation.
Highlights
Tendon disorders are a complex class of pathologies affecting a significant percentage of the worldwide population [1,2]
After 3 days of tenogenic induction, the presence of decorin (DCN) and scleraxis (SCX) was assessed in cells cultured with different growth factor combinations (Table 1)
Bone Morphogenetic Protein-12 (BMP-12) was able to induce the expression of DCN in all cell types analyzed, which was visible in the form of red filaments when observed by fluorescence microscopy (Figure 1d–f)
Summary
Tendon disorders are a complex class of pathologies affecting a significant percentage of the worldwide population [1,2]. Different literature reports have described tenogenic induction protocols using Bone Morphogenetic Protein-12 (BMP-12) alone or combined with Connective Tissue Growth Factor (CTGF) and ascorbic acid (AA) [4,22,23,24,25,26]. These protocols often only resulted in an unsatisfactory increase of tenogenic marker expression. The tenogenic potential of MSCs from different origins was investigated in order to identify the most suitable cell source for future regenerative medicine-based treatments of tendon disorders
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