Tendon-Derived Extracellular Matrix Enhances Transforming Growth Factor-β3-Induced Tenogenic Differentiation of Human Adipose-Derived Stem Cells

Abstract

Because of the limited and unsatisfactory outcomes of clinical tendon repair, tissue engineering approaches using adult mesenchymal stem cells are being considered a promising alternative strategy to heal tendon injuries. Successful and functional tendon tissue engineering depends on harnessing the biochemical cues presented by the native tendon extracellular matrix (ECM) and the embedded tissue-specific biofactors. In this study, we have prepared and characterized the biological activities of a soluble extract of decellularized tendon ECM (tECM) on adult adipose-derived stem cells (ASCs), on the basis of histological, biochemical, and gene expression analyses. The results showed that tECM enhances the proliferation and transforming growth factor (TGF)-b3-induced tenogenesis of ASCs in both plate and scaffold cultures in vitro, and modulates matrix deposition of ASCs seeded in scaffolds. These findings suggest that combining tendon ECM extract with TGFb3 treatment is a possible alternative approach to induce tenogenesis for ASCs.

Mechanisms of Action of Multipotent Mesenchymal Stromal Cells in Tendon Disease

“…Growth factors used for induction of tenogenic differentiation mainly include transforming growth factor-β family members (TGF-β [47,51,53,60,66,86,88] [49]. A promising stepwise differentiation approach has also been reported using TGF-β1 followed by connective tissue growth factor (CTGF) [54].…”

Biologics and stem cell‐based therapies for rotator cuff repair

“…One strategy for stem cell‐based rotator cuff repair harnesses their multipotent capacity to direct differentiation toward a tendon or fibrocartilage phenotype. Differentiation can be carried out in vitro to create an engineered tendon/enthesis construct prior to implantation, or naive MSCs can be delivered within a biomimetic matrix to promote the proper cell fate in situ . Commonly used scaffolds for rotator cuff include electrospun fibers, xenograft tendon scaffolds, or hydrogels (typically fibrin or type I collagen gels) .…”

“…Differentiation can be carried out in vitro to create an engineered tendon/enthesis construct prior to implantation, or naive MSCs can be delivered within a biomimetic matrix to promote the proper cell fate in situ. [116][117][118][119] Commonly used scaffolds for rotator cuff include electrospun fibers, xenograft tendon scaffolds, or hydrogels (typically fibrin or type I collagen gels). 43,59,[120][121][122][123] The use of a carrier vehicle is advantageous since it ensures proper localization of delivered cells; the environment provided by the scaffolds has the additional potential to improve host cell proliferation or differentiation.…”

Do There Exist Innovative Perspectives in Tissue Engineering-Based Ligament Reconstruction?

“…8,9 In addition, the ECMs promote differentiation of precursor cells. 10,11 Scaffolds for ligament tissue engineering can be produced by various techniques such as braiding, embroidering, 3D printing, electrospinning, electro hydrodynamic jet printing and combinations of them. 6,10,[12][13][14][15] Aligned, interwoven and multilayered composite structures most likely reflect the natural aligned ligament ultrastructure and biomechanics.…”

“…The presence of stimulatory GFs or natural ligament ECM is especially advantageous if precursor cells are used to produce a tissue engineered neotendon or-ligament. 11 Multipotent stromal cells (MSCs) are highly attractive for musculoskeletal tissue reconstruction due to their favorable properties such as high proliferative capacity, plasticity, differentiation potential, low immunogenicity, immunomodulatory capacity, trophic effects and higher availability. 22 Harvesting MSCs presents lower donor site morbidity than harvesting primary tissue-specific resident cells such as ligamentocytes.…”