Enhancement of tenogenic differentiation of human adipose stem cells by tendon-derived extracellular matrix

Abstract

Mesenchymal stem cells (MSCs) have gained increasing research interest for their potential in improving healing and regeneration of injured tendon tissues. Developing functional three-dimensional (3D) scaffolds to promote MSC proliferation and differentiation is a critical requirement in tendon tissue engineering. Tendon extracellular matrix has been shown to maintain the tenogenic potential of tendon stem cells and stimulate tenogenesis of human adipose stem cells (hASCs) in 2D culture. This study aims at characterizing the biological composition of urea-extracted fraction of tendon ECM (tECM) and its tenogenic effect on hASCs cultured in a 3D collagen scaffold under uniaxial tension. The tECM obtained was cell-free and rich in ECM proteins. hASCs seeded in tECM supplemented scaffold exhibited significantly increased proliferation and tenogenic differentiation. The presence of tECM also greatly suppressed the osteogenic differentiation of hASCs triggered by uniaxial tension. In addition, tECM-supplemented constructs displayed enhanced mechanical strength, accompanied by reduced expression and activity of MMPs in the seeded hASCs, indicating a regulatory activity of tECM in cell-mediated scaffold remodeling. These findings support the utility of tECM in creating bio-functional scaffolds for tendon tissue engineering.

Harnessing magnetic-mechano actuation in regenerative medicine and tissue engineering

“…This can be achieved by labelling stem cells with superparamagnetic iron oxide nanoparticles (SPIONs) and applying a magnetic field to further guide their migration to sites requiring increased cell retention [70,71] (Figure 1D). Importantly, cell labelling with SPIONs appears not to affect viability, proliferation, or specification of MSCs into adipogenic, chondrogenic, or osteogenic lineages under in vivo conditions [72]. Similar findings were observed in magnetite-labelled neural stem cells [73].…”

“…These results, as well as the fact that uptake of SPIONs has no impact on viability or differentiation potential in a diverse array of cells [72,73], are good indicators of the safety of magnetically actuated materials. However, longterm in vivo tests must be undertaken before drawing further conclusions.…”

Aging of the skeletal muscle extracellular matrix drives a stem cell fibrogenic conversion

“…Muscle from young and old animals was equally divided and prepared in duplicate ( n  = 2 per age), and a water‐soluble fraction of muscle ECM was prepared as previously described (Yang et al ., 2013). Solubilized ECM extracts were used to coat the bottom of chamber slides at 50 μL per well.…”

Three-Dimensional Culture and Transforming Growth Factor Beta3 Synergistically Promote Tenogenic Differentiation of Equine Embryo-Derived Stem Cells

“…Three-dimensional constructs have also been utilized to manipulate and direct certain pathways of differentiation in stem cells, including those of tenocyte lineages from MSCs. These include growth under ''static tension'' (produced by anchoring the gel), 8,[12][13][14] ''uniaxial applied tension'' (an externally applied constant force), 15 ''cyclical tension'' (exposure to externally applied and released forces), 12,16 and seeding cells on electrochemically aligned collagen. 17 When cells are cultured in anchored gels, they are under tension in what has been described as a ''static'' culture system.…”