Viabilité et fonctionnalité des cellles souches mésenchymateuses humaines dans un environnement ischémique

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

The Regenerative Potential of Notochordal Cells in a Nucleus Pulposus Explant

International audienc

Directing bone marrow-derived stromal cell function with mechanics

Because bone marrow-derived stromal cells (BMSCs) are able to generate many cell types, they are envisioned as source of regenerative cells to repair numerous tissues, including bone, cartilage, and ligaments. Success of BMSC-based therapies, however, relies on a number of methodological improvements, among which better understanding and control of the BMSC differentiation pathways. Since many years, the biochemical environment is known to govern BMSC differentiation, but more recent evidences show that the biomechanical environment is also directing cell functions. Using in vitro systems that aim to reproduce selected components of the in vivo mechanical environment, it was demonstrated that mechanical loadings can affect BMSC proliferation and improve the osteogenic, chondrogenic, or myogenic phenotype of BMSCs. These effects, however, seem to be modulated by parameters other than mechanics, such as substrate nature or soluble biochemical environment. This paper reviews and discusses recent experimental data showing that despite some knowledge limitation, mechanical stimulation already constitutes an additional and efficient tool to drive BMSC differentiation.Peer Reviewe

Influencing biophysical properties of fibrin with buffer solutions

Fibrin has been proposed as cell scaffold for numerous tissue engineering applications. While most of the studies have focused on fibrinogen and thrombin, other components of fibrin can also affect its properties. The present study aimed to evaluate the effects of buffer solu- tion composition on fibrin biophysical properties. Fibrin scaffolds were synthesized with different calcium, chlo- ride, and factor XIII (FXIII) final concentrations. Light transmission was determined as a relative, semi-quantita- tive estimator of fiber structure differences, and two com- positions, resulting in translucent and opaque gels, were tested for mechanical and biological properties. Gels were seeded with mouse mesenchymal cells, C3H10T1/2, or bovine bone marrow-derived mesenchymal stromal cells and cultured up to 10 or 24 days, before cell number, morphology and distribution were evaluated. Calcium increased gel opacity (i.e., fiber thickness), while chloride and FXIII decreased it. Opaque gels displayed a fluid-like viscous behavior while translucent gels showed improved elastic properties. Both compositions supported survival of both cell types with opaque gels leading to better prolif- eration, but significant scaffold shrinkage after 17 days of culture. These results demonstrated that calcium, chloride, and FXIII modulate the biophysical properties of fibrin, and can be used to adjust mechanical and biological properties for tissue engineering applicationsPeer ReviewedPostprint (published version

Culturing bovine nucleus pulposus explants by balancing medium osmolarity

Regenerative therapies are promising treatments for early intervertebral disc degeneration. To test their efficacy, an in vitro tissue-level model would be valuable. Nucleus pulposus (NP) explant culture may constitute such a model, as the earliest signs of degeneration are in the NP. However, in NP explant cultures, balancing tissue osmolarity is crucial to preventing swelling, proteoglycan (PG) loss and, therefore, maintaining a native cell environment. In this study, we investigated the effect of medium osmolarity on NP explants. We hypothesized that balancing the inherent tissue osmolarity would prevent swelling and thus maintain NP tissue in a native state. Bovine NP explants were cultured for 21 days in hypo-, iso-, and hyper-tonic conditions using either sucrose or polyethylene glycol (PEG) to raise medium osmolarity. Explants were analyzed for water and biochemical content, cell viability, gene expression, and tissue histology, and compared to day 0 samples. In hypo-tonic and both sucrose cultures, swelling was not prevented, resulting in PG loss and changes in cell behavior. Only PEG cultures maintained water and biochemical content and a histological aspect similar to those of native tissue, with better results for hyper- than for iso-tonic conditions. Using PEG to raise culture medium osmolarity, we were able to maintain the NP tissue specific matrix composition, important for disc cell behavior. This approach, thus, constitutes a promising model to test regenerative therapies for early intervertebral disc degeneration