AI Article Synopsis

  • Mesenchymal stem cells (MSCs) show promise for regenerative medicine, but their clinical use requires consistent preparation methods to prevent unintended differentiation due to various environmental factors.
  • This study examined how different levels of hydrodynamic loading affect the differentiation of MSCs into bone and cartilage lineages when supplemented with factors like TGF-β3 and BMP-2 under static and dynamic conditions.
  • Results indicated that while hydrodynamic loading alone had limited impact, it enhanced gene expression for bone and cartilage formation when combined with the inductive factors, particularly at high shear rates; however, care must be taken to avoid unwanted osteogenic differentiation in chondrogenic cultures.

Article Abstract

Background: Mesenchymal stem cells (MSCs) are viewed as a having significant potential for tissue engineering and regenerative medicine therapies. Clinical implementation of MSCs, however, demands that their preparation be stable and reproducible. Given that environmental and bioprocessing parameters such as substrate stiffness, seeding densities, culture medium composition, and mechanical loading can result in undirected differentiation of the MSC population, the objective of this study was to systematically investigate how hydrodynamic loading influences the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) towards the osteochondral lineages both in the presence and absence of exogenous, inductive factors.

Methods: Expanded bovine MSCs were suspended in 2.5 % agarose, cast in a custom mold, and placed into either static or one of two dynamic culture environments consisting of "high" and "low" magnitude shear conditions. Constructs were supplemented with varying concentrations (0, 1, 10, 100 ng/mL) of either TGF-β3 or BMP-2 throughout cultivation with tissue samples being collected following each week of culture.

Results: In the absence of exogenous supplementation, hydrodynamic loading had little effect on cell phenotype at either magnitude of stimulation. When cultures were supplemented with BMP-2 and TGF-β3, MSCs gene expression progressed towards the osteogenic and chondrogenic pathways, respectively. This progression was enhanced by the presence of hydrodynamic loading, particularly under high shear conditions, but may point the chondrogenic cultures down a hypertrophic path toward osteogenesis reminiscent of endochondral ossification if TGF-β3 supplementation is insufficient.

Conclusions: Moving forward, these results suggest bioprocessing conditions which minimize exposure of chondrogenic cultures to fluid shear stress to avoid undesirable differentiation of the MSC population.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736240PMC
http://dx.doi.org/10.1186/s12896-016-0240-6DOI Listing

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