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New research presented on June 16, 2011 at the annual meeting of the International Society for Stem Cell Research (ISSCR) shows that systematically controlling the local and global environments during stem cell development helps to effectively direct the process of differentiation. In the future, these findings could be used to develop manufacturing procedures for producing large quantities of stem cells for diagnostic and therapeutic applications. The research is sponsored by the National Science Foundation and the National Institutes of Health.

“We have developed several platforms that will allow us to conduct head-to-head studies with different kinds of stem cells to determine if one type of stem cell outperforms another type for a certain application,” said McDevitt, who is also a Petit Faculty Fellow in the Institute for Bioengineering and Bioscience at Georgia.

Many laboratory growth methods allow stem cells to aggregate in three-dimensional clumps called “embryoid bodies” during differentiation. McDevitt and biomedical engineering graduate student Andres Bratt-Leal incorporated biomaterial particles directly within these aggregates during their formation. They introduced microparticles made of gelatin, poly(lactic-co-glycolic acid) (PLGA) or agarose and tested their impact on the assembly, intercellular communication and morphogenesis of the stem cell aggregates under different conditions by varying the microsphere-to-cell ratio and the size of the microspheres.

The researchers found that the presence of the biomaterials alone modulated embryoid body differentiation, but did not adversely affect cell viability. Compared to typical delivery methods, providing differentiation factors — retinoic acid, bone morphogenetic protein 4 (BMP4) and vascular endothelial growth factor (VEGF) — via microparticles induced changes in the gene and protein expression patterns of the aggregates.

While microparticles can be used to control differentiation by regulating the local environment, other methods exist to control differentiation through the global environment. Experiments by McDevitt and biomedical engineering graduate student Melissa Kinney have demonstrated that modulating hydrodynamic conditions can dictate the morphology of cell aggregate formation and control the expression of differentiated phenotypic cell markers.

“Because bioreactors typically impose hydrodynamic forces on cells to cultivate large volumes of cells at high density, our use of hydrodynamics to control cell fate decisions represents a novel, yet simple, principle that could be used in the future for the scalable efficient production of stem cells,” added McDevitt.

Technologies capable of being directly integrated into bioprocessing systems will be the best choice for manufacturing large batches of stem cells, he noted. In the future, the development of multi-scale techniques that combine different levels of control — both local and global — to regulate stem cell differentiation may help the translation of stem cells into viable clinical therapies.

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