Cell-based assays have expanded in use, and reduced in sample requirements over the past decade, driven by technologies that have improved the culture and monitoring of cell functions on a miniature scale. One of our partners, Microstem Inc., based in San Diego, CA, is an example of an early stage reagent development company that approached Grace Bio-Labs for technical solutions to supply their system for cell-based assays.The MicroMatrix(tm) system from Microstem consists of an array of various extracellular matrices printed onto a hydrogel-coated microscope slide. The system enables parallel culture of cells in the presence of hundreds to thousands of fully defined extracellular matrices in order to determine the precise cellular microenvironment that affects cell behavior and functions, including adhesion, proliferation and differentiation.
“The advantage of our system is the use of defined human matrices in a miniaturized platform, which allows researchers to study a variety of cellular microenvironments in parallel with high reproducibility. This platform is particularly useful when conducting studies using primary cells, such as stem cell and tumor cells” says Marie Zhang, COO at Microstem. “Many of the matrices provided by other vendors are derived from complex biological material which can vary from lot-to-lot and frequently is not xeno-free,” explains Marie. In addition to the defined matrices, MicroMatrix technology incorporates surface rigidity into the cellular microenvironment design. The hydrogel coating not only provides a tunable soft surface for cell growth, it also serves as an attachment point for printed extracellullar matrices. The fact that the cells are cultured directly on a microscope slide format makes this system highly compatible with many standard imaging systems for monitoring the cells.
Microstem came to Grace Bio-Labs to find a way to create micro-chambers on their slide format. The chambers needed to be bio-compatible, adhere to the hydrogel coated slide surface without leaking between chambers, and able to be sterilized. Our ProPlate(tm) and FlexWell(tm) systems provided round wells that were deep enough to provide appropriate volumes of culture media. Thus the expertise in extracellular matrix and cell culture from Microstem combined with the microfluidic manufacturing expertise of Grace Bio-Labs was an excellent match for product development.
Most of the product development ideas for Microstem come from internal expertise in bioengineering and cell biology. However, sometimes collaborations with customers evolve into new products. One recent collaboration for Microstem was with a customer wanting to develop a physiological relevant system for primary leukemia cell culture. “Leukemia is a highly diverse tumor and finding the right conditions for culturing primary leukemia cells remains challenging,” comments Marie. As a relatively small company, Microstem can be very nimble in incorporating custom formulations into their format, says Marie.
When asked about potential clinical applications for their technology, Marie points to primary tumor cell assays to test cancer drug sensitivity for personalized medicine. Culturing primary tumor cells requires creating diverse microenvironments similar to where cancer cells reside inside of the body. By providing a wide variety of matrices and combinations, researchers can rapidly and efficiently screen many different conditions with small amounts of cells using the MicroMatrix system. In the future, physicians will be able to test a patient’s own cancer tumor cells in vitro to select the appropriate drug for therapy. Welcome to the true challenge of personalized medicine: translating the predictive power of genetics to the practical application of biological relevance.
Brafman D., Shah KD, Fellner T, Chien S, Willert K. (2009) “Defining Long-Term Maintenance Conditions of Human Embryonic Stem Cells With Arrayed Cellular Microenvironment Technology.” Stem Cells Dev., 18(8): 1141-1154.
Brafman, D, de Minicis S, Seki E, Shah KD, Teng D, Brenner D, Willert K, Chien S. (2009) “Investigating the role of the extracellular environment in modulating hepatic stellate cell biology with arrayed combinatorial microenvironments”. Integr. Biol., 1(8): 513 – 524.