Hydrodynamic modulation of pluripotent stem cells

Abstract

Controlled expansion and differentiation of pluripotent stem cells (PSCs) using reproducible, high-throughput methods could accelerate stem cell research for clinical therapies. Hydrodynamic culture systems for PSCs are increasingly being used for high-throughput studies and scale-up purposes; however, hydrodynamic cultures expose PSCs to complex physical and chemical environments that include spatially and temporally modulated fluid shear stresses and heterogeneous mass transport. Furthermore, the effects of fluid flow on PSCs cannot easily be attributed to any single environmental parameter since the cellular processes regulating self-renewal and differentiation are interconnected and the complex physical and chemical parameters associated with fluid flow are thus difficult to independently isolate. Regardless of the challenges posed by characterizing fluid dynamic properties, hydrodynamic culture systems offer several advantages over traditional static culture, including increased mass transfer and reduced cell handling. This article discusses the challenges and opportunities of hydrodynamic culture environments for the expansion and differentiation of PSCs in microfluidic systems and larger-volume suspension bioreactors. Ultimately, an improved understanding of the effects of hydrodynamics on the self-renewal and differentiation of PSCs could yield improved bioprocessing technologies to attain scalable PSC culture strategies that will probably be requisite for the development of therapeutic and diagnostic applications.

Figure 1

Comparison of hydrodynamic culture systems for pluripotent stem cell culture. Microfluidic devices provide a scale-down approach to examining hydrodynamic effects on pluripotent stem cells with precise spatial and temporal control and high-throughput formats. At the other end of the spectrum, bioreactors can be scaled up utilizing hydrodynamic systems with more complex and heterogeneous flow environments. 2D, two-dimensional; 3D, three-dimensional.

Figure 2

Utility of hydrodynamics in pluripotent stem cell research. Although the physical and chemical effects on pluripotent stem cells can be difficult to isolate, cell signaling and mechanotransduction can be examined by modulating the hydrodynamic flow in culture systems. Understanding the effects of hydrodynamics on pluripotent biology can be increased with high-throughput screening and will facilitate the development of a biomanufacturing in scalable bioreactor systems.