The Multiparametric Effects of Hydrodynamic Environments on Stem Cell Culture

Abstract

Stem cells possess the unique capacity to differentiate into many clinically relevant somatic cell types, making them a promising cell source for tissue engineering applications and regenerative medicine therapies. However, in order for the therapeutic promise of stem cells to be fully realized, scalable approaches to efficiently direct differentiation must be developed. Traditionally, suspension culture systems are employed for the scale-up manufacturing of biologics via bioprocessing systems that heavily rely upon various types of bioreactors. However, in contrast to conventional bench-scale static cultures, large-scale suspension cultures impart complex hydrodynamic forces on cells and aggregates due to fluid mixing conditions. Stem cells are exquisitely sensitive to environmental perturbations, thus motivating the need for a more systematic understanding of the effects of hydrodynamic environments on stem cell expansion and differentiation. This article discusses the interdependent relationships between stem cell aggregation, metabolism, and phenotype in the context of hydrodynamic culture environments. Ultimately, an improved understanding of the multifactorial response of stem cells to mixed culture conditions will enable the design of bioreactors and bioprocessing systems for scalable directed differentiation approaches.

Differential Expression of Extracellular Matrix and Growth Factors by Embryoid Bodies in Hydrodynamic and Static Cultures

“…However, hydrodynamic cultures expose PSCs to complex physical and chemical environments consisting of spatially and temporally modulated fluid shear stresses and heterogeneous mass transport, 24 which could influence cell differentiation. Hydrodynamic culture systems…”

Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

“…129,130 Evidences were provided that the bioreactors enhanced oxygen and nutrient diffusion inside aggregates (100-300 mm) compared to static cultures. 131,132 The dynamic culture conditions create different oxygen profiles in MSC aggregates, which may affect the cell metabolism and phenotype. Control of oxygen tension inside bioreactors has been shown to induce biological signaling to modulate MSC fate decision.…”

Dendritic cells derived from pluripotent stem cells: Potential of large scale production

“…Different from traditional static tissue culture vessels, hPSCs in bioreactors are exposed to dynamic physiochemical environments. Especially, the presence of shear stress affects not only cell growth and viability, but also the cell phenotype and lineage commitment [23,62] . Understanding the impact of hydrodynamic environment on hPSC differentiation is a critical step to scale up the process for producing DCs from hPSCs.…”

“…Bioreactors for hPSC-derived cells Dynamic bioreactors can be used to enhance mass transfer coefficient, alter the kinetics of receptor-ligand binding, and control the aggregate collision [21,62,63] . Thus, stem cell aggregation, metabolism, and cell phenotype can be modulated in the hydrodynamic environment of bioreactors.…”