The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332-0532, USA.
Tissue Eng Part B Rev. 2011 Aug;17(4):249-62. doi: 10.1089/ten.TEB.2011.0040. Epub 2011 May 25.
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.
干细胞具有分化为许多临床相关体细胞类型的独特能力，使其成为组织工程应用和再生医学疗法有前途的细胞来源。然而，为了充分实现干细胞的治疗潜力，必须开发出可扩展的方法来有效地指导分化。传统上，通过严重依赖各种类型生物反应器的生物加工系统，采用悬浮培养系统来扩大生物制剂的规模生产。然而，与传统的台式静态培养相比，由于流体混合条件，大规模悬浮培养对细胞和聚集体施加复杂的流体动力。干细胞对环境干扰非常敏感，因此需要更系统地了解流体动力环境对干细胞扩增和分化的影响。本文讨论了在流体动力学培养环境中干细胞聚集、代谢和表型之间的相互依存关系。最终，对干细胞对混合培养条件的多因素反应的深入了解将能够设计用于可扩展定向分化方法的生物反应器和生物加工系统。
