Cell Therapy Manufacturing: Harvest

View Our Article published through BioPharm International, a global magazine integrating the science and business of research, development and manufacturing: Harvest of Human Mesenchymal Stem Cells from Microcarriers, Schnitzler, et al., 2017, Harvest of Human


Large-scale industrialized production of human mesenchymal stem cells (hMSCs) is necessary to continue advancement through human clinical trials and commercialization as therapeutics. However, achieving this level of production while meeting rigorous quality standards will depend on further progress in the areas of cell culture and scale-up, characterization, enrichment, and purification to deliver a consistent and reproducible supply of cells.

Planar surfaces such as well plates and tissue culture flasks have been the mainstay expansion platform for adherent cells when handling low to moderate cell quantities.  As previously reviewed by the authors (1), when larger cell yields are required, multilayer flasks, spinner flasks, and bioreactors are higher-capacity options. Though multilayer flasks may be scaled to meet moderate yield needs, they remain laborious to handle and can encumber the ability to effectively monitor cell health or marker status during cultivation. Alternatively, microcarrier-based systems allow for higher cell density cultures and enable in-process sample collection for off-line cell characterization. Furthermore, the bioreactor system precisely controls culture parameters such as pH and dissolved oxygen levels, as well as nutrient management through feed additions.

Following expansion, cells must be efficiently removed and separated from the growth surface, a process that is increasingly complex when moving from planar to microcarrier-based bioreactor cultures with large working volumes. In this article, the authors discuss approaches for optimizing conditions for the detachment of hMSCs from microcarriers and highlight a simple device for the retention of microcarriers and recovery of cells.

From this paper, you will learn about:

  • Effective methods for high recovery of hMSCs from microcarriers
  • Concentration strategies for rTrypsin and trypsin-specific inhibitors that are animal-origin free
  • Stirred-tank bioreactor systems that enable closed, controlled downstream processing


As cell-based therapeutics progress through clinical testing, there will be an increased need for scalable cell-manufacturing technologies that use non-animal-derived materials and are compatible with a limited number of downstream processing steps. Bioreactor-based manufacturing processes for hMSCs can drive higher cell yields per volume and unit operation, yet also introduce the requirement to separate cells from microcarriers. The incorporation of appropriately sized woven mesh filters or membrane filters into a normal flow filtration device is a simple and cost-effective single-use solution for the scales (3–200 L) required in regenerative medicine applications.