chapter  7
36 Pages

Bioreactors for the Cultivation of Hematopoietic Stem and Progenitor Cells

WithMarta H.G. Costa, Frederico Castelo Ferreira, Joaquim M. S. Cabral, Cláudia Lobato da Silva

Transplantation of hematopoietic stem and progenitor cells (HSPC) has been used as a therapeutic option to treat several hemato-oncological diseases. To extend the number of patients that could benefit from HSPC-based therapies, robust bioprocesses need to be implemented for HSPC expansion and/or differentiation. In particular, the clinical use of umbilical cord blood (UCB) as a source of HSPC has been hindered by the low cell numbers available for transplantation. The implementation of HSPC-based therapies, namely using UCB cells, will require the development of scalable cultivation platforms. Herein, we review several culture parameters and tailored bioreactor configurations that would contribute towards the establishment of robust and scalable bioprocesses to expand HSPC. As microenvironment cues are critical to determine self-renewal versus differentiation decisions of primitive cells, different cytokine cocktails, oxygen tensions, pH, cell densities, and medium exchange schemes, either supported by stroma-based co-cultures or integrated in liquid suspension systems, could be explored to achieve clinically relevant cell numbers, particularly when aided by automated and closed-system bioreactors. The implementation of bioengineering strategies, combined with an increased knowledge of cellular biology principles, will enhance the quality and safety of HSPC-based products in a cost-effective manner, accelerating the clinical development of these cell-based therapies.