Haematopoietic culture systems

Abstract

Haematopoietic stem cells have been applied successfully in the clinic for over 30 years. This experience, the relative ease with which HSCs can be identified and obtained from a variety of sources and the potential plasticity of these cells makes them ideal for use in haematologic and non-haematologic conditions. Despite these advantages and the significant progress that has been made in the characterisation of factors that govern haematopoiesis, enrichment and ex vivo expansion of repopulating (and possibly plastic) HSCs remains elusive. Conventional 2-D cultures are insufficient to meet the complex demands required and small deviations in the culture parameters can profoundly affect the final cell output. The application of factorial and composite designs to HSC cultures is required in order to fully appreciate the effects and interdependence of stimulatory and inhibitory factors as well as the culture parameters on haematopoietic culture systems. Furthermore, ex vivo expanded HSCs must be safe to use in humans and meet regulations guided by good manufacturing practice (GMP) requirements for clinical therapeutics which includes the development of suitable, closed culture systems that can be easily controlled and monitored. The engineering of optimal haematopoietic cell culture systems requires the design of new expansion systems that mimic the in vivo bone marrow environment that is able to self-regulate and operate under reliable and reproducible conditions. Such a system would offer a broad spectrum of possibilities for different culture strategies in the cultivation of various cell types - from stem cells to differentiated cells for gene, cellular, and tissue therapies. © 2005 Springer.