Irrespective of scientific discipline, everyone is aware of the blood-brain barrier. Since its proposal in 1900 by Max Lewandowsky, and later confirmation of its discovery in the 1960s – facilitated by the advancement of the scanning electron microscope – it has gripped physiologists and contributed to significant advancements in our understanding of pharmacokinetics. However, as stressed by Harvard’s George Daley, developments in fundamental stem cell science now present another barrier to haematologists: the “blood-clinic barrier”.
The production of synthetic blood from human cells is slowly becoming a genuine prospect for the cell therapy community, with licenses to manufacture clinical grade synthetic human blood granted only days ago to Scottish company Roslin Cells. This complements on-going DARPA funding for U.S. based Arteriocyte to develop cell-based blood substitutes for servicemen. Nevertheless, there are a number of multi-stakeholder challenges separating this scientific promise from a widely accessible clinical practice – a number of which are scientific in nature.
- Development of Functional Blood Units: The derivation of HSCs from ESCs is well studied, promoting genes, including Cdx4 and HoxB4, into the vernacular. To date, however, HSCs generated in such a manner have not been representative of in vivo HSCs; in part, due to their tendency to exhibit a myeloid bias.
- Mechanism of Hematopoietic Ontogeny: Despite the familiar diagrams of the haematopoietic differentiation pathway, we are still unable to effectively and reproducibly control HSC proliferation and differentiation in vitro, in a manner that would yield sufficient cells to support a therapeutic and meet the expectations relating to critical quality attributes (CQAs) required by a regulator.
- Culture Systems: At an elementary level, blood is a fluid and as such is subject to three- dimensional hydro-dynamic forces. Conversely, the majority of laboratory scale efforts to produce cell-based blood products relies on two-dimensional static cultures. Subsequently, the bioprocess forces experienced by cells are poorly representative of in vivo conditions, contributing to differences in cellular polarity during formation and differences in subsequent cellular functionality.
- Our Choice of Cell: While we are aware of the characteristics of the cells we wish to reproduce in the haematopoietic lineage, we are less certain of the optimal characteristics of the optimal cell(s) to be used as the source material for such a process. For example, a major challenge to utilizing cells already committed someway down the haematopoietic lineage is limitations in their ability to self-renew.
Therefore, while stem cell sources offer great long-term promise as a route to scalable and effective synthetic blood products, and are currently experiencing a peak of interest, it is important to remember that a number of factors constituting the “blood-clinic barrier” remain. It is our shared responsibility as members of the cell therapy industry to work collaborative and efficiently to resolve these challenges.
Latest posts by David Brindley (see all)
- If cell therapy isn’t about the cells or the therapy, what is it about? - November 19, 2014
- Revolution and reimbursement in the cell therapy industry - November 13, 2014
- Of seismic waves and closing days: take home messages - October 1, 2014