Stem Cell-Derived Blood Products for Transfusion

Challenges before us

The goal is to use stem cell technology to produce blood cells in vitro, such as hematopoietic stem cells, red blood cells, platelets, or granulocytes. This approach holds the promise of an abundant number of uniform cells with defined biological properties free of reactive antigens and infectious agents. With the current state of the science it is already possible to derive blood cells in the laboratory and stem cell-derived red blood cells have been safety tested in humans. What is required is to advance the remaining aspects of basic research and cell processing to enable clinical-grade manufacture in a feasible, cost-effective manner. Prior to use, a strategy for clinical assessment is required that includes both functional and safety measures. In the end, the true determinant of this new approach will be medical needs met and the range of uses it can fulfill.

Research needs

• Molecular mechanisms of cellular heterogeneity; this can be addressed by single cell analysis
• Molecular mechanisms of red cell and platelet maturation
  • Globin gene switching, enucleation
  • Bioreactor, shear and flow mediated platelet maturation
• Animal models to validate clinical efficacy of stem cell-based products
  • To qualify in vitro-generated product
  • For example, for platelets, demonstrate clinical hemostatic efficacy
• Assessment of malignancy, toxicity, and efficacy; definition of the right first human indications
• Costs
  • Near-term: justified for unique high- value clinical indications within academic medical centers
  • Long-term: need transformative advances

Future opportunities

• Driving costs down may enable commercial viability
  • New methods may bypass the need for expensive cytokines
  • Delivery of progenitors may mean that terminally differentiated cells are not required
  • Critical indications can justify higher production costs
• NK cells, Tregs, chimeric antigen receptor-modified T cells may be high-value cell products
• Improved reporters and improved methods for differentiation and purification may lower costs
• Opportunities driving increased value
  • Overcoming HLA antibody sensitization in multiply transfused patients
  • Avoiding anti-HLA antibodies that can mediate often fatal transfusion-related acute lung injury (TRALI)
  • Identifying disease specific applications
• Hematopoietic stem cells or red blood cells might be matured in animals to lower costs
• The shelf-life and viability of stem cell-derived cell products might be longer. For example, the five-day shelf-life of current platelet products is a major issue.
• Potential collaborative partners in Federal and State government: DOD, DARPA, BARDA, CIRM

Working Group Members

Last Updated March 2014