Stem Cell-Derived Blood Products for Transfusion Workshop Summary

The workshop was convened on September 27, 2013 chaired by Dr. George Daley and included expert presentations on stem cell biology and differentiation, cell processing, transfusion medicine, and the development of stem cell-derived red blood cell, platelet, and myeloid progenitor products. In addition, representatives from biotechnology firms, BARDA, FDA, the Army Blood Bank, the NIH Center for Regenerative Medicine, and the California Institute of Regenerative Medicine were present and made important contributions to the discussions. The workshop participants identified areas where NHLBI support is needed to address remaining research questions both in the basic arena and to enable translation through improved cell production and processing.

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

George Daley, MD, Chair…………………

Boston Children's Hospital

Stewart Abbot, PhD…………………………

Celgene

Linzhao Cheng, PhD…………………………

Johns Hopkins University

Koji Eto, MD, PhD……………………………

Kyoto University

Adrian Gee, MI Biol, PhD…………………

Baylor College of Medicine

COL Richard Gonzales………………………

Army Blood Bank

Alan D. Michelson, MD………………………

Boston Children's Hospital

W. Beau Mitchell, MD………………………

New York Blood Center

George Murphy, PhD…………………………

Boston University School of Medicine

Shibani Pati, MD, PhD………………………

Blood Systems Research Institute

Mahendra Rao, MD, PhD…………………

NIH Center for Regenerative Medicine

Thorsten M. Schlaeger, PhD……………

Boston Children's Hospital

Leslie Silberstein, MD………………………

Brigham and Women's Hospital

Sohel Talib, PhD………………………………

California Institute of Regenerative Medicine

William Reed, MD……………………………

Cellerant Therapeutics

 

Planning Committee

Other representatives

Project Officers

Mary Homer, BARDA

John Thomas, PhD

Deborah Hursh, FDA

Shimian Zou, PhD

Xiaobin (Victor) Lu, FDA

 

Committee Members

Meeting Planners

Simone Glynn, MD

Petronella Barrow

Nancy DiFronzo, PhD

Kathy Fain

Catherine Levy, RN

Carol Sadler

Traci Mondoro, PhD

 

Phyllis Mitchell, MPH

 

Liz Wagner, MS

 

Lis Welniak, PhD

 




Last Updated March 2014




Skip footer links and go to content
Twitter iconTwitterExternal link Disclaimer         Facebook iconFacebookimage of external link icon         YouTube iconYouTubeimage of external link icon         Google+ iconGoogle+image of external link icon