Ex vivo expansion of primitive hematopoietic cells for cellular therapies: An overview

Todd A. McAdams, Craig E. Sandstrom, William M Miller, James G. Bender, E. Terry Papoutsakis*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Sources of hematopoietic cells for bone marrow transplantation are limited by the supply of compatible donors, the possibility of viral infection, and autologous (patient) marrow that is depleted from prior chemo- or radiotherapy or has cancerous involvement. An ex vivo system to amplify hematopoietic progenitor cells could increase the number of patients eligible for autologous transplant, allow use of cord blood hematopoietic cells to repopulate an adult, reduce the amount of bone marrow and/or mobilized peripheral blood stem and progenitor cells required for transplantation, and reduce the time to white cell and platelet engraftment. The cloning of hematopoietic growth factors and the identification of appropriate conditions has enabled the development of successful ex vivo hematopoietic cell cultures. Purification systems based on the CD34 marker (which is expressed by the most primitive hematopoietic cells) have proven an essential tool for research and clinical applications. Present methods for hematopoietic cultures (HC) on stromal (i.e. accessory cells that support hematopoiesis) layers in flasks lack a well-controlled growth environment. Several bioreactor configurations have been investigated, and a first generation of reactors and cultures has reached the clinical trial stage. Our research suggests that perfusion conditions improve substantially the performance of hematopoietic reactors. We have designed and tested a perfusion bioreactor system which is suitable for the culture of non-adherent cells (without stromal cells) and readily scaleable for clinical therapies. Eliminating the stromal layer eliminates the need for a stromal cell donor, reduces culture time, and simplifies the culture system. In addition, we have compared the expansion characteristics of both mononuclear and CD34+ cells, since the latter are frequently assumed to give a superior performance for likely transplantation therapies.

Original languageEnglish (US)
Pages (from-to)133-146
Number of pages14
JournalCytotechnology
Volume18
Issue number1-2
DOIs
StatePublished - Jan 1 1995

Keywords

  • bioreactor
  • clinical therapies
  • cytokines
  • ex vivo expansion
  • hematopoietic culture
  • stroma

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    McAdams, T. A., Sandstrom, C. E., Miller, W. M., Bender, J. G., & Papoutsakis, E. T. (1995). Ex vivo expansion of primitive hematopoietic cells for cellular therapies: An overview. Cytotechnology, 18(1-2), 133-146. https://doi.org/10.1007/BF00744329