Ex vivo expansion of transplantable human hematopoietic stem cells: where do we stand in the year 2000?
Ex vivo expansion of hematopoietic precursors, progenitors and stem cells represents the modern era of cellular therapeutics in the 21st century. For the last 10 years, increasing means for identifying and purifying hematopoietic stem cells and cytokines have facilitated and improved the development of ex vivo stem cell expansion technology. However, technology has not yet reached a stage where ex vivo-expanded hematopoietic progenitors and stem cells can be used routinely for replacement therapy. Lessons learned over the past 10 years from investigations focused at developing optimal ex vivo stem cell expansion systems have continued to a much greater understanding of stem cell biology. This knowledge has led to novel attempts at ex vivo expansion of hematopoietic precursors, progenitors, and stem cells, and should facilitate development of a new generation of cellular therapeutics. This review addresses recent progress toward development of clinically useful protocols for stem cell expansion. In addition, we discuss the results of a limited number of clinical trials that address the efficacy of such procedures. Three major areas of ex vivo stem cell expansion that impact clinical feasibility are discussed, including: (1) selection of an optimal stem cell population for expansion, (2) definition of the desired characteristics of the expanded stem cell population to be used for engraftment, and (3) development of new reagents and procedures for expansion and infusion of hematopoietic progenitors and stem cells.
Shih
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CC
Division of Hematology/Bone Marrow Transplantation, City of Hope National Medical Center, Beckman Research Institute at City of Hope, Duarte, CA 91010-3000, USA. cshih@coh.org
DiGiusto
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D
Forman
S J
SJ
D018929:Cell Culture Techniques / Q000379:methods; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000302:isolation & purification / Q000502:physiology; D016298:Hematopoietic Cell Growth Factors / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D011994:Recombinant Proteins / Q000627:therapeutic use
D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D011994:Recombinant Proteins