Paul H Miller1, David J H F Knapp, Connie J Eaves. 1. Terry Fox Laboratory, British Columbia Cancer Agency and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Abstract
PURPOSE OF REVIEW: Transplantation of hematopoietic cells is now a well established clinical procedure, although optimal outcomes are not always obtained. This reflects insufficient knowledge of the different subsets of primitive cells required to achieve a rapid and permanent recovery of mature blood cell production. Here we review recent findings that extend our understanding of these cells and their regulation, and implications for the ex-vivo expansion of these cells. RECENT FINDINGS: Separate subsets of platelet and neutrophil lineage-restricted human hematopoietic cells with rapid but transient repopulating activities have been identified, thus adding to previous evidence of short-term repopulating cells that generate both of these lineages. New studies also suggest intrinsically determined heterogeneity in differentiation potentialities that are sustained at the stem cell level, and have revealed new ways their self-renewal can be influenced. SUMMARY: Hematopoietic repopulation posttransplant is highly complex both in terms of the differing numbers and types of cells required for optimal hematopoietic recoveries and the factors that will determine the composition and behavior of a given inoculum. Successful ex-vivo expansion protocols will, thus, need to incorporate conditions that will produce adequate numbers of all cell types required with retention of their full functionality.
PURPOSE OF REVIEW: Transplantation of hematopoietic cells is now a well established clinical procedure, although optimal outcomes are not always obtained. This reflects insufficient knowledge of the different subsets of primitive cells required to achieve a rapid and permanent recovery of mature blood cell production. Here we review recent findings that extend our understanding of these cells and their regulation, and implications for the ex-vivo expansion of these cells. RECENT FINDINGS: Separate subsets of platelet and neutrophil lineage-restricted human hematopoietic cells with rapid but transient repopulating activities have been identified, thus adding to previous evidence of short-term repopulating cells that generate both of these lineages. New studies also suggest intrinsically determined heterogeneity in differentiation potentialities that are sustained at the stem cell level, and have revealed new ways their self-renewal can be influenced. SUMMARY: Hematopoietic repopulation posttransplant is highly complex both in terms of the differing numbers and types of cells required for optimal hematopoietic recoveries and the factors that will determine the composition and behavior of a given inoculum. Successful ex-vivo expansion protocols will, thus, need to incorporate conditions that will produce adequate numbers of all cell types required with retention of their full functionality.
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