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Spontaneous circulation of myeloid-lymphoid–initiating cells and SCID-repopulating cells in sickle cell crisis
Christopher E.D. Lamming, … , Robert P. Hebbel, Catherine M. Verfaillie
Christopher E.D. Lamming, … , Robert P. Hebbel, Catherine M. Verfaillie
Published March 15, 2003
Citation Information: J Clin Invest. 2003;111(6):811-819. https://doi.org/10.1172/JCI15956.
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Article

Spontaneous circulation of myeloid-lymphoid–initiating cells and SCID-repopulating cells in sickle cell crisis

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Abstract

The only curative therapy for sickle cell disease (SCD) is allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy approaches for autologous HSC transplantation are being developed. Although earlier engraftment is seen when cells from GCSF-mobilized blood are transplanted than when bone marrow is transplanted, administration of GCSF to patients with SCD can cause significant morbidity. We tested whether primitive hematopoietic progenitors are spontaneously mobilized in the blood of patients with SCD during acute crisis (AC-SCD patients). The frequency of myeloid-lymphoid–initiating cells (ML-ICs) and SCID-repopulating cells (SRCs) was significantly higher in blood from AC-SCD patients than in blood from patients with steady-state SCD or from normal donors. The presence of SRCs in peripheral blood was not associated with detection of long-term culture–initiating cells, consistent with the notion that SRCs are more primitive than long-term culture–initiating cells. As ML-ICs and SRCs were both detected in blood of AC-SCD patients only, these assays may both measure primitive progenitors. The frequency of ML-ICs also correlated with increases in stem cell factor, GCSF, and IL-8 levels in AC-SCD compared with steady-state SCD and normal-donor sera. Because significant numbers of ML-ICs and SRCs are mobilized in the blood without exogenous cytokine treatment during acute crisis of SCD, collection of peripheral blood progenitors during crisis may yield a source of autologous HSCs suitable for ex-vivo correction by gene therapy approaches and subsequent transplantation.

Authors

Christopher E.D. Lamming, Lance Augustin, Mark Blackstad, Troy C. Lund, Robert P. Hebbel, Catherine M. Verfaillie

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Figure 7

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More LTC-ICs, NK-ICs, and ML-ICs are mobilized in PB following GCSF+SCF ...
More LTC-ICs, NK-ICs, and ML-ICs are mobilized in PB following GCSF+SCF than following GCSF-only mobilization. Single CD34+CD38–Lin– cells, selected by FACS from lymphoma patients who received GCSF+SCF mobilization (66–132 wells plated) and lymphoma patients who received GSCF-only mobilization (66–132 wells plated), were plated in the ML-IC assay as previously described (24). The frequency of LTC-ICs was enumerated by overlaying of cultures with clonogenic medium after 5 weeks. Cells were maintained for 2 weeks in expansion medium, and progeny were replated in two LTC-IC and two NK-IC cultures. The frequency of NK-ICs was enumerated by harvesting of plates after 5 weeks and evaluation of the cells for presence of CD56+ NK cells or CD19+ B cells by FACS as previously described (24). An ML-IC was identified when progeny of the initial CD34+CD38–Lin– cell gave rise to at least one LTC-IC and at least one NK-IC. Significantly more NK-ICs and ML-ICs were present in CD34+CD38–Lin– cells from blood mobilized with GCSF+SCF than in those from blood mobilized with GCSF only. Differences in LTC-IC frequency between the two groups were not significant. Differences between the groups were evaluated by t test.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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