Journal
BLOOD
Volume 119, Issue 15, Pages 3431-3439Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-12-398024
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Funding
- Stem Cell Network (SCN) of Canada
- Terry Fox Foundation
- Terry Fox Research Institute
- Canadian Institutes of Health Research
- Croucher Foundation (Hong Kong)
- SCN of Canada
- Michael Smith Foundation for Health Research
- Fonds de Recherche du Quebec-Sante (FRQS)
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Delayed recovery of mature blood cells poses a serious, expensive, and often life-threatening problem for many stem cell transplantation recipients, particularly if heavily pretreated and serving as their own donor, or having a CB transplantation as the only therapeutic option. Importantly, the different cells required to ensure a rapid, as well as a permanent, hematopoietic recovery in these patients remain poorly defined. We now show that human CB and mobilized peripheral blood (mPB) collections contain cells that produce platelets and neutrophils within 3 weeks after being transplanted into sublethally irradiated NOD/scid-IL-2R gamma c-null mice. The cells responsible for these 2 outputs are similarly distributed between the aldehyde dehydrogenase-positive and -negative subsets of lineage marker-negative CB and mPB cells, but their overall frequencies vary independently in individual samples. In addition, their total numbers can be seen to be much (> 30-fold) lower in a single average CB transplantation compared with a single average mPB transplantation (normalized for a similar weight of the recipient), consistent with the published differential performance in adult patients of these 2 transplantation products. Experimental testing confirmed the clinical relevance of the surrogate xenotransplantation assay for quantifying cells with rapid platelet regenerative activity, underscoring its potential for future applications. (Blood. 2012;119(15):3431-3439)
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