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  • Distinct but phenotypically heterogeneous human cell populations produce rapid recovery of platelets and neutrophils after transplantation.

    Blood. 119(15):3431-9. doi: 10.1182/blood-2011-12-398024. April 12, 2012. View on PubMed.
  • Authors

    Cheung AM, Leung D, Rostamirad S, Dhillon K, Miller PH, Droumeva R, Brinkman RR, Hogge D, Roy DC, and Eaves CJ
  • Abstract

    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-2Rγc-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.

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