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

2012; Elsevier BV; Volume: 119; Issue: 15 Linguagem: Inglês

10.1182/blood-2011-12-398024

1528-0020

Alice M.S. Cheung, Donna Leung, Shabnam Rostamirad, Kiran Dhillon, Paul H. Miller, Radina Droumeva, Ryan R. Brinkman, Donna E. Hogge, Denis‐Claude Roy, Connie J. Eaves,

Platelet Disorders and Treatments

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.