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

Blood. 2012 Apr 12;119(15):3431-9. doi: 10.1182/blood-2011-12-398024. Epub 2012 Feb 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Blood Cells / classification
  • Blood Cells / cytology*
  • Blood Cells / physiology*
  • Blood Platelets / physiology*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Infant, Newborn
  • Leukocyte Count
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Neutrophils / physiology*
  • Phenotype
  • Platelet Count
  • Transplantation, Heterologous