Accurate hematopoietic stem cell frequency estimates by fitting multicell Poisson models substituting to the single-hit Poisson model in limiting dilution transplantation assays

Abstract

Limiting dilution transplantation assay (LDTA) is considered as the gold standard method to assess hematopoietic stem cell (HSC) content. Traditionally, HSC frequency estimates are based on the single-hit Poisson model (SHPM), which posits that one donor HSC is sufficient to generate a progeny of detectable differentiated cells above a threshold value in hosts. However, there is no clear support for this statement, and it is receivable that more than one donor HSC may be necessary to provide detectable reconstitution in hosts above the threshold level for detection, usually 0.5% to 1% of donor-derived cells. To address this hypothesis, we evaluated the ability of a class of multiCell Poisson models (C≥1PMs) to fit to LDTAs. In 7 of the 8 reanalyzed LDTAs, C≥1PMs plausibly compete with the traditional SHPM. Model averaging across the set of plausible models gives 1.32- to 5.88-fold increases in HSC frequencies compared with the SHPM. © 2010 by The American Society of Hematology.