Hematopoietic Stem Cells Engraft in Untreated Transplant Recipients

We investigated the engraftment of hematopoietic stem cells in completely untreated transplant recipients to further study hematopoietic cell regulation and for possible inclusion in gene therapy protocols. Untreated female Balb/c recipients received a single infusion of male Balb/c marrow cells. Donor origin of the hematopoietic cells was determined by polymerase chain reaction (PCR), Southern and in situ hybridization analyses with Y-chromosome-specific probes. We found that up to 47% day 12 CFU-S (26.2 +/- 12.6%, mean +/- SD, range 13.3 to 46.7%), 7.3 +/- 5.5% CFU-GM and from 2.5 to approximately 10% nucleated marrow cells were of donor-origin at 8 weeks after marrow infusion. Our results indicate that hematopoietic stem cells can stably engraft in completely unconditioned recipients but, during the interval analyzed, have a low tendency to differentiate. Moreover, the data suggest that under steady-state conditions, niches for primitive hematopoietic cells present in the marrow microenvironment are not saturated, and are readily available. We conclude that the untreated-recipient transplant model, in conjunction with sensitive techniques for the detection of donor cells, provides a valuable means for studying hematopoietic stem cell regulation and indicates a need to reassess our understanding of the interactions between stem cells and the hematopoietic microenvironment.