Hematopoietic stem cell engraftment: a direct comparison between intramarrow and intravenous injection in nonhuman primates.
OBJECTIVE
Recent studies in the mouse model have shown improved engraftment of repopulating cells when cells were administered by intramarrow (IM) vs intravenous (IV) injection. Here we wished to determine if IM injection was feasible and would result in improved engraftment in a clinically relevant large animal model.


METHODS
We used a competitive repopulation assay to directly compare IM vs IV injection in four baboons. CD34+ autologous bone marrow cells were split into two equal fractions and transduced with either green fluorescent protein (GFP) or yellow fluorescent protein (YFP). Gene-marked cells were infused by IM or IV administration after myeloablative irradiation.


RESULTS
Peripheral blood granulocyte marking peaked at 2 to 3 weeks after transplantation and decreased thereafter before stabilizing. In all animals, marking levels of IM-injected cells (GFP) were lower than those of IV-injected cells (YFP) early after transplantation. However, in two of the four monkeys, GFP marking steadily increased after 2 months resulting in higher marking levels from IM-injected cells. In one animal, this trend sustained up to the last follow-up at 1 year after transplantation, with marking levels of 63.4% and 9.7% from IM- and IV-injected cells, respectively. Transplantation of both IM- and IV-injected CD34+ cells resulted in polyclonal multilineage engraftment.


CONCLUSIONS
Our data show efficient gene marking after IM injection and suggest a different engraftment profile for IM- vs IV-injected repopulating cells.
Jung
Chul Won
CW
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Beard
Brian C
BC
Morris
Julia C
JC
Neff
Tobias
T
Beebe
Katherine
K
Storer
Barry E
BE
Kiem
Hans-Peter
HP
D000818:Animals; D005819:Genetic Markers; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D007275:Injections, Intravenous; D051379:Mice; D016513:Mice, SCID; D010215:Papio; D012190:Retroviridae / Q000235:genetics; D016662:Virus Integration
D005819:Genetic Markers