Engraftment of syngeneic bone marrow is not more efficient after intrafemoral transplantation than after traditional intravenous administration.
OBJECTIVE
Hematopoietic stem cells are key elements for life-long production of mature blood cells. The success of clinical stem cell transplantation may be improved when the number of stem cells that engraft after transplantation can be increased. Here, we investigated in a syngeneic mouse model whether engraftment and reconstitution can be improved by transplantation directly into the bone marrow.


METHODS
In this study, we directly compared syngeneic transplantation of hematopoietic stem cells into the bone marrow with intravenous administration and assessed reconstitution kinetics and engraftment by bioluminescent imaging and chimerism determination.


RESULTS
Surprisingly, only about 10% of cells injected directly into the femur (intrafemoral, IF) could be retrieved within 5 minutes after injection. Only in the first 48 hours after transplantation, engraftment in IF-transplanted animals was higher compared with intravenous injection. However, at all later time points no differences could be detected using whole body bioluminescence or measuring blood cell reconstitution. Most importantly, we found that IF-transplanted cells did not outcompete cells transplanted intravenously when cotransplanted in the same recipient.


CONCLUSIONS
In conclusion, IF transplantation in a murine syngeneic setting revealed no enhanced engraftment. Previous reports on IF transplantation may have relied on escape from immune rejection in xenogeneic or allogeneic models. Therefore, we conclude that stem cells can find the proper microenvironment irrespective of the route of administration.
van Os
Ronald
R
Department of Cell Biology, Section Stem Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands. r.p.van.os@med.umcg.nl
Ausema
Albertina
A
Dontje
Bert
B
van Riezen
Manon
M
van Dam
Gooitzen
G
de Haan
Gerald
G
D000818:Animals; D001853:Bone Marrow / Q000601:surgery*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005269:Femur / Q000601:surgery; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D007275:Injections, Intravenous; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D013997:Time Factors; D018183:Transplantation Chimera / Q000097:blood; D014185:Transplantation, Isogeneic; D014916:Whole-Body Irradiation
D008156:Luciferases