Accelerated and long-term hematopoietic engraftment in mice transplanted with ex vivo expanded bone marrow.
Using a murine experimental model, we investigated whether ex vivo expansion of BM grafts under IL-3/IL-6 stimulation accelerates the early hematopoietic recovery of recipients of BM transplants. To facilitate the ex vivo expansion of hematopoietic progenitors, BM was first enriched in proliferatively active hematopoietic stem cells by a single treatment with 5-fluorouracil (5FU) 4 days prior to the BM harvest. The results showed that the number of CFU-GM and CFU-S12 progenitors in the graft was significantly increased (56-fold and 14-fold, respectively), as a result of a 3 day incubation in the presence of IL-3 and IL-6. Daily analysis of animals transplanted with 5 x 10(4) BM cells, either freshly harvested or expanded for 3 days, showed that the expanded grafts consistently allowed a faster hematopoietic recovery of recipients. Differences between both groups of transplanted animals were most evident when the number of either femoral or splenic CFU-GMs were compared, with increases close to 70-fold at the fifth day of engraftment being observed. Similarly, mice transplanted with expanded grafts showed a hastened recovery in the cellularity of both organs that was most significant during the second week following transplantation, with maximal increases of 15 and 40-fold in the BM and spleen, respectively. Differences in peripheral leukocyte numbers between both groups of recipients were much less remarkable than those observed in the hematopoietic organs, although from the nadir period to the 11th day post-transplantation differences ranging from twofold to sixfold were apparent, consistent with a higher rate of mouse survival.(ABSTRACT TRUNCATED AT 250 WORDS)
Serrano
F
F
Unidad de Biologiá Molecular y Celular, CIEMAT, Madrid, Spain.
Varas
F
F
Bernad
A
A
Bueren
J A
JA
D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000379:methods*; D002478:Cells, Cultured; D005472:Fluorouracil / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016019:Survival Analysis
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D015850:Interleukin-6; D005472:Fluorouracil