W/Wv marrow stromal cells engraft and enhance early erythropoietic progenitors in unconditioned Sl/Sld murine recipients.
Transplantation of marrow stromal cells may provide a means of modulating hematopoiesis and serve as a form of cell therapy. We employed a murine transplant model using Sl/Sl(d) mice, which have macrocytic anemia due to defective expression of stem cell factor (SCF) on bone marrow stromal cells. Donor cells were derived from the complementary mutant strain W/W(v), which also exhibit anemia, due to mutations in c-kit, the SCF receptor expressed on hematopoietic stem cells. The strength of this model is that any correction of the Sl/Sl(d) anemia from the infusion of W/W(v) stromal cells can be attributed to the effect of the stromal cells and not to contaminating W/W(v) hematopoietic stem cells, a major concern in experiments involving wild-type animals. Cultured stromal cells were infused into unconditioned non-splenectomized Sl/Sl(d) mice. Engraftment of donor stromal cells reached levels of up to 1.0% of total marrow cells 4 months post transplant. However, stromal engraftment was not detectable in the spleen. Recipients of W/W(v) stroma showed a significant increase in the committed erythroid progenitors compared with those receiving Sl/Sl(d) stromal cells: 109 +/- 26 vs 68 +/- 5 CFU-E per 10(5) BMC, P = 0.002; 25 +/- 10 vs 15 +/- 5 BFU-E per 10(5) BMC, P = 0.037, for W/W(v) and Sl/Sl(d) stroma recipients, respectively. Despite this increase in erythroid progenitors, the anemia was not corrected. Our data suggest that in this murine model, splenic erythropoiesis may influence stromal cell therapy, and that higher levels of marrow engraftment may be necessary to obtain a clinically significant effect.
Bubnic
S J
SJ
Toronto General Research Institute, Toronto, ON, Canada.
Wang
X-H
XH
Clark
B R
BR
Keating
A
A
D000748:Anemia, Macrocytic / Q000235:genetics / Q000628:therapy; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002478:Cells, Cultured / Q000637:transplantation; D004909:Erythrocyte Indices; D015672:Erythroid Precursor Cells / Q000166:cytology*; D004920:Erythropoiesis; D005260:Female; D006085:Graft Survival; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D023421:Models, Animal; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000502:physiology*; D019089:Stem Cell Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology / Q000637:transplantation*; D019172:Transplantation Conditioning
D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit