Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture.
Recent studies describe beneficial effects of bone marrow-derived mesenchymal stem cell infusion in animal models as well as in patients. However, data on the homing abilities of primary and culture-expanded MSC are lacking. In order to systematically investigate MSC homing we compared the fate of both primary and cultured MSC in a syngeneic mouse model. Twenty-four hours after transplantation of uncultured EGFP-transgenic MSC into sublethally irradiated mice, as many as 55-65% of injected CFU-F were recovered from the BM and 3.5-7% from the spleen. In the subsequent 4 weeks these donor CFU-F expanded 100-fold, which resulted in a normalization of femoral and splenic CFU-F numbers. This highly efficient homing of primary CFU-F contrasted with the defective homing of MSC following culture. Following their infusion immortalized multipotent syngeneic stromal cells were undetectable in BM, spleen, lymph nodes or thymus. Remarkably, following transplantation of primary MSC that had been cultured for only 24 h the seeding fraction in the BM was reduced to 10%, while after transplantation of 48 h cultured primary MSC no CFU-F were detected in the lymphohematopoietic organs. These data suggest that in vitro propagation of BM-derived MSC dramatically decreases their homing to BM and spleen.
Rombouts
W J C
WJ
Department of Haematology, Erasmus Medical Center, Rotterdam, The Netherlands.
Ploemacher
R E
RE
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005456:Fluorescent Dyes; D006085:Graft Survival; D049452:Green Fluorescent Proteins; D006801:Humans; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017978:Receptors, Growth Factor / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D015703:Antigens, CD; D005456:Fluorescent Dyes; D008164:Luminescent Proteins; D017978:Receptors, Growth Factor; D049452:Green Fluorescent Proteins