Membrane-bound stem cell factor is a key regulator in the initial lodgment of stem cells within the endosteal marrow region.
OBJECTIVE
The transmembrane isoform of stem cell factor (tm-SCF) has been implicated in the adhesion of hemopoietic stem cells to the extracellular matrix within the bone marrow microenvironment in vitro. In addition, in vivo SCF has been shown to play a role in cell mobilization and migration. The aim of this study was to determine if SCF is an integral component of the hemopoietic "niche" of the bone marrow in situ.


METHODS
To analyze the role of tm-SCF in cell lodgment, purified populations of primitive progenitors and hemopoietic stem cells (HSC) were transplanted into a hemopoietic microenvironment devoid of tm-SCF, and the spatial distribution of engrafted cells was analyzed. In addition, populations of HSC were isolated using non-neutralizing and neutralizing antibodies to the SCF receptor c-kit, and their spatial distribution was analyzed post-transplant.


RESULTS
The data demonstrated a significant impairment in the lodgment of transplanted cells within the endosteal marrow region in mice lacking tm-SCF, with a reduction of almost 30% by 15 hours post-transplant. The role of tm-SCF was confirmed by analyzing the spatial distribution of HSC isolated using a neutralizing antibody to c-kit.


CONCLUSIONS
The data demonstrate that although tm-SCF does not appear to play a role in the homing of transplanted cells to the bone marrow, it is critical in the lodgment and detainment of HSC within their hemopoietic "niche."
Driessen
Rebecca L
RL
Stem Cell Laboratories, Peter MacCallum Cancer Centre, A'Beckett Street, Melbourne, Victoria 3000, Australia.
Johnston
Hayley M
HM
Nilsson
Susan K
SK
D000818:Animals; D001854:Bone Marrow Cells; D001856:Bone Marrow Examination; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion; D002633:Chemotaxis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D020033:Protein Isoforms / Q000502:physiology; D019009:Proto-Oncogene Proteins c-kit / Q000502:physiology; D019089:Stem Cell Factor / Q000235:genetics / Q000502:physiology*
D008565:Membrane Proteins; D020033:Protein Isoforms; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit