A mouse model to study organ homing behaviour of haemopoietic progenitor cells reveals high selectivity but low efficiency of multipotent progenitors to home into haemopoietic organs.
To study the homing behaviour of an enriched multipotent primitive haemopoietic progenitor cell (HPC) population in mice, undifferentiated murine factor-dependent multipotent HPCs (FDCP-mix), stably transfected with the green fluorescence protein gene, were intravenously injected into congenic mice. After 2 or 24 h, cell suspensions were prepared from bone marrow, spleen, lung, liver, muscle, colon, kidney, brain or blood of the mice and analysed by flow cytometry. Using direct quantifiable determination of total HPC numbers homed per organ and a method to estimate the degree of organ contamination by HPC that were present in blood vessels within the organs before preparation, the highest absolute numbers of HPC were detected in the liver and lungs at 2 h but this was sharply decreased at 24 h, whereas HPC selectively accumulated in the bone marrow and spleen at 24 h after transplantation. Only a few HPC were detected in other organs. The seeding efficiency of homed FDCP-mix HPC to the bone marrow and spleen was approximately 1.5% and ranged between that of primary whole bone marrow cells and lineage-depleted freshly isolated bone marrow cells. Pretreatment of HPC with inhibitors of signal transduction indicated that short-term homing of multipotent HPC into haemopoietic organs is an active process requiring co-ordinated intracellular signalling through Rho family small GTPases and protein kinases. Thus, short-term homing of FDCP-mix HPC into haemopoietic organs is of low efficiency but high selectivity, and provides a system to analyse the mechanisms and manipulation of primitive HPC which saves large numbers of donor animals.
Henschler
R
R
Institute of Transfusion Medicine and Immune Haematology, German Red Cross Blood Centre, Frankfurt, Germany. rhenschler@bsdhessen.de
Fehervizyova
Z
Z
Bistrian
R
R
Seifried
E
E
D000818:Animals; D001854:Bone Marrow Cells; D002452:Cell Count; D002465:Cell Movement; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008099:Liver / Q000166:cytology*; D008164:Luminescent Proteins / Q000235:genetics; D008168:Lung / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D023421:Models, Animal; D039902:Multipotent Stem Cells / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D014162:Transfection
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins