title: Splenectomy influences homing of transplanted stem cells in bone marrow-ablated mice.
abstract: Cell mobilization, a process that influences circulation, margination, and finally, homing play key roles in the regeneration processes mediated by stem cells. Recent studies as well as prior studies from our group indicate an important role of the spleen in hematopoietic reconstitution, but to date the role of the spleen in hematopoietic reconstitution has been unclear and it has not been precisely documented in ablated animals. Therefore, we undertook the present study to define more closely the role of the spleen in hematopoietic reconstitution in lethally irradiated mice. After transplantation of irradiated mice with lacZ+ -marked lin- / CD117+ bone marrow cells, we compared splenectomized mice (T(S), splenectomy performed prior to irradiation) to nonsplenectomized, irradiated mice (T(N)) as well as to normal (unirradiated) mice. Impaired hematopoietic reconstitution was observed in T(S) mice. Splenectomy markedly altered the distribution of hematopoietic stem cells, as demonstrated by fluorescence-activated cell sorting analysis of endogenous CD117+ cells in the thymus and bone marrow of recipients. Cell engraftment was demonstrated by histochemical and polymerase chain reaction analyses of recipient tissues. These experiments demonstrated that in T(S) animals, transplanted hematopoietic stem cells mobilized to extravascular tissues, particularly the gastrointestinal tract. The number of donor cells in recipient tissues continued to increase for 30 days after transplantation with the highest numbers observed in the T(S) group. DNA marking analysis led to the conclusion that engrafted cells were not only integrated into recipient tissues but were also capable of performing complex cellular processes, including proliferation and repair. Our results are consistent with the novel possibility that cellular repair markedly affects stem cell regenerative functions and that repair is markedly influenced by the integrity and presence of organs not directly involved in specific tissue regeneration processes, particularly the spleen.
authors.affiliation: Department of Oncology and Radiotherapy, Faculty of Medicine and Teaching Hospital, Charles University in Prague, Hradec Králové, Czech Republic. filip@fnhk.cz
authors.forename: Stanislav
authors.initials: S
authors.lastname: Filip
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Mokrý
authors.forename: Jiřina
authors.initials: J
authors.lastname: Vávrová
authors.forename: Dana
authors.initials: D
authors.lastname: Cížková
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Sinkorová
authors.forename: Stanislav
authors.initials: S
authors.lastname: Mičuda
authors.forename: Milan
authors.initials: M
authors.lastname: Bláha
authors.forename: Denis
authors.initials: D
authors.lastname: English
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000528:radiation effects*; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D005434:Flow Cytometry; D015870:Gene Expression; D006410:Hematopoiesis / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D018655:Lymphocyte Count; D051379:Mice; D057507:Mice, 129 Strain; D008822:Mice, Transgenic; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013156:Splenectomy / Q000379:methods*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D019009:Proto-Oncogene Proteins c-kit; D001616:beta-Galactosidase