title: Evidence that the population of quiescent bone marrow-residing very small embryonic/epiblast-like stem cells (VSELs) expands in response to neurotoxic treatment.
abstract: The concept that bone marrow (BM)-derived cells may participate in neural regeneration remains controversial, and the identity of the specific cell type(s) involved remains unknown. We recently reported that the adult murine BM contains a highly mobile population of Sca-1(+) Lin(-) CD45(-) cells known as very small embryonic/epiblast-like stem cells (VSELs) that express several markers of pluripotency such as Oct-4. In the BM microenvironment, these cells are kept quiescent because of epigenetic modification of certain paternally imprinted genes. However, as reported, these cells can be mobilized in mice in an experimental model of stroke and express several genes involved in neurogenesis while circulating in peripheral blood (PB). In the current work, we employed a model of toxic brain damage, which is induced by administration of kainic acid, to see not only whether VSELs can be mobilized into PB in response to this neurotoxin, but, more importantly, whether they proliferate and expand in BM tissue. We report here for the first time that brain damage leads to activation and expansion of the BM pool of quiescent VSELs, which precedes their subsequent egress into PB. Harnessing these cells in neural tissue regeneration is currently one of the challenges in regenerative medicine.
authors.affiliation: Department of Physiology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Grymula
authors.forename: Maciej
authors.initials: M
authors.lastname: Tarnowski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Piotrowska
authors.forename: Malwina
authors.initials: M
authors.lastname: Suszynska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Mierzejewska
authors.forename: Sylwia
authors.initials: S
authors.lastname: Borkowska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Fiedorowicz
authors.forename: Magda
authors.initials: M
authors.lastname: Kucia
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology*; D001927:Brain Diseases / Q000139:chemically induced / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D053595:Embryonic Stem Cells / Q000502:physiology*; D005434:Flow Cytometry; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008810:Mice, Inbred C57BL
chemical_list: D007608:Kainic Acid
keywords: VSELs; kainic acid; neurotoxicity; stem cell mobilization