title: The adult human brain harbors multipotent perivascular mesenchymal stem cells.
abstract: Blood vessels and adjacent cells form perivascular stem cell niches in adult tissues. In this perivascular niche, a stem cell with mesenchymal characteristics was recently identified in some adult somatic tissues. These cells are pericytes that line the microvasculature, express mesenchymal markers and differentiate into mesodermal lineages but might even have the capacity to generate tissue-specific cell types. Here, we isolated, purified and characterized a previously unrecognized progenitor population from two different regions in the adult human brain, the ventricular wall and the neocortex. We show that these cells co-express markers for mesenchymal stem cells and pericytes in vivo and in vitro, but do not express glial, neuronal progenitor, hematopoietic, endothelial or microglial markers in their native state. Furthermore, we demonstrate at a clonal level that these progenitors have true multilineage potential towards both, the mesodermal and neuroectodermal phenotype. They can be epigenetically induced in vitro into adipocytes, chondroblasts and osteoblasts but also into glial cells and immature neurons. This progenitor population exhibits long-term proliferation, karyotype stability and retention of phenotype and multipotency following extensive propagation. Thus, we provide evidence that the vascular niche in the adult human brain harbors a novel progenitor with multilineage capacity that appears to represent mesenchymal stem cells and is different from any previously described human neural stem cell. Future studies will elucidate whether these cells may play a role for disease or may represent a reservoir that can be exploited in efforts to repair the diseased human brain.
authors.affiliation: Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden. gesine.paul@med.lu.se
authors.forename: Gesine
authors.initials: G
authors.lastname: Paul
authors.forename: Ilknur
authors.initials: I
authors.lastname: Özen
authors.forename: Nicolaj S
authors.initials: NS
authors.lastname: Christophersen
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinbothe
authors.forename: Johan
authors.initials: J
authors.lastname: Bengzon
authors.forename: Edward
authors.initials: E
authors.lastname: Visse
authors.forename: Katarina
authors.initials: K
authors.lastname: Jansson
authors.forename: Karin
authors.initials: K
authors.lastname: Dannaeus
authors.forename: Catarina
authors.initials: C
authors.lastname: Henriques-Oliveira
authors.forename: Laurent
authors.initials: L
authors.lastname: Roybon
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Anisimov
authors.forename: Erik
authors.initials: E
authors.lastname: Renström
authors.forename: Mikael
authors.initials: M
authors.lastname: Svensson
authors.forename: Anders
authors.initials: A
authors.lastname: Haegerstrand
authors.forename: Patrik
authors.initials: P
authors.lastname: Brundin
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002552:Cerebral Ventricles / Q000166:cytology; D002999:Clone Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D039902:Multipotent Stem Cells / Q000166:cytology*; D019579:Neocortex / Q000166:cytology; D020286:Pericytes / Q000166:cytology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D020797:Receptor, Platelet-Derived Growth Factor beta