title: Isolation and characterization of nontubular sca-1+lin- multipotent stem/progenitor cells from adult mouse kidney.
abstract: Tissue engineering and cell therapy approaches aim to take advantage of the repopulating ability and plasticity of multipotent stem cells to regenerate lost or diseased tissue. Recently, stage-specific embryonic kidney progenitor tissue was used to regenerate nephrons. Through fluorescence-activated cell sorting, microarray analysis, in vitro differentiation assays, mixed lymphocyte reaction, and a model of ischemic kidney injury, this study sought to identify and characterize multipotent organ stem/progenitor cells in the adult kidney. Herein is reported the existence of nontubular cells that express stem cell antigen-1 (Sca-1). This population of small cells includes a CD45-negative fraction that lacks hematopoietic stem cell and lineage markers and resides in the renal interstitial space. In addition, these cells are enriched for beta1-integrin, are cytokeratin negative, and show minimal expression of surface markers that typically are found on bone marrow-derived mesenchymal stem cells. Global gene profiling reveals enrichment for many genes downstream of developmental signaling molecules and self-renewal pathways, such as TGF-beta/bone morphogenic protein, Wnt, or fibroblast growth factor, as well as for those that are involved in specification of mesodermal lineages (myocyte enhancer factor 2A, YY1-associated factor 2, and filamin-beta). In vitro, they are plastic adherent and slowly proliferating and result in inhibition of alloreactive CD8(+) T cells, indicative of an immune-privileged behavior. Furthermore, clonal-derived lines can be differentiated into myogenic, osteogenic, adipogenic, and neural lineages. Finally, when injected directly into the renal parenchyma, shortly after ischemic/reperfusion injury, renal Sca-1(+)Lin(-) cells, derived from ROSA26 reporter mice, adopt a tubular phenotype and potentially could contribute to kidney repair. These data define a unique phenotype for adult kidney-derived cells, which have potential as stem cells and may contribute to the regeneration of injured kidneys.
authors.affiliation: Weizmann Institute of Science, Department of Immunology, Rehovot, Israel.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dekel
authors.forename: Lior
authors.initials: L
authors.lastname: Zangi
authors.forename: Elias
authors.initials: E
authors.lastname: Shezen
authors.forename: Shlomit
authors.initials: S
authors.lastname: Reich-Zeliger
authors.forename: Smadar
authors.initials: S
authors.lastname: Eventov-Friedman
authors.forename: Helena
authors.initials: H
authors.lastname: Katchman
authors.forename: Jasmin
authors.initials: J
authors.lastname: Jacob-Hirsch
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Raanan
authors.initials: R
authors.lastname: Margalit
authors.forename: Yair
authors.initials: Y
authors.lastname: Reisner
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000302:isolation & purification*; D002454:Cell Differentiation; D005260:Female; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology*; D017493:Leukocyte Common Antigens / Q000302:isolation & purification*; D008297:Male; D008565:Membrane Proteins / Q000302:isolation & purification*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D046228:Microarray Analysis; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000276:immunology; D010641:Phenotype
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D017493:Leukocyte Common Antigens