Isolation and characterization of nontubular Sca-1+Lin - multipotent stem/progenitor cells from adult mouse kidney

Benjamin Dekel, Lior Zangi, Elias Shezen, Shlomit Reich-Zeliger, Smadar Eventov-Friedman, Helena Katchman, Jasmin Jacob-Hirsch, Ninette Amariglio, Gideon Rechavi, Raanan Margalit, Yair Reisner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 β1-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-β/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-β). In vitro, they are plastic adherent and slowly proliferating and result in inhibition of alloreactive CD8+ T cells, indicative of an immuneprivileged 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.

Original languageEnglish
Pages (from-to)3300-3314
Number of pages15
JournalJournal of the American Society of Nephrology : JASN
Issue number12
StatePublished - Dec 2006
Externally publishedYes


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