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Received February 21, 2005
Accepted on August 30, 2006

BASIC SCIENCE: Cell Biology

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 ^*, and Yair Reisner ^*1

*Department of Immunology, Weizmann Institute of Science, Rehovot, and Department of Pediatric Hemato-Oncology and Functional Genomics, Sheba Medical Center, Tel-Hashomer, Israel

¹ To whom correspondence should be addressed. E-mail: yair.reisner{at}weizmann.ac.il.

	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 1-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-/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-). 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.

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