Adult renal Sca-1+Lin- multipotent progenitor cells support tubular
regeneration
Benjamin Dekel,1 Lior Zangi, 1 Elias Shezen, 1 Shlomit Reich-Zeliger, 1 Smadar
Eventov-Friedman, 1 Helena Katchman, 1 Jasmine Jacob-Hirsch, 2 Ninette
Amariglio, 2 Gideon Rechavi, 2 Raanan Margalit1 and Yair Reisner1
1
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
2
Department of Pediatric Hemato-Oncology and functional genomics, Sheba
Medical Center, Tel-Hashomer, Israel
Running title: Adult renal Sca-1+Lin- progenitor cells
Word count: 6113
Corresponding Author:
Yair Reisner, Weizmann Institute of Science, Dept. of Immunology, Rehovot, Israel.
Prof. Yair Reisner holds the Henry H. Drake Professorial Chair in Immunology.
Phone: +972-8-9344023: Fax: +972-8-9344145
E-mail: yair.reisner@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, we used stage-specific embryonic kidney progenitor tissue
to regenerate nephrons. Through fluorescence-activated cell sorting, microarray
analysis, in vitro differentiation assays, mixed lymphocyte reaction and a model of
ischemic kidney injury, we sought to identify and characterize multipotent organ
stem/progenitor cells in the developing and adult kidney.
Here, we report the existence of adult kidney – derived renal progenitor cells
expressing stem cell antigen – 1 (Sca-1) but lacking hematopoietic stem cell and
lineage markers. These cells, which are typically negative for pan-cytokeratin,
predominantly localize to the interstitium of the renal papillae, a presumed adult
kidney stem cell niche. Global gene profiling reveals enrichment for many genes
down-stream to developmental signaling molecules and self-renewal pathways, such
as TGF/BMP, Wnt or FGF, as well as for those involved in specification of
mesodermal lineages (MEF2A, YAF2, filamin). In vitro, they are plastic adherent,
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 contribute to kidney repair.
Our 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.