Renal stem cells: Fact or science fiction?

Department of Biological Sciences, University of Notre Dame, IN 46556, USA.
Biochemical Journal (Impact Factor: 4.4). 06/2012; 444(2):153-68. DOI: 10.1042/BJ20120176
Source: PubMed


The kidney is widely regarded as an organ without regenerative abilities. However, in recent years this dogma has been challenged on the basis of observations of kidney recovery following acute injury, and the identification of renal populations that demonstrate stem cell characteristics in various species. It is currently speculated that the human kidney can regenerate in some contexts, but the mechanisms of renal regeneration remain poorly understood. Numerous controversies surround the potency, behaviour and origins of the cell types that are proposed to perform kidney regeneration. The present review explores the current understanding of renal stem cells and kidney regeneration events, and examines the future challenges in using these insights to create new clinical treatments for kidney disease.

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Available from: Kristen K McCampbell
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    • "How the regenerated tubule epithelium is formed, including the establishment of tight junctions in these cells, will be important to understand, both to appreciate in vivo mechanisms and to elucidate new therapeutic applications such as the emerging science of in vitro renal cell reprogramming (Morales and Wingert, 2014). Both the zebrafish embryonic and adult kidney are useful models for research about renal injury and regeneration (Diep et al., 2011; Gerlach et al., 2011; Hellman et al., 2010; Hentschel et al., 2005; Huang et al., 2013; Johnson et al., 2011; McCampbell et al., 2014; Zhou and Hildebrandt, 2012; Zhou et al., 2010). In particular, adult zebrafish possess a high capacity for renal regeneration after AKI in the nephron tubule (Diep et al., 2011; McCampbell and Wingert, 2014; Zhou et al., 2010). "
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    ABSTRACT: The kidney is comprised of nephrons—epithelial tubes with specialized segments that reabsorb and secrete solutes, perform osmoregulation, and produce urine. Different nephron segments exhibit unique combinations of ion channels, transporter proteins, and cell junction proteins that govern permeability between neighboring cells. The zebrafish pronephros is a valuable model to study the mechanisms of vertebrate nephrogenesis, but many basic features of segment gene expression in renal progenitors and mature nephrons have not been characterized. Here, we analyzed the temporal and spatial expression pattern of tight junction components during zebrafish kidney ontogeny. During nephrogenesis, renal progenitors show discrete expression domains of claudin (cldn) 15a, cldn8, occludin (ocln) a, oclnb, tight junction protein (tjp) 2a, tjp2b, and tjp3. Interestingly, transcripts encoding these genes exhibit dynamic spatiotemporal domains during the time when pronephros segment domains are established. These data provide a useful gene expression map of cell junction components during zebrafish nephrogenesis. As such, this information complements the existing molecular map of nephron segment characteristics, and can be used to characterize kidney development mutants as well as various disease models, in addition to aiding in the elucidation of mechanisms governing epithelial regeneration after acute nephron injury.
    Full-text · Article · Nov 2014 · Gene Expression Patterns
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    • "In humans, for example, the kidney is comprised of more than 20 different epithelial and mesenchymal cell types (Reilly et al., 2007). During embryogenesis, the renal lineages derive from the intermediate mesoderm (IM) and can be divided broadly into parenchymal (functional ) and stromal (supporting) cells (McCampbell and Wingert, 2012). Cooperation between these cell types enables the kidney to perform sophisticated physiological functions that include blood filtration, nitrogenous waste excretion, reabsorption of metabolites, regulation of acid–base levels, maintenance of osmotic balance, and the secretion of hormones (Reilly et al., 2007). "
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    ABSTRACT: During development, vertebrates form a progression of up to three different kidneys that are comprised of functional units termed nephrons. Nephron composition is highly conserved across species, and an increasing appreciation of the similarities between zebrafish and mammalian nephron cell types has positioned the zebrafish as a relevant genetic system for nephrogenesis studies. A key component of the nephron blood filter is a specialized epithelial cell known as the podocyte. Podocyte research is of the utmost importance as a vast majority of renal diseases initiate with the dysfunction or loss of podocytes, resulting in a condition known as proteinuria that causes nephron degeneration and eventually leads to kidney failure. Understanding how podocytes develop during organogenesis may elucidate new ways to promote nephron health by stimulating podocyte replacement in kidney disease patients. In this review, we discuss how the zebrafish model can be used to study kidney development, and how zebrafish research has provided new insights into podocyte lineage specification and differentiation. Further, we discuss the recent discovery of podocyte regeneration in adult zebrafish, and explore how continued basic research using zebrafish can provide important knowledge about podocyte genesis in embryonic and adult environments. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Sep 2014 · genesis
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    • "Historically, research about nephron segmentation has been impeded by the architectural complexity of the metanephros in mammals since this kidney form is composed of thousands to millions of nephrons (McCampbell & Wingert, 2012; Hallgrimsson et al., 2003). A new opportunity to study nephrogenesis emerged when scientific evidence was found supporting the conclusion that the zebrafish nephron also consists of a similarly segmented tubule, contrary to past belief concerning its lack of specialization (Wingert et al., 2007; Wingert & Davidson, 2008). "
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    ABSTRACT: The zebrafish has proven to be an important model organism for investigating numerous developmental topics, especially organogenesis. To date, the zebrafish has played an expanding role in aiding our understanding of the genetic intricacies that underlie renal development, a process that has been poorly understood in the past. The kidney is a vital organ that is responsible for maintaining fluid homeostasis and removing waste metabolites from the body. Current research has established that the segmentation patterning of the nephrons, which are the basic functional units of the kidney, is conserved between this teleost species and higher vertebrates, including mammals. This concept of conservation within the kidney was further exemplified by the identification of orthologous genes that are expressed during the dynamic cellular and morphological processes that occur throughout nephrogenesis. Continuing advances in molecular techniques, from morpholinos to TALENs and now CRISPRs, have fueled the increasing appeal of employing zebrafish in research. The future application of these technologies offers a valuable venue to study kidney development and holds promise to elucidate clinical interventions for a variety of renal diseases.
    Full-text · Chapter · Jun 2014
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