A Side Order of Stem Cells: The SP Phenotype

Challen, Grant A.; Little, Melissa H.

doi:10.1634/stemcells.2005-0116

Cited by 437 publications

(354 citation statements)

References 72 publications

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“…Indeed, that report noted the presence of macrophages within the SP fraction (see Figure 4). All groups agree that, as for MSCs, SP cells shown multipotentiality and elicit an improvement in renal function via a humoral role, rather than by directly contributing to the replacement of renal tissue [73,74,76]. How this occurs is not clear, but the expression of renoprotective factors such as BMP7 has been reported to be higher in the SP than the non-SP fraction of the kidney [77].…”

Section: Progenitors Isolated Based Upon Cellular Behaviourmentioning

confidence: 81%

“…Dye efflux, being a dynamic procedure, will vary considerably according to isolation conditions, making the purity of the fraction variable. Hence, although the SP is enriched for multipotent progenitor cells, the heterogeneity of this population is acknowledged by most in the field [76]. Hishikawa et al [73] identified musculin/MyoR as a marker of SP, potentially allowing for improvements in isolation homogeneity.…”

Section: Progenitors Isolated Based Upon Cellular Behaviourmentioning

confidence: 99%

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Stem cell options for kidney disease

Hopkins

Rae

et al. 2008

The Journal of Pathology

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Chronic kidney disease (CKD) is increasing at the rate of 6-8% per annum in the US alone. At present, dialysis and transplantation remain the only treatment options. However, there is hope that stem cells and regenerative medicine may provide additional regenerative options for kidney disease. Such new treatments might involve induction of repair using endogenous or exogenous stem cells or the reprogramming of the organ to reinitiate development. This review addresses the current state of understanding with respect to the ability of non-renal stem cell sources to influence renal repair, the existence of endogenous renal stem cells and the biology of normal renal repair in response to damage. Understanding repair options via an understanding of renal developmentThe prevalence and incidence of chronic kidney disease (CKD) is increasing at 6-8% per annum in the USA alone, largely as a result of increased prevalence of diabetes and obesity [1]. To understand what might be possible with respect to cellular therapies or regenerative medicine for the kidney, one first needs to consider what is understood about normal renal development and response to injury. The kidney has been classically regarded as an organ with minimal cellular turnover and no capacity for regeneration. The subsequent identification of stem cells in a number of such organs, including the brain, has challenged this view. However, the dogma remains that the kidney reaches a maximal complement of nephrons and then loses these over time [2]. This dogma is drawn from our understanding of the development of this organ. The progenitor population during developmentThe kidney is mesodermal in origin and develops from two populations derived from intermediate mesoderm, the ureteric bud (UB) and the metanephric mesenchyme (MM). While an even broader potential had been proposed [3], genetic and lineage analyses have confirmed that the MM gives rise to all portions of the nephron other than the collecting ducts and also gives rise to elements of the renal interstitium [4][5][6]. The UB gives rise to the ureter and collecting ducts only. The MM is apparently not homogeneous but forms condensed mesenchyme around the tips of the branching UB. This cap mesenchyme (CM) contains self-renewing progenitors capable of generating all cells of the nephron other than the collecting ducts via an initial mesenchyme-epithelial transition (MET) event throughout the prenatal developmental period [6]. The continued expression of the transcription factor Six2 in CM is required for maintenance of this stem cell population during kidney development [5]. As the UB branches and extends through the MM, individual MET events occur at the underside of each tip to form a new nephron [2]. This nephron endowment therefore proceeds from the centre of the kidney out to the periphery, with the CM stem cell field remaining on the outer edge of the expanding organ. Endowment of new nephrons is restricted to prenatal development in humans, while in rodents it persists only until the imm...

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Section: Progenitors Isolated Based Upon Cellular Behaviourmentioning

confidence: 81%

Section: Progenitors Isolated Based Upon Cellular Behaviourmentioning

confidence: 99%

Stem cell options for kidney disease

Hopkins

Rae

et al. 2008

The Journal of Pathology

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“…Interestingly, the SP phenotype in rodent and human tissues often appears to be specifically determined by the expression of an ABC transporter: for example, both ABCB1 and ABCG2 transporters are highly expressed in the SP of stem cells from different tissues such as brain, bone marrow, pancreas, liver and others, all of which can be isolated based on the cells' ability to promote the efflux of the Hoechst-33342 fluorescent dye [9,[129][130][131][132][133][134][135][136][142][143][144][145][146][147][148][149][150]. Moreover, different research teams have demonstrated that ABCA3 and ABCG2 were expressed at higher levels in SP cells than in non-SP cells in human, rhesus monkey and mouse hematopoietic tissues; and microarray analysis indicated that several genes related to stem cells were substantially upregulated in the SP cells in comparison to non-SP cells [130,151,152]. This SP phenotype is present in several kinds of stem cells from different tissues, including the hematopoietic, meschenchymal, heart, liver, and pancreatic stem cells; it disappears with verapamil treatment thus indicating that the SP phenotype might result from the expression of ABC transporters in a primitive subset of stem cells in mammals [140,142,131,145,146,148,153,154].…”

Section: Abc Transporters and Stem Cellsmentioning

confidence: 99%

“…Of these, the hematopoietic stem cells (HSCs) from bone marrow can differentiate into all the different immune cells and have been routinely used to treat leukemia, lymphoma and immune deficiencies [4,5]. A certain class of HSCs from blood and bone marrow called the "side population" (SP) is described also as CD34-negative (-), c-Kit-positive (+) and Sca-1 + cells, according to their specific surface antigens [6,7]. These bone marrow repopulating SP cells are probably among the best-characterized examples of pluripotent adult stem cells to date [8,9].…”

Section: Introductionmentioning

confidence: 99%

ABC transporters, neural stem cells and neurogenesis – a different perspective

2006

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“…Contributing factors are the preferential expression of chemoresistance molecules from the ATP-binding cassette (ABC) transporter family, such as the multidrug-resistance gene 1 and the breast cancerresistance protein 1, which contribute to chemoresistance by cellular clearance of lipophilic drugs [61]. High expression of ABC-G2 has been observed in the side population (SP), which constitutes a cell population of undifferentiated cells [42,95] that efficiently exclude Hoechst 33342, representing an enriched source of stem cells [31]. Cancer cells belonging to the SP are immature, poorly differentiated, and highly tumorigenic.…”

Section: Ovarian Cancer: Pluripotency and Putative Cscsmentioning

confidence: 99%

Cancer stem cells as targets for cancer therapy: selected cancers as examples

Hombach‐Klonisch

Paranjothy

Wiecheć

et al. 2008

Arch. Immunol. Ther. Exp.

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It is becoming increasingly evident that cancer constitutes a group of diseases involving altered stem-cell maturation/differentiation and the disturbance of regenerative processes. The observed malignant transformation is merely a symptom of normal differentiation processes gone astray rather than the primary event. This review focuses on the role of cancer stem cells (CSCs) in three common but also relatively under-investigated cancers: head and neck, ovarian, and testicular cancer. For didactic purpose, the physiology of stem cells is first introduced using hematopoietic and mesenchymal stem cells as examples. This is followed by a discussion of the (possible) role of CSCs in head and neck, ovarian, and testicular cancer. Aside from basic information about the pathophysiology of these cancers, current research results focused on the discovery of molecular markers specific to these cancers are also discussed. The last part of the review is largely dedicated to signaling pathways active within various normal and CSC types (e.g. Nanog, Nestin, Notch1, Notch2, Oct3 and 4, Wnt). Different elements of these pathways are also discussed in the context

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A Side Order of Stem Cells: The SP Phenotype

Cited by 437 publications

References 72 publications

Stem cell options for kidney disease

Stem cell options for kidney disease

ABC transporters, neural stem cells and neurogenesis – a different perspective

Cancer stem cells as targets for cancer therapy: selected cancers as examples

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