Isolation and Characterization of Multipotent Progenitor Cells from the Bowman’s Capsule of Adult Human Kidneys

Sagrinati, Costanza; Netti, Giuseppe Stefano; Mazzinghi, Benedetta; Lazzeri, Elena; Liotta, Francesco; Frosali, Francesca; Ronconi, Elisa; Meini, Claudia; Gacci, Mauro; Squecco, Roberta; Carini, Marco; Gesualdo, Loreto; Francini, Fabio; Maggi, Enrico; Annunziato, Francesco; Lasagni, Laura; Serio, Mario; Romagnani, Sergio; Romagnani, Paola

doi:10.1681/asn.2006010089

Cited by 664 publications

(682 citation statements)

References 51 publications

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“…The expression of CD133 in haematopoietic stem cells, endothelial progenitor cells and glioblastomas suggests that this marker alone is likely to isolate a heterogeneous population containing interstitial as well as epithelial cells, as indicated by another group [81]. In human adult kidneys, a subset of parietal epithelial cells localized to the urinary pole of the Bowman's capsule was identified, based on co-expression of CD24 and CD133 [81]. They referred to these as adult parietal epithelial multipotent progenitors (APEMPs).…”

Section: Progenitors Isolated Based Upon Specific Marker Expressionmentioning

confidence: 89%

“…Of note, in the heart Camargo et al [37] have [39] Glycerol-induced ARF (mouse) MSCs Enhanced tubular proliferation [68] IR (rat) Papilla LRCs Proliferation and incorporation [149] IR (mouse) Bone marrow No functional improvement, intrarenal cells are the main source of repopulating cell during repair [22] Folic acid-induced acute tubular injury (mouse) Bone marrow Intrinsic tubular cell proliferation accounts for repair after damage [150] Folic acid-induced acute tubular injury (mouse) Bone marrow 10% incorporation in tubules and G-CSF doubles this rate [151] IR (rat) MSCs Improved renal function and less injury [152] Cisplatin-induced renal failure (mouse) MSCs Accelerated tubular proliferation [153] UUO (mouse) Bone marrow macrophages Reduced renal fibrosis [41] IR (rat) MSCs Improved renal function, increased proliferation and decreased apoptosis [84] IR (rat) rKS56 (S3 segment outgrowth) Replace tubular and improve function [80] Glycerol-induced tubulonecrosis (mouse) Human CD133 + cells Homing and tubular integration [66] UUO (rat) Label-retaining cells (LRC) Proliferates, migrates and transdifferentiates into fibroblast-like cells [27] Cisplatin-induced renal failure (mouse) G-CSF ± M-CSF Improvement in renal function and prevention of renal tubular injury [154] Anti-Thy1.1 GN (rat) MSCs Increased glomerular proliferation and reduction in proteinuria [53] Col4α3 deficiency (mouse) MSCs Prevented loss of peritubular capillaries and reduced fibrosis but no increase in function or survival [24] Col4α3 deficiency (mouse) Bone marrow Partial restoration of expression of the type IV collagen α3 chain, improved histology and function [25] Col4α3 deficiency (mouse) MSCs Improved function and glomerular scarring and interstitial fibrosis reduced [155] UUO (mouse) BM Instertitial BM-derived cells do not contribute significantly to collagen synthesis after damage [74] Adriamycin-nephropathy (mouse) Renal side population Functional amprovement but very low rate of engraftment. [78] IR (rat) Multipotent renal progenitor cells In vivo epithelial differentiation, no difference on renal function [67] Cultured metanephroi (rat) LRCs Integration [81] Glycerol injection (mouse) Human CD24 + CD133+ Tubular regeneration and function improvement [83] IR (mouse) Mice Sca-1 + cells Adopt tubular phenotype …”

Section: Bone Marrow-derived Cellsmentioning

confidence: 99%

“…Using antibodies to the endothelial progenitor cell marker, CD133, they isolated cells based on the presence of CD133 and absence of haematopoietic markers and demonstrated in vitro that these cells were multipotent, able to express markers of epithelium and were capable of expansion. The expression of CD133 in haematopoietic stem cells, endothelial progenitor cells and glioblastomas suggests that this marker alone is likely to isolate a heterogeneous population containing interstitial as well as epithelial cells, as indicated by another group [81]. In human adult kidneys, a subset of parietal epithelial cells localized to the urinary pole of the Bowman's capsule was identified, based on co-expression of CD24 and CD133 [81].…”

Section: Progenitors Isolated Based Upon Specific Marker Expressionmentioning

confidence: 99%

“…While the location of putative stem/progenitor cells has been described in some studies [68,81], the isolation of stem/progenitor activity based upon location is less common. Kitamura et al [84] published a report in which the isolation of potential renal stem/progenitor cells based on sub-compartmental dissection of the adult kidney was performed.…”

Section: Progenitors Isolated Based On Locationmentioning

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 Specific Marker Expressionmentioning

confidence: 89%

Section: Bone Marrow-derived Cellsmentioning

confidence: 99%

Section: Progenitors Isolated Based Upon Specific Marker Expressionmentioning

confidence: 99%

Section: Progenitors Isolated Based On Locationmentioning

confidence: 99%

See 2 more Smart Citations

Stem cell options for kidney disease

Hopkins

Rae

et al. 2008

The Journal of Pathology

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“…These results cannot simply be explained through the protective effects of angiotensin converting enzyme inhibitors on podocyte loss, but rather suggest that novel podocytes can potentially be generated. Recently, it was demonstrated that a population of progenitor cells in the parietal epithelium of the Bowman’s capsule of adult human kidney acts as a source of intra-renal progenitors for podocytes [105, 106]. These cells follow a phenotypical and functional hierarchy within the parietal epithelium of Bowman’s capsule.…”

Section: A Lifeboat For the Glomerulus: The Renal Progenitor Cellsmentioning

confidence: 99%

Podocyte Mitosis – A Catastrophe

Lasagni

Lazzeri²,

Shankland

et al. 2012

CMM

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Podocyte loss plays a key role in the progression of glomerular disorders towards glomerulosclerosis and chronic kidney disease. Podocytes form unique cytoplasmic extensions, foot processes, which attach to the outer surface of the glomerular basement membrane and interdigitate with neighboring podocytes to form the slit diaphragm. Maintaining these sophisticated structural elements requires an intricate actin cytoskeleton. Genetic, mechanic, and immunologic or toxic forms of podocyte injury can cause podocyte loss, which causes glomerular filtration barrier dysfunction, leading to proteinuria. Cell migration and cell division are two processes that require a rearrangement of the actin cytoskeleton; this rearrangement would disrupt the podocyte foot processes, therefore, podocytes have a limited capacity to divide or migrate. Indeed, all cells need to rearrange their actin cytoskeleton to assemble a correct mitotic spindle and to complete mitosis. Podocytes, even when being forced to bypass cell cycle checkpoints to initiate DNA synthesis and chromosome segregation, cannot complete cytokinesis efficiently and thus usually generate aneuploid podocytes. Such aneuploid podocytes rapidly detach and die, a process referred to as mitotic catastrophe. Thus, detached or dead podocytes cannot be adequately replaced by the proliferation of adjacent podocytes. However, even glomerular disorders with severe podocyte injury can undergo regression and remission, suggesting alternative mechanisms to compensate for podocyte loss, such as podocyte hypertrophy or podocyte regeneration from resident renal progenitor cells. Together, mitosis of the terminally differentiated podocyte rather accelerates podocyte loss and therefore glomerulosclerosis. Finding ways to enhance podocyte regeneration from other sources remains a challenge goal to improve the treatment of chronic kidney disease in the future.

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Regeneration of Vertebrate Tissues: Model Systems

Stocum

2015

Encyclopedia of Life Sciences

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Vertebrate animals exhibit four mechanisms of tissue regeneration: re‐growth of cellular parts, such as nerve axons; lineage‐specific proliferation of differentiated cells with or without dedifferentiation; transdifferentiation and activation of adult stem cells. The most common mechanism is the proliferation and differentiation of adult stem cells, used by epithelia, muscle, bone and blood. In some cases, such as the liver and pancreas, regeneration is accomplished by either lineage‐specific proliferation of differentiated cells or a stem cell population, depending on the nature of the damage. All four mechanisms are used by urodele salamanders in the regeneration of limbs. The cellular activities in all these mechanisms are regulated by a wide variety of growth factor signalling pathways and transcription factors. Regenerative medicine uses three major strategies based on knowledge of regenerative mechanisms: transplants of stem cells or their derivatives, construction of bioartificial tissues composed of natural or synthetic biomaterials seeded with cells and the pharmaceutical induction of regeneration at the site of injury by natural or synthetic regeneration‐promoting molecules. Key Concepts Regeneration restores the original structure and function of damaged or missing tissues. Tissues use four mechanisms to regenerate: re‐growth of cell parts, lineage‐specific reproduction of parent cells, transdifferentiation and activation of adult stem cells. Some tissues use more than one mechanism of regeneration. Growth factor signals and transcription factors are important regulators of regeneration. Regenerative medicine uses three strategies to regenerate damaged tissues: cell transplants, bioartificial tissue implants and pharmaceutical induction of regeneration directly at the site of damage by scaffolds or soluble molecules. The source of cells for transplants and bioartificial tissues is a crucial issue for regenerative medicine. Induced pluripotent stem cells (iPSCs) and/or transdifferentiation may solve many of the problems presented by adult and embryonic stem cells.

show abstract

Isolation and Characterization of Multipotent Progenitor Cells from the Bowman’s Capsule of Adult Human Kidneys

Cited by 664 publications

References 51 publications

Stem cell options for kidney disease

Stem cell options for kidney disease

Podocyte Mitosis – A Catastrophe

Regeneration of Vertebrate Tissues: Model Systems

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