Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman’s capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell–specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24⁺CD133⁺ PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24⁺CD133⁺ PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24⁺CD133⁺ PEC but not of CD24⁻CD133⁻ renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24⁺CD133⁺ PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.

Depletion of podocytes, common to glomerular diseases in general, plays a role in the pathogenesis of glomerulosclerosis. Whether podocyte injury in adulthood can be repaired has not been established. Here, we demonstrate that in the adult human kidney, CD133+CD24+ cells consist of a hierarchical population of progenitors that are arranged in a precise sequence within Bowman9s capsule and exhibit heterogeneous potential for differentiation and regeneration. Cells localized to the urinary pole that expressed CD133 and CD24, but not podocyte markers (CD133+CD24+PDX− cells), could regenerate both tubular cells and podocytes. In contrast, cells localized between the urinary pole and vascular pole that expressed both progenitor and podocytes markers (CD133+CD24+PDX+) could regenerate only podocytes. Finally, cells localized to the vascular pole did not exhibit progenitor markers, but displayed phenotypic features of differentiated podocytes (CD133−CD24−PDX+ cells). Injection of CD133+CD24+PDX− cells, but not CD133+CD24+PDX+ or CD133-CD24− cells, into mice with adriamycin-induced nephropathy reduced proteinuria and improved chronic glomerular damage, suggesting that CD133+CD24+PDX− cells could potentially treat glomerular disorders characterized by podocyte injury, proteinuria, and progressive glomerulosclerosis.

Recent studies implicated the existence in adult human kidney of a population of renal progenitors with the potential to regenerate glomerular as well as tubular epithelial cells and characterized by coexpression of surface markers CD133 and CD24. Here, we demonstrate that CD133+CD24+ renal progenitors can be distinguished in distinct subpopulations from normal human kidneys based on the surface expression of vascular cell adhesion molecule 1, also known as CD106. CD133+CD24+CD106+ cells were localized at the urinary pole of Bowman's capsule, while a distinct population of scattered CD133+CD24+CD106− cells was localized in the proximal tubule as well as in the distal convoluted tubule. CD133+CD24+CD106+ cells exhibited a high proliferative rate and could differentiate toward the podocyte as well as the tubular lineage. By contrast, CD133+CD24+CD106− cells showed a lower proliferative capacity and displayed a committed phenotype toward the tubular lineage. Both CD133+CD24+CD106+ and CD133+CD24+CD106− cells showed higher resistance to injurious agents in comparison to all other differentiated cells of the kidney. Once injected in SCID mice affected by acute tubular injury, both of these populations displayed the capacity to engraft within the kidney, generate novel tubular cells, and improve renal function. These properties were not shared by other tubular cells of the adult kidney. Finally, CD133+CD24+CD106− cells proliferated upon tubular injury, becoming the predominating part of the regenerating epithelium in patients with acute or chronic tubular damage. These data suggest that CD133+CD24+CD106− cells represent tubular‐committed progenitors that display resistance to apoptotic stimuli and exert regenerative potential for injured tubular tissue. STEM CELLS2012;30:1714–1725

Objective: To summarise and meta‐analyse current literature on metabolic syndrome ( MetS ) and benign prostatic enlargement ( BPE ), focusing on all the components of MetS and their relationship with prostate volume, transitional zone volume, prostate‐specific antigen and urinary symptoms, as evidence suggests an association between MetS and lower urinary tract symptoms ( LUTS ) due to BPE . Methods: An extensive P ub M ed and S copus search was performed including the following keywords: ‘metabolic syndrome’, ‘diabetes’, ‘hypertension’, ‘obesity’ and ‘dyslipidaemia’ combined with ‘lower urinary tract symptoms’, ‘benign prostatic enlargement’, ‘benign prostatic hyperplasia’ and ‘prostate’. Results: Of the retrieved articles, 82 were selected for detailed evaluation, and eight were included in this review. The eight studies enrolled 5403 patients, of which 1426 (26.4%) had MetS defined according to current classification. Patients with MetS had significantly higher total prostate volume when compared with those without MetS (+1.8 mL, 95% confidence interval [ CI ] 0.74–2.87; P < 0.001). Conversely, there were no differences between patients with or without MetS for International Prostate Symptom Score total or LUTS subdomain scores. Meta‐regression analysis showed that differences in total prostate volume were significantly higher in older (adjusted r = 0.09; P = 0.02), obese patients (adjusted r = 0.26; P < 0.005) and low serum high‐density lipoprotein cholesterol concentrations (adjusted r = −0.33; P < 0.001). Conclusions: Our results underline the exacerbating role of MetS ‐induced metabolic derangements in the development of BPE . Obese, dyslipidaemic, and aged men have a higher risk of having MetS as a determinant of their prostate enlargement.

Recently, we have identified a population of renal progenitor cells in human kidneys showing regenerative potential for injured renal tissue of SCID mice. We demonstrate here that among all known chemokine receptors, human renal progenitor cells exhibit high expression of both stromal-derived factor-1 (SDF-1) receptors, CXCR4 and CXCR7. In SCID mice with acute renal failure (ARF), SDF-1 was strongly up-regulated in resident cells surrounding necrotic areas. In the same mice, intravenously injected renal stem/progenitor cells engrafted into injured renal tissue decreased the severity of ARF and prevented renal fibrosis. These beneficial effects were abolished by blocking either CXCR4 or CXCR7, which dramatically reduced the number of engrafting renal progenitor cells. However, although SDF-1–induced migration of renal progenitor cells was only abolished by an anti-CXCR4 antibody, transendothelial migration required the activity of both CXCR4 and CXCR7, with CXCR7 being essential for renal progenitor cell adhesion to endothelial cells. Moreover, CXCR7 but not CXCR4 was responsible for the SDF-1–induced renal progenitor cell survival. Collectively, these findings suggest that CXCR4 and CXCR7 play an essential, but differential, role in the therapeutic homing of human renal progenitor cells in ARF, with important implications for the development of stem cell–based therapies.