scholarly journals Essential but differential role for CXCR4 and CXCR7 in the therapeutic homingof human renal progenitor cells

2008 ◽  
Vol 205 (2) ◽  
pp. 479-490 ◽  
Author(s):  
Benedetta Mazzinghi ◽  
Elisa Ronconi ◽  
Elena Lazzeri ◽  
Costanza Sagrinati ◽  
Lara Ballerini ◽  
...  

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.

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Lisa Nguyen ◽  
Lucas-Sebastian Spitzhorn ◽  
James Adjaye

Urine has become the source of choice for noninvasive renal epithelial cells and renal stem cells which can be used for generating induced pluripotent stem cells. The aim of this study was to generate a 3D nephrogenic progenitor cell model composed of three distinct cell types—urine-derived SIX2-positive renal progenitor cells, iPSC-derived mesenchymal stem cells, and iPSC-derived endothelial cells originating from the same individual. Characterization of the generated mesenchymal stem cells revealed plastic adherent growth and a trilineage differentiation potential to adipocytes, chondrocytes, and osteoblasts. Furthermore, these cells express the typical MSC markers CD73, CD90, and CD105. The induced endothelial cells express the endothelial cell surface marker CD31. Upon combination of urine-derived renal progenitor cells, induced mesenchymal stem cells, and induced endothelial cells at a set ratio, the cells self-condensed into three-dimensional nephrogenic progenitor cells which we refer to as 3D-NPCs. Immunofluorescence-based stainings of sectioned 3D-NPCs revealed cells expressing the renal progenitor cell markers (SIX2 and PAX8), podocyte markers (Nephrin and Podocin), the endothelial marker (CD31), and mesenchymal markers (Vimentin and PDGFR-β). These 3D-NPCs share kidney progenitor characteristics and thus the potential to differentiate into podocytes and proximal and distal tubules. As urine-derived renal progenitor cells can be easily obtained from cells shed into urine, the generation of 3D-NPCs directly from renal progenitor cells instead of pluripotent stem cells or kidney biopsies holds a great potential for the use in nephrotoxicity tests, drug screening, modelling nephrogenesis and diseases.


2019 ◽  
Vol 30 (12) ◽  
pp. 2293-2305 ◽  
Author(s):  
Shuichiro Yamanaka ◽  
Yatsumu Saito ◽  
Toshinari Fujimoto ◽  
Tsuyoshi Takamura ◽  
Susumu Tajiri ◽  
...  

BackgroundThe limited availability of donor kidneys for transplantation has spurred interest in investigating alternative strategies, such as regenerating organs from stem cells transplanted into animal embryos. However, there is no known method for transplanting cells into later-stage embryos, which may be the most suitable host stages for organogenesis, particularly into regions useful for kidney regeneration.MethodsWe demonstrated accurate transplantation of renal progenitor cells expressing green fluorescent protein to the fetal kidney development area by incising the opaque uterine muscle layer but not the transparent amniotic membrane. We allowed renal progenitor cell–transplanted fetuses to develop for 6 days postoperatively before removal for analysis. We also transplanted renal progenitor cells into conditional kidney-deficient mouse embryos. We determined growth and differentiation of transplanted cells in all cases.ResultsRenal progenitor cell transplantation into the retroperitoneal cavity of fetuses at E13–E14 produced transplant-derived, vascularized glomeruli with filtration function and did not affect fetal growth or survival. Cells transplanted to the nephrogenic zone produced a chimera in the cap mesenchyme of donor and host nephron progenitor cells. Renal progenitor cells transplanted to conditional kidney-deficient fetuses induced the formation of a new nephron in the fetus that is connected to the host ureteric bud.ConclusionsWe developed a cell transplantation method for midstage to late-stage fetuses. In vivo kidney regeneration from renal progenitor cells using the renal developmental environment of the fetus shows promise. Our findings suggest that fetal transplantation methods may contribute to organ regeneration and developmental research.


2021 ◽  
pp. 101699
Author(s):  
Chih-Yang Hsu ◽  
Pei-Ling Chi ◽  
Hsin-Yu Chen ◽  
Shih-Hsiang Ou ◽  
Kang-Ju Chou ◽  
...  

Development ◽  
2014 ◽  
Vol 141 (5) ◽  
pp. 1047-1058 ◽  
Author(s):  
J. M. Basta ◽  
L. Robbins ◽  
S. M. Kiefer ◽  
D. Dorsett ◽  
M. Rauchman

2013 ◽  
Vol 49 (3) ◽  
pp. 235-247
Author(s):  
Hayam Abdel Meguid El Aggan ◽  
Mona Abdel Kader Salem ◽  
Nahla Mohamed Gamal Farahat ◽  
Ahmad Fathy El-Koraie ◽  
Ghaly Abd Al-Rahim Mohammed Kotb

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e68296 ◽  
Author(s):  
Fabio Sallustio ◽  
Grazia Serino ◽  
Vincenzo Costantino ◽  
Claudia Curci ◽  
Sharon N. Cox ◽  
...  

2013 ◽  
Vol 29 (4) ◽  
pp. 665-672 ◽  
Author(s):  
Paul J. D. Winyard ◽  
Karen L. Price

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Elís Rosélia Dutra de Freitas Siqueira Silva ◽  
Napoleão Martins Argôlo Neto ◽  
Dayseanny de Oliveira Bezerra ◽  
Sandra Maria Mendes de Moura Dantas ◽  
Lucilene dos Santos Silva ◽  
...  

In vitro senescence of multipotent cells has been commonly associated with DNA damage induced by oxidative stress. These changes may vary according to the sources of production and the studied lineages, which raises questions about the effect of growing time on genetic stability. This study is aimed at evaluating the evolution of genetic stability, viability, and oxidative stress of bone marrow mesenchymal stem cells (MSCBMsu) and renal progenitor cells of the renal cortex (RPCsu) of swine (Sus scrofa domesticus) in culture passages. P2, P5, and P9 were used for MSCBMsu and P1, P2, and P3 for RPCsu obtained by thawing. The experimental groups were submitted to MTT, apoptosis and necrosis assays, comet test, and reactive substance measurements of thiobarbituric acid (TBARS), nitrite, reduced glutathione (GSH), and catalase. The MTT test curve showed a mean viability of 1.14±0.62 and 1.12±0.54, respectively, for MSCBMsu and RPCsu. The percentages of MSCBMsu and RPCsu were presented, respectively, for apoptosis, an irregular and descending behavior, and necrosis, ascending and irregular. The DNA damage index showed higher intensity among the MSCBMsu in the P5 and P9 passages (p<0.05). In the TBARS evaluation, there was variation among the lines of RPCsu and MSCBMsu, presenting the last most significant variations (p<0.05). In the nitrite values, we identified only among the lines, in the passages P1 and P2, with the highest averages displayed by the MSCBMsu lineage (p<0.05). The measurement of antioxidant system activity showed high standards, identifying differences only for GSH values, in the RPCsu lineage, in P3 (p<0.05). This study suggests that the maintenance of cell culture in the long term induces lower regulation of oxidative stress, and RPCsu presents higher genetic stability and lower oxidative stress than MSCBMsu during in vitro expansion.


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