scholarly journals The effect and molecular mechanism of hypoxia on proliferation and apoptosis of CD133+ renal stem cells

Author(s):  
Hong Liu ◽  
Cui Liu ◽  
Yan Qu

Congenital hydronephrosis caused by ureteropelvic junction obstruction (UPJO) eventually leads to renal interstitial fibrosis and atrophy, after a series of pathophysiological problems. Renal repair after injury depends on renal stem cells. This study aimed to determine the expression of renal stem cell marker CD133 in children of different ages and the regulatory effect of stem cell microenvironment. Renal stem cells from children of different ages were identified and screened out by flow cytometry in the study. Children with hydronephrosis were divided into neonates, infants, preschool age, school age, and adolescents groups. A hypoxic cell model prepared with CoCl2 was developed to detect the effect of hypoxia on the proliferation and apoptosis of renal stem cells. The effect and molecular mechanism of hypoxia-inducible factor 1-alpha (HIF-1α) on the proliferation and apoptosis of renal stem cells were also explored. Both hypoxia and HIF-1α significantly promoted the proliferation of renal stem cells and inhibited cell apoptosis. HIF-1α could bind to the promoter region of proliferating cell nuclear antigen (PCNA) and PROM1 (CD133) to mediate their transcription and expression. The content of CD133+ renal stem cells was the highest in the neonatal group and it decreased with the increase of age. Taken together, this study clarified the effect of age on the content of human renal stem cells and determined the regulatory mechanism of hypoxia on renal stem cells. We expect our results to provide a research basis for the treatment and clinical application of renal stem cells.

2021 ◽  
pp. ASN.2021081073
Author(s):  
Melissa Little ◽  
Benjamin Humphreys

Fifteen years ago, this journal published a review outlining future options for regenerating the kidney. At that time, stem cell populations were being identified in multiple tissues, the concept of stem cell recruitment to a site of injury was of great interest, and the possibility of postnatal renal stem cells was growing in momentum. Since that time, we have seen the advent of human induced pluripotent stem cells, substantial advances in our capacity to both sequence and edit the genome, global and spatial transcriptional analysis down to the single-cell level, and a pandemic that has challenged our delivery of health care to all. This article will look back over this period of time to see how our view of kidney development, disease, repair, and regeneration has changed and envision a future for kidney regeneration and repair over the next 15 years.


2008 ◽  
Vol 8 ◽  
pp. 1168-1176 ◽  
Author(s):  
Laren Becker ◽  
Qin Huang ◽  
Hiroshi Mashimo

Lgr5 has recently been identified as a murine marker of intestinal stem cells. Its expression has not been well characterized in human gastrointestinal tissues, but has been reported in certain cancers. With the increasing appreciation for the role of cancer stem cells or tumor-initiating cells in certain tumors, we sought to explore the expression of Lgr5 in normal and premalignant human gastrointestinal tissues. Using standard immunostaining, we compared expression of Lgr5 in normal colon and small intestine vs. small intestinal and colonic adenomas and Barrett's esophagus. In the normal tissue, Lgr5 was expressed in the expected stem cell niche, at the base of crypts, as seen in mice. However, in premalignant lesions, Lgr5+cells were not restricted to the crypt base. Additionally, their overall numbers were increased. In colonic adenomas, Lgr5+cells were commonly found clustered at the luminal surface and rarely at the crypt base. Finally, we compared immunostaining of Lgr5 with that of CD133, a previously characterized marker for tumor-initiating cells in colon cancer, and found that they identified distinct subpopulations of cells that were in close proximity, but did not costain. Our findings suggest that (1) Lgr5 is a potential marker of intestinal stem cells in humans and (2) loss of restriction to the stem cell niche is an early event in the premalignant transformation of stem cells and may play a role in carcinogenesis.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chengguang Wu ◽  
Long Chen ◽  
Yi-zhou Huang ◽  
Yongcan Huang ◽  
Ornella Parolini ◽  
...  

Human multipotent stem cell-based therapies have shown remarkable potential in regenerative medicine and tissue engineering applications due to their abilities of self-renewal and differentiation into multiple adult cell types under appropriate conditions. Presently, human multipotent stem cells can be isolated from different sources, but variation among their basic biology can result in suboptimal selection of seed cells in preclinical and clinical research. Thus, the goal of this study was to compare the biological characteristics of multipotent stem cells isolated from human bone marrow, placental decidua basalis, and urine, respectively. First, we found that urine-derived stem cells (USCs) displayed different morphologies compared with other stem cell types. USCs and placenta decidua basalis-derived mesenchymal stem cells (PDB-MSCs) had superior proliferation ability in contrast to bone marrow-derived mesenchymal stem cells (BMSCs); these cells grew to have the highest colony-forming unit (CFU) counts. In phenotypic analysis using flow cytometry, similarity among all stem cell marker expression was found, excluding CD29 and CD105. Regarding stem cell differentiation capability, USCs were observed to have better adipogenic and endothelial abilities as well as vascularization potential compared to BMSCs and PDB-MSCs. As for osteogenic and chondrogenic induction, BMSCs were superior to all three stem cell types. Future therapeutic indications and clinical applications of BMSCs, PDB-MSCs, and USCs should be based on their characteristics, such as growth kinetics and differentiation capabilities.


2011 ◽  
Vol 23 (1) ◽  
pp. 243 ◽  
Author(s):  
S.-A. Choi ◽  
J.-H. Lee ◽  
K.-J. Kim ◽  
E.-Y. Kim ◽  
K.-S. Park ◽  
...  

Adult stem cells have the capacity to differentiate into several different cell types, although their differentiation potential is limited compared with that of embryonic stem cells. Thus, adult stem cells are regarded as an exciting source for new cell therapies. Recent observations also indicate that stem cells derived from second-trimester amniocentesis are pluripotent – capable of differentiating into multiple lineages, including representatives of all 3 embryonic germ layers. In addition, amniotic fluid stem cells can be used in the generation of disease- or patient-specific stem cells, and amniotic fluid stem cells could be an ideal source for autologous cell replacement therapy in the later life of the fetus. The aim of the present study was to investigate isolation and characterisation of human amniotic fluid-derived mesenchymal stem cells (hAFS). We successfully isolated and characterised hAFS. Amniotic fluid samples were collected in the second trimester (median gestational age: 16 weeks, range: 15–17 weeks) for prenatal diagnosis. Specimens (2 mL) were centrifuged and incubated in low-glucose DMEM supplemented with 10% FBS, 25 ng of basic fibroblast growth factor, and 10 ng of epidermal growth factor at 37°C with 5% CO2. Human amniotic fluid cell (passage 6) expression of stem cell specific markers OCT-4, SOX2, Rex1, FGF4, and NANOG was confirmed by RT-PCR. Flow cytometric analysis showed that hAFS (passage 10) were positive for CD44, CD29, CD146, STRO1, and CD90 but negative for CD19. Immunocytochemical analysis of hAFS (passage 11) also showed the expression of OCT-4, SSEA-1, CD44, CD29, CD146, STRO1, and CD90, but hAFS were negative for CD19 and CD14. In conclusion, according to the previous studies on other mammalians, hAFS are an appropriate source of pluripotent stem cells. Here, we demonstrated that hAFS have a high expression of stem cell specific marker, including embryonic stem cell marker and mesenchymal stem cell marker. Therefore, amniotic fluid may be a suitable alternative source of multipotent stem cells.


Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1485 ◽  
Author(s):  
Murielle Rémy ◽  
Francesca Ferraro ◽  
Pierre Le Salver ◽  
Sylvie Rey ◽  
Elisabeth Genot ◽  
...  

Stem cells isolated from the apical papilla of wisdom teeth (SCAPs) are an attractive model for tissue repair due to their availability, high proliferation rate and potential to differentiate in vitro towards mesodermal and neurogenic lineages. Adult stem cells, such as SCAPs, develop in stem cell niches in which the oxygen concentration [O2] is low (3–8% compared with 21% of ambient air). In this work, we evaluate the impact of low [O2] on the physiology of SCAPs isolated and processed in parallel at 21% or 3% O2 without any hyperoxic shock in ambient air during the experiment performed at 3% O2. We demonstrate that SCAPs display a higher proliferation capacity at 3% O2 than in ambient air with elevated expression levels of two cell surface antigens: the alpha-6 integrin subunit (CD49f) and the embryonic stem cell marker (SSEA4). We show that the mesodermal differentiation potential of SCAPs is conserved at early passage in both [O2], but is partly lost at late passage and low [O2], conditions in which SCAPs proliferate efficiently without any sign of apoptosis. Unexpectedly, we show that autophagic flux is active in SCAPs irrespective of [O2] and that this process remains high in cells even after prolonged exposure to 3% O2.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1677-1677
Author(s):  
Toska J. Zomorodian ◽  
Debbie Greer ◽  
Kyle Wood ◽  
Bethany Foster ◽  
Delia Demers ◽  
...  

Abstract Transplanted bone marrow donor cells with tissue specific phenotypes have been found in the brain, liver, heart, skin, lung, kidney, and gut of transplanted humans and mice. Such observations have led to the controversial hypothesis that hematopoietic stem cells (HSC) might be intrinsically plastic, and through transdifferentiation or fusion lead to the repair of damaged tissues throughout the body. Alternately, it is suggested that fusion of macrophages to the recipient cells may explain this phenomenon. We have shown recently that purified HSC are the cells responsible for GFP positive donor-derived muscle fibers in the recipient mice post bone marrow transplantation. However, further studies sorting for macrophage markers Mac-1 and F4/80 also resulted in donor-derived muscle fibers in the host. To address this discrepancy, we investigated subpopulations of Mac-1 and F4/80 positive cells, in the presence or absence of stem cell markers (Sca-1 and C-kit). We demonstrate that only the subpopulations of Mac-1 and F4/80 positive cells harboring stem cell markers, Sca-1 or c-kit, were capable of contributing to the regenerating muscle post transplantation. Furthermore, these same subpopulations demonstrated single cell High Proliferative Potential (HPP) (6–26%) in a 7 factor cytokine cocktail, compared to the Mac-1 or F4/80 cells with no stem cell markers (0%). Additionally, they demonstrated long-term engraftment in all three lineages at 1-year (average chimerism of 55% versus 0% in stem cell marker negative groups). These subpopulations were also evaluated for morphology using Hematoxylin/Eosin (H/E), Wright-Giemsa, and Nonspecific Esterase staining. In the Mac-1 and F4/80 positive groups, those negative for stem cell markers resembled differentiated cells of the myeloid origin (macrophages, granulocytes), while those with positive stem cell markers demonstrated stem cell characteristics. We did not observe any engraftability, donor-derived muscle fibers, or HPP potential for CD14 or cfms positive cells coexpressing stem cell markers, indicating that these markers are more appropriate for identifying macrophages. In conclusion, our studies demonstrate that both Mac-1 and F4/80 surface markers are present on HSC and therefore caution must be taken in the interpretation of data using these macrophage markers. It is reasonable to believe that the use of Mac-1 and/or F4/80 surface markers in a lineage depletion process may result in the loss of a subpopulation of stem cells, and other markers such as CD14 or c-fms may be more appropriate for eliminating differentiated macrophages.


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