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  • 1
    Language: English
    In: PloS one, 2008-05-21, Vol.3 (5), p.e2213-e2213
    Description: Mesenchymal stem cells (MSC) comprise a promising tool for cellular therapy. These cells are usually culture expanded prior to their application. However, a precise molecular definition of MSC and the sequel of long-term in vitro culture are yet unknown. In this study, we have addressed the impact of replicative senescence on human MSC preparations. Within 43 to 77 days of cultivation (7 to 12 passages), MSC demonstrated morphological abnormalities, enlargement, attenuated expression of specific surface markers, and ultimately proliferation arrest. Adipogenic differentiation potential decreased whereas the propensity for osteogenic differentiation increased. mRNA expression profiling revealed a consistent pattern of alterations in the global gene expression signature of MSC at different passages. These changes are not restricted to later passages, but are continuously acquired with increasing passages. Genes involved in cell cycle, DNA replication and DNA repair are significantly down-regulated in late passages. Genes from chromosome 4q21 were over-represented among differentially regulated transcripts. Differential expression of 10 genes has been verified in independent donor samples as well as in MSC that were isolated under different culture conditions. Furthermore, miRNA expression profiling revealed an up-regulation of hsa-mir-371, hsa-mir-369-5P, hsa-mir-29c, hsa-mir-499 and hsa-let-7f upon in vitro propagation. Our studies indicate that replicative senescence of MSC preparations is a continuous process starting from the first passage onwards. This process includes far reaching alterations in phenotype, differentiation potential, global gene expression patterns, and miRNA profiles that need to be considered for therapeutic application of MSC preparations.
    Subject(s): Abnormalities ; Adipocytes - chemistry ; Aging ; Antigens ; Biocompatibility ; Biomedical materials ; Bone Marrow and Stem Cell Transplantation ; Cell Biology ; Cell culture ; Cell cycle ; Cell Differentiation ; Cell Division ; Cellular Senescence ; Chromosome 4 ; Cultivation ; Cyclin-dependent kinases ; Deoxyribonucleic acid ; Developmental Biology ; Differentiation ; DNA ; DNA biosynthesis ; DNA methylation ; DNA repair ; DNA Repair - genetics ; DNA replication ; DNA Replication - genetics ; Enlargement ; Epigenetics ; Gene Expression ; Gene Expression Profiling ; Genes ; Genetics and Genomics ; Genomics ; Hematology ; Humans ; Immunology ; Kinases ; Laboratories ; Localization ; Lung cancer ; Medicine ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - metabolism ; Mesenchyme ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; miRNA ; Molecular biology ; Morphology ; Pediatrics ; Population ; Profiling ; Propagation ; Quality control ; Ribonucleic acid ; RNA ; Senescence ; Stem Cells ; Surface markers ; Transplantation
    ISSN: 1932-6203
    E-ISSN: 1932-6203
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 2
    Language: English
    In: Scientific reports, 2021-01-22, Vol.11 (1), p.2128-2128
    Description: SHANK2 mutations have been identified in individuals with neurodevelopmental disorders, including intellectual disability and autism spectrum disorders (ASD). Using CRISPR/Cas9 genome editing, we obtained SH-SY5Y cell lines with frameshift mutations on one or both SHANK2 alleles. We investigated the effects of the different SHANK2 mutations on cell morphology, cell proliferation and differentiation potential during early neuronal differentiation. All mutant cell lines showed impaired neuronal differentiation marker expression. Cells with bi-allelic SHANK2 mutations revealed diminished apoptosis and increased proliferation, as well as decreased neurite outgrowth during early neuronal differentiation. Bi-allelic SHANK2 mutations resulted in an increase in p-AKT levels, suggesting that SHANK2 mutations impair downstream signaling of tyrosine kinase receptors. Additionally, cells with bi-allelic SHANK2 mutations had lower amyloid precursor protein (APP) expression compared to controls, suggesting a molecular link between SHANK2 and APP. Together, we can show that frameshift mutations on one or both SHANK2 alleles lead to an alteration of neuronal differentiation in SH-SY5Y cells, characterized by changes in cell growth and pre- and postsynaptic protein expression. We also provide first evidence that downstream signaling of tyrosine kinase receptors and amyloid precursor protein expression are affected.
    Subject(s): AKT protein ; Alleles ; Alzheimer's disease ; Amyloid precursor protein ; Apoptosis ; Autism ; Axonogenesis ; Cell differentiation ; Cell growth ; Cell lines ; Cell proliferation ; CRISPR ; Cytology ; Frameshift mutation ; Genomes ; Intellectual disabilities ; Kinases ; Mutation ; Neurodevelopmental disorders ; Protein expression ; Protein-tyrosine kinase ; Proteins ; Tyrosine
    E-ISSN: 2045-2322
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
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  • 3
    Language: English
    In: PloS one, 2009-06-09, Vol.4 (6), p.e5846-e5846
    Description: The regenerative potential diminishes with age and this has been ascribed to functional impairments of adult stem cells. Cells in culture undergo senescence after a certain number of cell divisions whereby the cells enlarge and finally stop proliferation. This observation of replicative senescence has been extrapolated to somatic stem cells in vivo and might reflect the aging process of the whole organism. In this study we have analyzed the effect of aging on gene expression profiles of human mesenchymal stromal cells (MSC) and human hematopoietic progenitor cells (HPC). MSC were isolated from bone marrow of donors between 21 and 92 years old. 67 genes were age-induced and 60 were age-repressed. HPC were isolated from cord blood or from mobilized peripheral blood of donors between 27 and 73 years and 432 genes were age-induced and 495 were age-repressed. The overlap of age-associated differential gene expression in HPC and MSC was moderate. However, it was striking that several age-related gene expression changes in both MSC and HPC were also differentially expressed upon replicative senescence of MSC in vitro. Especially genes involved in genomic integrity and regulation of transcription were age-repressed. Although telomerase activity and telomere length varied in HPC particularly from older donors, an age-dependent decline was not significant arguing against telomere exhaustion as being causal for the aging phenotype. These studies have demonstrated that aging causes gene expression changes in human MSC and HPC that vary between the two different cell types. Changes upon aging of MSC and HPC are related to those of replicative senescence of MSC in vitro and this indicates that our stem and progenitor cells undergo a similar process also in vivo.
    Subject(s): Adult ; Age ; Age Factors ; Aged ; Aged, 80 and over ; Aging ; Aging (artificial) ; Antigens ; Bioinformatics ; Blood ; Bone marrow ; Bone Marrow and Stem Cell Transplantation ; Bone Marrow Cells - cytology ; Bone marrow transplantation ; Cell Biology ; Cell culture ; Cell division ; Cell proliferation ; Cells (biology) ; Cellular Senescence ; Cord blood ; Developmental Biology ; Exhaustion ; Female ; Gene Expression ; Gene regulation ; Genes ; Genetic transcription ; Genomes ; Genomics ; Hematology ; Hematopoietic Stem Cells - cytology ; Hemopoiesis ; Humanities ; Humans ; Immunophenotyping - methods ; Laboratories ; Localization ; Male ; Medicine ; Mesenchyme ; Middle Aged ; Molecular biology ; Oligonucleotide Array Sequence Analysis ; Peripheral blood ; Phenotype ; Population ; Rodents ; Senescence ; Skin ; Stem Cells ; Stem Cells - cytology ; Stromal cells ; Telomerase ; Telomeres ; Transcription ; Umbilical cord
    ISSN: 1932-6203
    E-ISSN: 1932-6203
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 4
    Language: English
    In: International journal of cancer, 2021-06-01, Vol.148 (11), p.2825-2838
    Description: To acquire a better understanding of clonal evolution of acute myeloid leukemia (AML) and to identify the clone(s) responsible for disease recurrence, we have comparatively studied leukemia‐specific mutations by whole‐exome‐sequencing (WES) of both the leukemia and the nonleukemia compartments derived from the bone marrow of AML patients. The T‐lymphocytes, B‐lymphocytes and the functionally normal hematopoietic stem cells (HSC), that is, CD34+/CD38−/ALDH+ cells for AML with rare‐ALDH+ blasts (〈1.9% ALDH+ cells) were defined as the nonleukemia compartments. WES identified 62 point‐mutations in the leukemia compartment derived from 12 AML‐patients at the time of diagnosis and 73 mutations in 3 matched relapse cases. Most patients (8/12) showed 4 to 6 point‐mutations per sample at diagnosis. Other than the mutations in the recurrently mutated genes such as DNMT3A, NRAS and KIT, we were able to identify novel point‐mutations that have not yet been described in AML. Some leukemia‐specific mutations and cytogenetic abnormalities including DNMT3A(R882H), EZH2(I146T) and inversion(16) were also detectable in the respective T‐lymphocytes, B‐lymphocytes and HSC in 5/12 patients, suggesting that preleukemia HSC might represent the source of leukemogenesis for these cases. The leukemic evolution was reconstructed for five cases with detectable preleukemia clones, which were tracked in follow‐up and relapse samples. Four of the five patients with detectable preleukemic mutations developed relapse. The presence of leukemia‐specific mutations in these nonleukemia compartments, especially after chemotherapy or after allogeneic stem cell transplantation, is highly relevant, as these could be responsible for relapse. This discovery may facilitate the identification of novel targets for long‐term cure. What's new? Acute myeloid leukemia (AML) develops and progresses through a multistep process, involving the accumulation of multiple molecular abnormalities over time. Little is known, however, about AML‐inducing mutations and the role of clones in AML evolution and prognosis. Here, using molecular comparison of leukemic and non‐leukemic cells derived from the same bone marrow of AML patients, the authors identified novel point mutations and initiating mutations in AML. Moreover, leukemic evolution was reconstructed from pre‐leukemic clones in five patients, four of whom experienced relapse. The findings provide insight into clonal evolution in AML and could aid the identification of novel therapeutic targets.
    Subject(s): acute myeloid leukemia (AML) ; Analysis ; Antimitotic agents ; Antineoplastic agents ; Cancer ; Cancer and Oncology ; Cancer och onkologi ; Chemotherapy ; Clinical Medicine ; clonal evolution ; Cloning ; Diseases ; Evolution ; Gene mutations ; Hematopoietic stem cells ; hematopoietic stem cells (HSC) ; Klinisk medicin ; Lymphocytes ; Medical and Health Sciences ; Medical research ; Medicin och hälsovetenskap ; Medicine, Experimental ; Methyltransferases ; Relapse ; Stem cells ; Transplantation
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
    Source: SWEPUB Freely available online
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  • 5
    Language: English
    In: Journal of cellular and molecular medicine, 2010-01, Vol.14 (1‐2), p.337-350
    Description: Mesenchymal stromal cells (MSC) have been suggested to provide a suitable cellular environment for in vitro expansion of haematopoietic stem and progenitor cells (HPC) from umbilical cord blood. In this study, we have simultaneously analysed the cell division history and immunophenotypic differentiation of HPC by using cell division tracking with carboxyfluorescein diacetate N‐succinimidyl ester (CFSE). Co‐culture with MSC greatly enhanced proliferation of human HPC, especially of the more primitive CD34+CD38− fraction. Without co‐culture CD34 and CD133 expressions decreased after several cell divisions, whereas CD38 expression was up‐regulated after some cell divisions and then diminished in fast proliferating cells. Co‐culture with MSC maintained a primitive immunophenotype (CD34+, CD133+ and CD38−) for more population doublings, whereas up‐regulation of differentiation markers (CD13, CD45 and CD56) in HPC was delayed to higher numbers of cell divisions. Especially MSC of early cell passages maintained CD34 expression in HPC over more cell divisions, whereas MSC of higher passages further enhanced their proliferation rate. Inhibition of mitogen‐activated protein kinase 1 (MAPK1) impaired proliferation and differentiation of HPC, but not maintenance of long‐term culture initiating cells. siRNA knockdown of N‐cadherin and VCAM1 in feeder layer cells increased the fraction of slow dividing HPC, whereas knockdown of integrin beta 1 (ITGB1) and CD44 impaired their differentiation. In conclusion, MSC support proliferation as well as self‐renewal of HPC with primitive immunophenotype. The use of early passages of MSC and genetic manipulation of proteins involved in HPC–MSC interaction might further enhance cord blood expansion on MSC.
    Subject(s): adhesion proteins ; ADP-ribosyl Cyclase 1 - metabolism ; Antigens, CD34 - metabolism ; Cell Adhesion Molecules - genetics ; Cell Adhesion Molecules - metabolism ; Cell Culture Techniques ; Cell Differentiation - physiology ; Cell division ; Cell Proliferation ; Cells, Cultured ; Cellular Senescence - physiology ; co-culture ; Coculture Techniques ; cord blood ; Fetal Blood - cytology ; Genetics ; Genotype & phenotype ; haematopoietic stem cells ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - physiology ; Humans ; immunophenotype ; Immunophenotyping ; Kinases ; mesenchymal stromal cells ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - physiology ; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors ; Mitogen-Activated Protein Kinase 1 - genetics ; Mitogen-Activated Protein Kinase 1 - metabolism ; proliferation ; Proteins ; replicative senescence ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; stem cell niche ; Stromal Cells - cytology ; Stromal Cells - physiology ; Studies
    ISSN: 1582-1838
    E-ISSN: 1582-4934
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 6
    Language: English
    In: Nature communications, 2018-10-01, Vol.9 (1), p.4004-4004
    Description: Diminishing potential to replace damaged tissues is a hallmark for ageing of somatic stem cells, but the mechanisms remain elusive. Here, we present proteome-wide atlases of age-associated alterations in human haematopoietic stem and progenitor cells (HPCs) and five other cell populations that constitute the bone marrow niche. For each, the abundance of a large fraction of the ~12,000 proteins identified is assessed in 59 human subjects from different ages. As the HPCs become older, pathways in central carbon metabolism exhibit features reminiscent of the Warburg effect, where glycolytic intermediates are rerouted towards anabolism. Simultaneously, altered abundance of early regulators of HPC differentiation reveals a reduced functionality and a bias towards myeloid differentiation. Ageing causes alterations in the bone marrow niche too, and diminishes the functionality of the pathways involved in HPC homing. The data represent a valuable resource for further analyses, and for validation of knowledge gained from animal models.
    Subject(s): Adult ; Adult Stem Cells - cytology ; Aging - genetics ; Aging - metabolism ; Aging - pathology ; Bone Marrow Cells - cytology ; Bone Marrow Cells - metabolism ; Carbon - metabolism ; Cellular Senescence - genetics ; Female ; Gene Expression Profiling ; Glycolysis ; Hematopoiesis ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - metabolism ; Humans ; Male ; Middle Aged ; Proteome ; Stem Cell Niche ; Young Adult
    ISSN: 2041-1723
    E-ISSN: 2041-1723
    Source: Nature Open Access
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 7
    Language: English
    In: Scientific reports, 2020-07-14, Vol.10 (1), p.11597-11597
    Description: Inspired by recent proteomic data demonstrating the upregulation of carbon and glycogen metabolism in aging human hematopoietic stem and progenitor cells (HPCs, CD34+ cells), this report addresses whether this is caused by elevated glycolysis of the HPCs on a per cell basis, or by a subpopulation that has become more glycolytic. The average glycogen content in individual CD34+ cells from older subjects (〉 50 years) was 3.5 times higher and more heterogeneous compared to younger subjects (〈 35 years). Representative glycolytic enzyme activities in HPCs confirmed a significant increase in glycolysis in older subjects. The HPCs from older subjects can be fractionated into three distinct subsets with high, intermediate, and low glucose uptake (GU) capacity, while the subset with a high GU capacity could scarcely be detected in younger subjects. Thus, we conclude that upregulated glycolysis in aging HPCs is caused by the expansion of a more glycolytic HPC subset. Since single-cell RNA analysis has also demonstrated that this subpopulation is linked to myeloid differentiation and increased proliferation, isolation and mechanistic characterization of this subpopulation can be utilized to elucidate specific targets for therapeutic interventions to restore the lineage balance of aging HPCs.
    Subject(s): Adult ; Aging ; Carbon - metabolism ; CD34 antigen ; Cellular Senescence - genetics ; Enzymatic activity ; Female ; Glycogen ; Glycogen - metabolism ; Glycolysis ; Hematopoietic Stem Cells - metabolism ; Hemopoiesis ; Humans ; Male ; Metabolism ; Middle Aged ; Progenitor cells ; Ribonucleic acid--RNA ; Stem Cells - metabolism ; Therapeutic applications
    ISSN: 2045-2322
    E-ISSN: 2045-2322
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
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  • 8
    Language: English
    In: International journal of cancer, 2015-08-01, Vol.137 (3), p.525-536
    Description: To understand the precise disease driving mechanisms in acute myeloid leukemia (AML), comparison of patient matched hematopoietic stem cells (HSC) and leukemia stem cells (LSC) is essential. In this analysis, we have examined the value of aldehyde dehydrogenase (ALDH) activity in combination with CD34 expression for the separation of HSC from LSC in 104 patients with de novo AML. The majority of AML patients (80 out of 104) had low percentages of cells with high ALDH activity (ALDH+ cells; 〈1.9%; ALDH‐rare AML), whereas 24 patients had relatively numerous ALDH+ cells (≥1.9%; ALDH‐numerous AML). In patients with ALDH‐rare AML, normal HSC could be separated by their CD34+ALDH+ phenotype, whereas LSC were exclusively detected among CD34+ALDH− cells. For patients with ALDH‐numerous AML, the CD34+ALDH+ subset consisted mainly of LSC and separation from HSC was not feasible. Functional analyses further showed that ALDH+ cells from ALDH‐numerous AML were quiescent, refractory to ARA‐C treatment and capable of leukemic engraftment in a xenogenic mouse transplantation model. Clinically, resistance to chemotherapy and poor long‐term outcome were also characteristic for patients with ALDH‐numerous AML providing an additional risk‐stratification tool. The difference in spectrum and relevance of ALDH activity in the putative LSC populations demonstrates, in addition to phenotypic and genetic, also functional heterogeneity of leukemic cells and suggests divergent roles for ALDH activity in normal HSC versus LSC. By acknowledging these differences our study provides a new and useful tool for prospective identification of AML cases in which separation of HSC from LSC is possible. What's new? To understand the precise disease‐driving mechanisms in acute myeloid leukemia (AML), comparison of patient‐matched hematopoietic stem cells (HSC) and leukemia stem cells (LSC) is essential. This study demonstrates the relevance of aldehyde dehydrogenase (ALDH) for the prospective identification of AML cases in which separation of functionally normal HSC from LSC is possible. Increased activity of this biomarker also characterizes a subgroup of patients with adverse outcome, which might be helpful in risk stratification prior to therapy. Overall, this study demonstrates functional heterogeneity of leukemia cells and suggests divergent roles for ALDH activity in normal HSC versus leukemia‐initiating cells.
    Subject(s): acute myeloid leukemia ; aldehyde dehydrogenase ; Aldehyde Dehydrogenase - genetics ; Aldehyde Dehydrogenase - metabolism ; Aldehydes ; Analysis ; Animals ; Bone Marrow - metabolism ; Bone Marrow - pathology ; Cancer ; Cancer Cell Biology ; Case-Control Studies ; Cell Cycle - drug effects ; Cell Cycle - genetics ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - metabolism ; Chemotherapy ; Colony-Forming Units Assay ; Disease Models, Animal ; Drug Resistance, Neoplasm - genetics ; Enzyme Activation ; fms-Like Tyrosine Kinase 3 - genetics ; Gene Expression ; hematopoietic stem cell ; Hematopoietic stem cells ; Hematopoietic Stem Cells - drug effects ; Hematopoietic Stem Cells - metabolism ; Heterografts ; high risk factor ; Humans ; Immunophenotyping ; Leukemia ; leukemia stem cell ; Leukemia, Myeloid, Acute - drug therapy ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - metabolism ; Leukemia, Myeloid, Acute - mortality ; Leukemia, Myeloid, Acute - pathology ; Mice ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Phenotype ; Prognosis
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
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  • 9
    Language: English
    In: Leukemia, 2021-02-17, Vol.35 (9), p.2602-2615
    Description: Elimination of suppressive T cells may enable and enhance cancer immunotherapy. Here, we demonstrate that the cell membrane protein SLAMF7 was highly expressed on immunosuppressive CD8 CD28 CD57 Tregs in multiple myeloma (MM). SLAMF7 expression associated with T cell exhaustion surface markers and exhaustion-related transcription factor signatures. T cells from patients with a high frequency of SLAMF7 CD8 T cells exhibited decreased immunoreactivity towards the MART-1 antigen. A monoclonal anti-SLAMF7 antibody (elotuzumab) specifically depleted SLAMF7 CD8 T cells in vitro and in vivo via macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). Anti-SLAMF7 treatment of MM patients depleted suppressive T cells in peripheral blood. These data highlight SLAMF7 as a marker for suppressive CD8 Treg and suggest that anti-SLAMF7 antibodies can be used to boost anti-tumoral immune responses in cancer patients.
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
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  • 10
    Language: English
    In: Immunology, 2018-10, Vol.155 (2), p.211-224
    Description: Summary Premature aging of both CD4+ regulatory T (Treg) and CD4+ responder‐T (Tresp) cells in patients with end‐stage renal disease (ESRD) is expected to affect the success of later kidney transplantation. Both T‐cell populations are released from the thymus as inducible T‐cell co‐stimulator‐positive (ICOS+) and ICOS− recent thymic emigrant (RTE) Treg/Tresp cells, which differ primarily in their proliferative capacities. In this study, we analysed the effect of ESRD and subsequent renal replacement therapies on the differentiation of ICOS+ and ICOS− RTE Treg/Tresp cells into ICOS+ CD31− or ICOS− CD31− memory Treg/Tresp cells and examined whether diverging pathways affected the suppressive activity of ICOS+ and ICOS− Treg cells in co‐culture with autologous Tresp cells. Compared with healthy controls, we found an increased differentiation of ICOS+ RTE Treg/Tresp cells and ICOS− RTE Treg cells through CD31+ memory Treg/Tresp cells into CD31− memory Treg/Tresp cells in ESRD and dialysis patients. In contrast, ICOS− RTE Tresp cells showed an increased differentiation via ICOS− mature naive (MN) Tresp cells into CD31− memory Tresp cells. Thereby, the ratio of ICOS+ Treg/ICOS+ Tresp cells was not changed, whereas that of ICOS− Treg/ICOS− Tresp cells was significantly increased. This differentiation preserved the suppressive activity of both Treg populations in ESRD and partly in dialysis patients. After transplantation, the increased differentiation of ICOS+ and ICOS− RTE Tresp cells proceeded, whereas that of ICOS+ RTE Treg cells ceased and that of ICOS− RTE Treg cells switched to an increased differentiation via ICOS− MN Treg cells. Consequently, the ratios of ICOS+ Treg/ICOS+ Tresp cells and of ICOS− Treg/ICOS− Tresp cells decreased significantly, reducing the suppressive activity of Treg cells markedly. Our data reveal that an increased tolerance‐inducing differentiation of ICOS+ and ICOS− Treg cells preserves the functional activity of Treg cells in ESRD patients, but this cannot be maintained during long‐term renal replacement therapy. Premature aging of both regulatory (Treg) and responder (Tresp) T cells in end‐stage renal disease (ESRD) patients is expected to affect the success of later kidney transplantation. Changing differentiation pathways of inducible co‐stimulatory ICOS+ and ICOS− RTE Treg/Tresp cells in ESRD (a), dialysis (b), short‐term (c) and long‐term (d) transplant patients are responsible for changes in the ratios of total ICOS+ Treg/ICOS+ Tresp cells and of ICOS−Treg/ICOS− Tresp cells within total CD4+ T helper cells. These ratios were found to influence the suppressive activity of autologous ICOS+ and ICOS− Treg cells in these patients.
    Subject(s): Cell differentiation ; Chronic kidney failure ; end‐stage renal disease ; immunosenescence ; Original ; regulatory T cells ; renal replacement therapy ; T cells ; Transplantation of organs, tissues, etc ; T‐cell differentiation
    ISSN: 0019-2805
    E-ISSN: 1365-2567
    Source: Hellenic Academic Libraries Link
    Source: Academic Search Ultimate
    Source: PubMed Central
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