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  1. Article ; Online: Correlates of physical activity enjoyment in children and adolescents for a new perspective on the treatment of overweight: A systematic literature review.

    Greule, Constanze / Sudeck, Gorden / Thiel, Ansgar / Kastner, Lydia / Janßen, Pia / Nieß, Andreas / Rapp, Felicitas / Junne, Florian / Krauß, Inga

    Obesity reviews : an official journal of the International Association for the Study of Obesity

    2023  Volume 25, Issue 2, Page(s) e13655

    Abstract: The purpose of this systematic literature review was to systematically compile the state of knowledge on correlates of physical activity enjoyment in children and adolescents to influence the perspective of future physical activity promotion approaches ... ...

    Abstract The purpose of this systematic literature review was to systematically compile the state of knowledge on correlates of physical activity enjoyment in children and adolescents to influence the perspective of future physical activity promotion approaches especially for children and adolescents affected by overweight or obesity. The electronic database search was executed in the five databases PubMed, PsychINFO, SPORTDiscus, Web of Science, and BISp-SURF, from inception to December 6, 2021. A semi-quantitative method was used for summarizing the resulted correlates. For final analysis, 85 studies comprising 48,144 children and adolescents were included. Fifty-seven variables could be coded for their relationship with physical activity enjoyment. Of these, 12 psychological variables, for example, the basic psychological needs, task orientation, or self-efficacy; six interpersonal variables, for example, peer/group acceptance, parental support, and autonomy support; and one behavioral variable, the higher self-reported physical activity, are consistent positively associated to physical activity enjoyment. A scientifically based overview could be extracted for the promotion of physical activity enjoyment in children and adolescents. There is a gap in literature focusing the perception of physical activity enjoyment in the subgroup of children and adolescents affected by overweight or obesity. Therefore, recommendations were made to enable the development of further innovative research approaches in this population.
    MeSH term(s) Child ; Adolescent ; Humans ; Overweight/therapy ; Overweight/psychology ; Pleasure ; Exercise/psychology ; Obesity/psychology ; Self Report
    Language English
    Publishing date 2023-11-21
    Publishing country England
    Document type Systematic Review ; Journal Article ; Review
    ZDB-ID 2147980-X
    ISSN 1467-789X ; 1467-7881
    ISSN (online) 1467-789X
    ISSN 1467-7881
    DOI 10.1111/obr.13655
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Osteo-immunological impact of radon spa treatment: due to radon or spa alone? Results from the prospective, thermal bath placebo-controlled RAD-ON02 trial.

    Eckert, Denise / Evic, Megi / Schang, Jasmin / Isbruch, Maike / Er, Melissa / Dörrschuck, Lea / Rapp, Felicitas / Donaubauer, Anna-Jasmina / Gaipl, Udo S / Frey, Benjamin / Fournier, Claudia

    Frontiers in immunology

    2024  Volume 14, Page(s) 1284609

    Abstract: Musculoskeletal disorders (MSDs) are associated with pain and lead to reduced mobility and quality of life for patients. Radon therapy is used as alternative or complementary to pharmaceutical treatments. According to previous reports, radon spa leads to ...

    Abstract Musculoskeletal disorders (MSDs) are associated with pain and lead to reduced mobility and quality of life for patients. Radon therapy is used as alternative or complementary to pharmaceutical treatments. According to previous reports, radon spa leads to analgesic and anti-inflammatory effects, but the cellular and molecular mechanisms are widely unknown. A previous study (RAD-ON01) revealed, that bone erosion markers like collagen fragments (C-terminal telopeptide, CTX) are reduced after radon spa treatment in serum of patients with degenerative MSDs. Within the scope of the prospective, placebo-controlled RAD-ON02 trial presented here, we analyzed the influence of radon and thermal spa treatment on osteoclastogenesis. From patient blood, we isolate monocytes, seeded them on bone slices and differentiated them in the presence of growth factors into mature osteoclasts (mOCs). Subsequent analysis showed a smaller fraction of mOCs after both treatments, which was even smaller after radon spa treatment. A significantly reduced resorbed area on bone slices reflects this result. Only after radon spa treatment, we detected in the serum of patients a significant decrease of receptor activator of NF-κB ligand (RANKL), which indicates reduced differentiation of OCs. However, other markers for bone resorption (CTX) and bone formation (OPG, OCN) were not altered after both treatments. Adipokines, such as visfatin and leptin that play a role in some MSD-types by affecting osteoclastogenesis, were not changed after both treatments. Further, also immune cells have an influence on osteoclastogenesis, by inhibiting and promoting terminal differentiation and activation of OCs, respectively. After radon treatment, the fraction of Treg cells was significantly increased, whereas Th17 cells were not altered. Overall, we observed that both treatments had an influence on osteoclastogenesis and bone resorption. Moreover, radon spa treatment affected the Treg cell population as well as the Th17/Treg ratio were affected, pointing toward a contribution of the immune system after radon spa. These data obtained from patients enrolled in the RAD-ON02 trial indicate that radon is not alone responsible for the effects on bone metabolism, even though they are more pronounced after radon compared to thermal spa treatment.
    MeSH term(s) Humans ; Radon/therapeutic use ; Radon/metabolism ; Prospective Studies ; Quality of Life ; Bone Resorption/metabolism ; Monocytes/metabolism
    Chemical Substances Radon (Q74S4N8N1G)
    Language English
    Publishing date 2024-01-16
    Publishing country Switzerland
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1284609
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: In Silico Pan-Cancer Analysis Reveals Prognostic Role of the Erythroferrone (ERFE) Gene in Human Malignancies.

    Xu, Qingyu / Altrock, Eva / Schmitt, Nanni / Streuer, Alexander / Rapp, Felicitas / Nowak, Verena / Obländer, Julia / Weimer, Nadine / Palme, Iris / Göl, Melda / Hofmann, Wolf-Karsten / Nowak, Daniel / Riabov, Vladimir

    International journal of molecular sciences

    2023  Volume 24, Issue 2

    Abstract: The erythroferrone gene ( ...

    Abstract The erythroferrone gene (
    MeSH term(s) Humans ; Prognosis ; Peptide Hormones/genetics ; Hepcidins/metabolism ; Neoplasms/genetics ; Myelodysplastic Syndromes ; Tumor Microenvironment
    Chemical Substances Peptide Hormones ; Hepcidins
    Language English
    Publishing date 2023-01-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24021725
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: ROS- and Radiation Source-Dependent Modulation of Leukocyte Adhesion to Primary Microvascular Endothelial Cells.

    Eckert, Denise / Rapp, Felicitas / Tsedeke, Ayele T / Molendowska, Jessica / Lehn, Robert / Langhans, Markus / Fournier, Claudia / Rödel, Franz / Hehlgans, Stephanie

    Cells

    2021  Volume 11, Issue 1

    Abstract: Anti-inflammatory effects of low-dose irradiation often follow a non-linear dose-effect relationship. These characteristics were also described for the modulation of leukocyte adhesion to endothelial cells. Previous results further revealed a ... ...

    Abstract Anti-inflammatory effects of low-dose irradiation often follow a non-linear dose-effect relationship. These characteristics were also described for the modulation of leukocyte adhesion to endothelial cells. Previous results further revealed a contribution of reactive oxygen species (ROS) and anti-oxidative factors to a reduced leukocyte adhesion. Here, we evaluated the expression of anti-oxidative enzymes and the transcription factor Nrf2 (Nuclear factor-erythroid-2-related factor 2), intracellular ROS content, and leukocyte adhesion in primary human microvascular endothelial cells (HMVEC) upon low-dose irradiation under physiological laminar shear stress or static conditions after irradiation with X-ray or Carbon (C)-ions (0-2 Gy). Laminar conditions contributed to increased mRNA expression of anti-oxidative factors and reduced ROS in HMVEC following a 0.1 Gy X-ray and 0.5 Gy C-ion exposure, corresponding to reduced leukocyte adhesion and expression of adhesion molecules. By contrast, mRNA expression of anti-oxidative markers and adhesion molecules, ROS, and leukocyte adhesion were not altered by irradiation under static conditions. In conclusion, irradiation of endothelial cells with low doses under physiological laminar conditions modulates the mRNA expression of key factors of the anti-oxidative system, the intracellular ROS contents of which contribute at least in part to leucocyte adhesion, dependent on the radiation source.
    MeSH term(s) Carbon ; Cell Adhesion/radiation effects ; Cell Adhesion Molecules/metabolism ; Cells, Cultured ; Dose-Response Relationship, Radiation ; Endothelial Cells/cytology ; Endothelial Cells/radiation effects ; Gene Expression Regulation/radiation effects ; Humans ; Leukocytes/cytology ; Leukocytes/radiation effects ; Microvessels/cytology ; Models, Biological ; NF-E2-Related Factor 2/metabolism ; Oxidation-Reduction ; Oxidative Stress/radiation effects ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Reactive Oxygen Species/metabolism ; X-Rays
    Chemical Substances Cell Adhesion Molecules ; NF-E2-Related Factor 2 ; NFE2L2 protein, human ; RNA, Messenger ; Reactive Oxygen Species ; Carbon (7440-44-0)
    Language English
    Publishing date 2021-12-27
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11010072
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Treatment with the apoptosis inhibitor Asunercept reduces clone sizes in patients with lower risk Myelodysplastic Neoplasms.

    Streuer, Alexander / Jann, Johann-Christoph / Boch, Tobias / Mossner, Maximilian / Riabov, Vladimir / Schmitt, Nanni / Altrock, Eva / Xu, Qingyu / Demmerle, Marie / Nowak, Verena / Oblaender, Julia / Palme, Iris / Weimer, Nadine / Rapp, Felicitas / Metzgeroth, Georgia / Hecht, Anna / Höger, Thomas / Merz, Christian / Hofmann, Wolf-Karsten /
    Nolte, Florian / Nowak, Daniel

    Annals of hematology

    2024  Volume 103, Issue 4, Page(s) 1221–1233

    Abstract: In low-risk Myelodysplastic Neoplasms (MDS), increased activity of apoptosis-promoting factors such as tumor necrosis factor (TNFα) and pro-apoptotic Fas ligand (CD95L) have been described as possible pathomechanisms leading to impaired erythropoiesis. ... ...

    Abstract In low-risk Myelodysplastic Neoplasms (MDS), increased activity of apoptosis-promoting factors such as tumor necrosis factor (TNFα) and pro-apoptotic Fas ligand (CD95L) have been described as possible pathomechanisms leading to impaired erythropoiesis. Asunercept (APG101) is a novel therapeutic fusion protein blocking CD95, which has previously shown partial efficacy in reducing transfusion requirement in a clinical phase I trial for low-risk MDS patients (NCT01736436; 2012-11-26). In the current study we aimed to evaluate the effect of Asunercept therapy on the clonal bone marrow composition to identify potential biomarkers to predict response. Bone marrow samples of n = 12 low-risk MDS patients from the above referenced clinical trial were analyzed by serial deep whole exome sequencing in a total of n = 58 time points. We could distinguish a mean of 3.5 molecularly defined subclones per patient (range 2-6). We observed a molecular response defined as reductions of dominant clone sizes by a variant allele frequency (VAF) decrease of at least 10% (mean 20%, range: 10.5-39.2%) in dependency of Asunercept treatment in 9 of 12 (75%) patients. Most of this decline in clonal populations was observed after completion of 12 weeks treatment. Particularly early and pronounced reductions of clone sizes were found in subclones driven by mutations in genes involved in regulation of methylation (n = 1 DNMT3A, n = 1 IDH2, n = 1 TET2). Our results suggest that APG101 could be efficacious in reducing clone sizes of mutated hematopoietic cells in the bone marrow of Myelodysplastic Neoplasms, which warrants further investigation.
    MeSH term(s) Humans ; Neoplasms ; Myelodysplastic Syndromes/drug therapy ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/pathology ; Clone Cells/pathology ; Bone Marrow/pathology ; Apoptosis ; Mutation
    Language English
    Publishing date 2024-02-27
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1064950-5
    ISSN 1432-0584 ; 0939-5555 ; 0945-8077
    ISSN (online) 1432-0584
    ISSN 0939-5555 ; 0945-8077
    DOI 10.1007/s00277-024-05664-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Modulation of Differentiation and Bone Resorbing Activity of Human (Pre-) Osteoclasts After X-Ray Exposure.

    Eckert, Denise / Rapp, Felicitas / Tsedeke, Ayele Taddese / Kraft, Daniela / Wente, Isabell / Molendowska, Jessica / Basheer, Sidra / Langhans, Markus / Meckel, Tobias / Friedrich, Thomas / Donaubauer, Anna-Jasmina / Becker, Ina / Frey, Benjamin / Fournier, Claudia

    Frontiers in immunology

    2022  Volume 13, Page(s) 817281

    Abstract: Low-dose radiotherapy (LD-RT) is a local treatment option for patients with chronic degenerative and inflammatory diseases, in particular musculoskeletal diseases. Despite reported analgesic and anti-inflammatory effects, cellular and molecular ... ...

    Abstract Low-dose radiotherapy (LD-RT) is a local treatment option for patients with chronic degenerative and inflammatory diseases, in particular musculoskeletal diseases. Despite reported analgesic and anti-inflammatory effects, cellular and molecular mechanisms related to osteoimmunological effects are still elusive. Here we test the hypothesis that X-irradiation inhibits the differentiation of precursor osteoclasts into mature osteoclasts (mOC) and their bone resorbing activity. Circulating monocytes from healthy donors were isolated and irradiated after attachment with single or fractionated X-ray doses, comparable to an LD-RT treatment scheme. Then monocytes underwent
    MeSH term(s) Bone Resorption/metabolism ; Cytokines/metabolism ; Humans ; Osteoclasts/metabolism ; X-Rays
    Chemical Substances Cytokines ; bone resorption factor
    Language English
    Publishing date 2022-05-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.817281
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: RNA sequencing of glioblastoma tissue slice cultures reveals the effects of treatment at the transcriptional level

    Haehnel, Susann / Rade, Michael / Kaiser, Nicole / Reiche, Kristin / Horn, Andreas / Loeffler, Dennis / Blumert, Conny / Rapp, Felicitas / Horn, Friedemann / Meixensberger, Juergen / Renner, Christof / Mueller, Wolf / Gaunitz, Frank / Bechmann, Ingo / Winter, Karsten

    FEBS Open Bio. 2022 Feb., v. 12, no. 2

    2022  

    Abstract: One of the major challenges in cancer research is finding models that closely resemble tumors within patients. Human tissue slice cultures are a promising approach to provide a model of the patient's tumor biology ex vivo. Recently, it was shown that ... ...

    Abstract One of the major challenges in cancer research is finding models that closely resemble tumors within patients. Human tissue slice cultures are a promising approach to provide a model of the patient's tumor biology ex vivo. Recently, it was shown that these slices can be successfully analyzed by whole transcriptome sequencing as well as automated histochemistry, increasing their usability as preclinical model. Glioblastoma multiforme (GBM) is a highly malignant brain tumor with poor prognosis and little is known about its genetic background and heterogeneity regarding therapy success. In this study, tissue from the tumors of 25 patients with primary GBM was processed into slice cultures and treated with standard therapy (irradiation and temozolomide). Total RNA sequencing and automated histochemistry were performed to enable analysis of treatment effects at a transcriptional and histological level. Slice cultures from long‐term survivors (overall survival [OS] > 24 months) exhibited more apoptosis than cultures from patients with shorter OS. Proliferation within these slices was slightly increased in contrast to other groups, but not significantly. Among all samples, 58 protein‐coding genes were upregulated and 32 downregulated in treated vs. untreated slice cultures. In general, an upregulation of DNA damage‐related and cell cycle checkpoint genes as well as enrichment of genotoxicity pathways and p53‐dependent signaling was found after treatment. Overall, the current study reproduces knowledge from former studies regarding the feasibility of transcriptomic analyses and automated histology in tissue slice cultures. We further demonstrate that the experimental data merge with the clinical follow‐up of the patients, which improves the applicability of our model system.
    Keywords DNA ; RNA ; apoptosis ; automation ; brain neoplasms ; cell cycle checkpoints ; genetic background ; genotoxicity ; glioblastoma ; histochemistry ; humans ; irradiation ; models ; patients ; prognosis ; therapeutics ; transcription (genetics) ; transcriptome ; transcriptomics
    Language English
    Dates of publication 2022-02
    Size p. 480-493.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 2651702-4
    ISSN 2211-5463
    ISSN 2211-5463
    DOI 10.1002/2211-5463.13353
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Examination of ex-vivo viability of human adipose tissue slice culture.

    Schopow, Nikolas / Kallendrusch, Sonja / Gong, Siming / Rapp, Felicitas / Körfer, Justus / Gericke, Martin / Spindler, Nick / Josten, Christoph / Langer, Stefan / Bechmann, Ingo

    PloS one

    2020  Volume 15, Issue 5, Page(s) e0233152

    Abstract: Obesity is associated with significantly higher mortality rates, and excess adipose tissue is involved in respective pathologies. Here we established a human adipose tissue slice cultures (HATSC) model ex vivo. HATSC match the in vivo cell composition of ...

    Abstract Obesity is associated with significantly higher mortality rates, and excess adipose tissue is involved in respective pathologies. Here we established a human adipose tissue slice cultures (HATSC) model ex vivo. HATSC match the in vivo cell composition of human adipose tissue with, among others, mature adipocytes, mesenchymal stem cells as well as stroma tissue and immune cells. This is a new method, optimized for live imaging, to study adipose tissue and cell-based mechanisms of obesity in particular. HATSC survival was tested by means of conventional and immunofluorescence histological techniques, functional analyses and live imaging. Surgery-derived tissue was cut with a tissue chopper in 500 μm sections and transferred onto membranes building an air-liquid interface. HATSC were cultured in six-well plates filled with Dulbecco's Modified Eagle's Medium (DMEM), insulin, transferrin, and selenium, both with and without serum. After 0, 1, 7 and 14 days in vitro, slices were fixated and analyzed by morphology and Perilipin A for tissue viability. Immunofluorescent staining against IBA1, CD68 and Ki67 was performed to determine macrophage survival and proliferation. These experiments showed preservation of adipose tissue as well as survival and proliferation of monocytes and stroma tissue for at least 14 days in vitro even in the absence of serum. The physiological capabilities of adipocytes were functionally tested by insulin stimulation and measurement of Phospho-Akt on day 7 and 14 in vitro. Viability was further confirmed by live imaging using Calcein-AM (viable cells) and propidium iodide (apoptosis/necrosis). In conclusion, HATSC have been successfully established by preserving the monovacuolar form of adipocytes and surrounding macrophages and connective tissue. This model allows further analysis of mature human adipose tissue biology ex vivo.
    MeSH term(s) Adipocytes/metabolism ; Adipocytes/pathology ; Adipose Tissue/metabolism ; Adipose Tissue/pathology ; Adolescent ; Adult ; Aged ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Calcium-Binding Proteins/metabolism ; Cell Survival ; Female ; Humans ; Ki-67 Antigen/metabolism ; Male ; Microfilament Proteins/metabolism ; Middle Aged ; Models, Biological ; Obesity/metabolism ; Obesity/pathology ; Tissue Culture Techniques
    Chemical Substances AIF1 protein, human ; Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; CD68 antigen, human ; Calcium-Binding Proteins ; Ki-67 Antigen ; MKI67 protein, human ; Microfilament Proteins
    Language English
    Publishing date 2020-05-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0233152
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: RNA sequencing of glioblastoma tissue slice cultures reveals the effects of treatment at the transcriptional level.

    Haehnel, Susann / Rade, Michael / Kaiser, Nicole / Reiche, Kristin / Horn, Andreas / Loeffler, Dennis / Blumert, Conny / Rapp, Felicitas / Horn, Friedemann / Meixensberger, Juergen / Renner, Christof / Mueller, Wolf / Gaunitz, Frank / Bechmann, Ingo / Winter, Karsten

    FEBS open bio

    2021  Volume 12, Issue 2, Page(s) 480–493

    Abstract: One of the major challenges in cancer research is finding models that closely resemble tumors within patients. Human tissue slice cultures are a promising approach to provide a model of the patient's tumor biology ex vivo. Recently, it was shown that ... ...

    Abstract One of the major challenges in cancer research is finding models that closely resemble tumors within patients. Human tissue slice cultures are a promising approach to provide a model of the patient's tumor biology ex vivo. Recently, it was shown that these slices can be successfully analyzed by whole transcriptome sequencing as well as automated histochemistry, increasing their usability as preclinical model. Glioblastoma multiforme (GBM) is a highly malignant brain tumor with poor prognosis and little is known about its genetic background and heterogeneity regarding therapy success. In this study, tissue from the tumors of 25 patients with primary GBM was processed into slice cultures and treated with standard therapy (irradiation and temozolomide). Total RNA sequencing and automated histochemistry were performed to enable analysis of treatment effects at a transcriptional and histological level. Slice cultures from long-term survivors (overall survival [OS] > 24 months) exhibited more apoptosis than cultures from patients with shorter OS. Proliferation within these slices was slightly increased in contrast to other groups, but not significantly. Among all samples, 58 protein-coding genes were upregulated and 32 downregulated in treated vs. untreated slice cultures. In general, an upregulation of DNA damage-related and cell cycle checkpoint genes as well as enrichment of genotoxicity pathways and p53-dependent signaling was found after treatment. Overall, the current study reproduces knowledge from former studies regarding the feasibility of transcriptomic analyses and automated histology in tissue slice cultures. We further demonstrate that the experimental data merge with the clinical follow-up of the patients, which improves the applicability of our model system.
    MeSH term(s) Brain Neoplasms/genetics ; Glioblastoma/metabolism ; Humans ; Sequence Analysis, RNA ; Temozolomide/pharmacology ; Temozolomide/therapeutic use ; Whole Exome Sequencing
    Chemical Substances Temozolomide (YF1K15M17Y)
    Language English
    Publishing date 2021-12-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2651702-4
    ISSN 2211-5463 ; 2211-5463
    ISSN (online) 2211-5463
    ISSN 2211-5463
    DOI 10.1002/2211-5463.13353
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Significant improvement of bone marrow-derived MSC expansion from MDS patients by defined xeno-free medium.

    Altrock, Eva / Sens-Albert, Carla / Hofmann, Franziska / Riabov, Vladimir / Schmitt, Nanni / Xu, Qingyu / Jann, Johann-Christoph / Rapp, Felicitas / Steiner, Laurenz / Streuer, Alexander / Nowak, Verena / Obländer, Julia / Weimer, Nadine / Palme, Iris / Göl, Melda / Darwich, Ali / Wuchter, Patrick / Metzgeroth, Georgia / Jawhar, Mohamad /
    Hofmann, Wolf-Karsten / Nowak, Daniel

    Stem cell research & therapy

    2023  Volume 14, Issue 1, Page(s) 156

    Abstract: Background: Robust and reliable in vitro and in vivo models of primary cells are necessary to study the pathomechanisms of Myelodysplastic Neoplasms (MDS) and identify novel therapeutic strategies. MDS-derived hematopoietic stem and progenitor cells ( ... ...

    Abstract Background: Robust and reliable in vitro and in vivo models of primary cells are necessary to study the pathomechanisms of Myelodysplastic Neoplasms (MDS) and identify novel therapeutic strategies. MDS-derived hematopoietic stem and progenitor cells (HSPCs) are reliant on the support of bone marrow (BM) derived mesenchymal stroma cells (MSCs). Therefore, isolation and expansion of MCSs are essential for successfully modeling this disease. For the clinical use of healthy MSCs isolated from human BM, umbilical cord blood or adipose tissue, several studies showed that xeno-free (XF) culture conditions resulted in superior growth kinetics compared to MSCs cultured in the presence of fetal bovine serum (FBS). In this present study, we investigate, whether the replacement of a commercially available MSC expansion medium containing FBS with a XF medium is beneficial for the expansion of MSCs derived from BM of MDS patients which are often difficult to cultivate.
    Methods: MSCs isolated from BM of MDS patients were cultured and expanded in MSC expansion medium with FBS or XF supplement. Subsequently, the impact of culture media on growth kinetics, morphology, immunophenotype, clonogenic potential, differentiation capacity, gene expression profiles and ability to engraft in immunodeficient mouse models was evaluated.
    Results: Significant higher cell numbers with an increase in clonogenic potential were observed during culture of MDS MSCs with XF medium compared to medium containing FBS. Differential gene expression showed an increase in transcripts associated with MSC stemness after expansion with XF. Furthermore, immunophenotypes of the MSCs and their ability to differentiate into osteoblasts, adipocytes or chondroblasts remained stable. MSCs expanded with XF media were similarly supportive for creating MDS xenografts in vivo as MSCs expanded with FBS.
    Conclusion: Our data indicate that with XF media, higher cell numbers of MDS MSCs can be obtained with overall improved characteristics in in vitro and in vivo experimental models.
    MeSH term(s) Animals ; Mice ; Humans ; Culture Media, Serum-Free ; Bone Marrow ; Cell Differentiation ; Mesenchymal Stem Cells/metabolism ; Adipose Tissue ; Cell Proliferation ; Cells, Cultured
    Chemical Substances Culture Media, Serum-Free
    Language English
    Publishing date 2023-06-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2548671-8
    ISSN 1757-6512 ; 1757-6512
    ISSN (online) 1757-6512
    ISSN 1757-6512
    DOI 10.1186/s13287-023-03386-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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