33 results on '"Saulnier, N."'
Search Results
2. Yield Methodology and Heater Process Variation in Phase Change Memory (PCM) Technology for Analog Computing.
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Chan, Victor, Gasasira, A., Pujari, R., Tseng, W.-T., Gordon, T., Southwick, R., Ok, I., Choi, S., Silvestre, C., Utomo, H., Brew, K., Philip, T., Burr, G. W., Saulnier, N., Teehan, S., and Ahsan, I.
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PHASE change memory ,DIRECT-fired heaters ,PHASE transitions ,RESISTANCE heating ,PHASE change materials - Abstract
We discuss inline electrical testing to monitor the baseline of Analog Computing hardware using Phase Change Memory (PCM) technology. Tightening the PCM resistance distribution is necessary to meet analog computation requirement. A new yield methodology is introduced. A study of heater process variation, which will affect the heater height and the PCM resistance, will be discussed. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Intra-articular administration of xenogeneic neonatal Mesenchymal Stromal Cells early after meniscal injury down-regulates metalloproteinase gene expression in synovium and prevents cartilage degradation in a rabbit model of osteoarthritis
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Saulnier, N., Viguier, E., Perrier-Groult, E., Chenu, C., Pillet, E., Roger, T., Maddens, S., and Boulocher, C.
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- 2015
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4. Fully On-Chip MAC at 14 nm Enabled by Accurate Row-Wise Programming of PCM-Based Weights and Parallel Vector-Transport in Duration-Format
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Narayanan, P., primary, Ambrogio, S., additional, Okazaki, A., additional, Hosokawa, K., additional, Tsai, H., additional, Nomura, A., additional, Yasuda, T., additional, Mackin, C., additional, Lewis, S. C., additional, Friz, A., additional, Ishii, M., additional, Kohda, Y., additional, Mori, H., additional, Spoon, K., additional, Khaddam-Aljameh, R., additional, Saulnier, N., additional, Bergendahl, M., additional, Demarest, J., additional, Brew, K. W., additional, Chan, V., additional, Choi, S., additional, Ok, I., additional, Ahsan, I., additional, Lie, F. L., additional, Haensch, W., additional, Narayanan, V., additional, and Burr, G. W., additional
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- 2021
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5. A novel cell-based strategy based on MHCI/CD90 expression levels for highly proliferative MSC identification
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Rakic, R., primary, Maddens, S., additional, Robert, C., additional, Rosset, E., additional, and Saulnier, N., additional
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- 2020
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6. Single infusion of allogeneic neonatal Mesenchymal stromal cells to manage refractory feline gingivostomatitis- A clinical pilot study
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Febre, M., primary, Maddens, S., additional, Robert, C., additional, Rakic, R., additional, Plantier, N., additional, and Saulnier, N., additional
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- 2020
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7. Analytical TEM Characterization of Source/Drain Contacts in Advanced Semiconductor Devices
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Li, J., primary, Niimi, H., additional, Gluschenkov, O., additional, Adusumilli, P., additional, Fronheiser, J., additional, Mochizuki, S., additional, Liu, Z., additional, Kamineni, V., additional, Raymond, M., additional, Carr, A. V, additional, Yamashita, T., additional, Veeraraghavan, B., additional, Saulnier, N., additional, and Gaudiello, J., additional
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- 2018
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8. Early intra-articular injection of mesenchymal stem cells prevents synovial inflammation after medial meniscal release in a rabbit model of osteoarthritis
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Boulocher, C., primary, Saulnier, N., additional, Maddens, S., additional, Pillet, E., additional, Roger, T., additional, and Viguier, E., additional
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- 2014
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9. Early UC-MSC injection dampens the synovial catabolic activity in early-stage of experimental osteoarthritis
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Saulnier, N., primary, Boulocher, C., additional, Maddens, S., additional, Pillet, E., additional, Roger, T., additional, and Viguier, E., additional
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- 2014
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10. S2066 In Vitro Evaluation of Hepatic Transdifferentiation of Adipose and Bone Marrow-Derived Stromal Cells
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SAULNIER, N, primary, PUGLISI, M, additional, BARBA, M, additional, PISCAGLIA, A, additional, NOVI, M, additional, LAURITANO, E, additional, ALFIERI, S, additional, LEONE, G, additional, GASBARRINI, G, additional, and GASBARRINI, A, additional
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- 2008
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11. M1998 Identification of Human Gastric-Cancer Stem Cells
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Puglisi, M., primary, Saulnier, N., additional, Sgambato, A., additional, Barba, M., additional, Lauritano, Ernesto Cristiano, additional, Boninsegna, A., additional, Piscaglia, A., additional, Novi, Marialuisa, additional, Zocco, Maria Assunta, additional, Barbaro, F., additional, Fiore, Francesca, additional, Alfieri, S., additional, Doglietto, G., additional, Cittadini, A., additional, Michetti, F., additional, and Gasbarrini, Antonio, additional
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- 2008
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12. M1999 Identification of CD133-Cancer Stem Cells in Hepatic Metastasis from Colon Cancer
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Puglisi, M., primary, Saulnier, N., additional, Sgambato, A., additional, Barba, M., additional, Novi, Marialuisa, additional, Boninsegna, A., additional, Piscaglia, Anna C., additional, Lauritano, Ernesto Cristiano, additional, Zocco, Maria Assunta, additional, Rinninella, E., additional, Campanale, Mariachiara, additional, Fiore, Francesca, additional, Giuliante, F., additional, Nuzzo, G., additional, Cittadini, A., additional, Michetti, F., additional, and Gasbarrini, Antonio, additional
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- 2008
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13. Probiotics and small bowel mucosa: Molecular aspects of their interactions
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Saulnier, N., primary, Zocco, M. A., additional, Di Caro, S., additional, Gasbarrini, G., additional, and Gasbarrini, A., additional
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- 2006
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14. Analytical TEM Characterization of Source/Drain Contacts in Advanced Semiconductor Devices.
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Li, J., Niimi, H., Gluschenkov, O., Adusumilli, P., Fronheiser, J., Mochizuki, S., Liu, Z., Kamineni, V., Raymond, M., Carr, A. V, Yamashita, T., Veeraraghavan, B., Saulnier, N., and Gaudiello, J.
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- 2019
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15. Mesenchymal stromal cells multipotency and plasticity: Induction toward the hepatic lineage
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Saulnier, N., Lattanzi, W., Puglisi, M. A., Pani, G., Barba, M., Piscaglia, A. C., Giachelia, M., Sergio Alfieri, Neri, G., Gasbarrini, G., and Gasbarrini, A.
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Settore BIO/16 - ANATOMIA UMANA ,mesenchymal stem cells ,Multipotent Stem Cells ,Bone Marrow Cells ,Cell Differentiation ,differentiation ,Amniotic Fluid ,Antigens, Differentiation ,Adipose Tissue ,Organ Specificity ,Pregnancy ,Hepatocytes ,Humans ,Female ,hepatic lineage ,Cells, Cultured ,Cell Proliferation - Abstract
Human mesenchymal stromal cells (MSCs) can be isolated from a variety of adult and perinatal tissues and exert multipotency and self renewal properties which make them suitable for cell-based therapy. Their potential plasticity extended to non-mesodermal-derived tissues has been indicated, although it is still a debated issue. In this study we have isolated MSCs from both adult and fetal tissues. Their growth, immunophenotype and multi-lineage differentiation potentials have been analyzed, focusing, in particular, on the hepatic differentiation.Cells were isolated from bone marrow (BMSC), adipose tissue (ATSC) and second trimester amniotic fluid (AFSC), upon a written informed consent obtained from donor patients. Cells were expanded and growth kinetics was assessed by means of proliferation assay. Their immunophenotype was analyzed using cytometry and multi-lineage differentiation potential was evaluated by means of in vitro differentiation assays. Finally, the expression of tissue-specific markers was also assessed by mean of semi-quantitative PCR.Bipolar spindle-shaped cells were successfully isolated from all these tissues. Interestingly, ATSCs and AFSCs showed a higher proliferation potential than BMSCs. Mesodermal differentiation capacity was verified in all MSC populations, even if AFSCs were not able to undergo adipogenesis in our culture conditions. Furthermore, we showed that MSC cultured in appropriate conditions were able to induce hepatic-associated genes, such as ALB and TDO2.Taken together the data here reported suggest that MSCs from both adult and fetal tissues are capable of tissue-specific commitment along mesodermal and non-mesodermal lineages. In particular we have demonstrated that a specific hepatogenic commitment can be efficiently induced, proposing these cells as suitable tool for cell-based applications aimed at liver regeneration.
16. Gene expression profiling of patients with latex and/or vegetable food allergy
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Saulnier N, Nucera E, Altomonte G, Rizzi A, Pecora V, Aruanno A, Buonomo A, Antonio Gasbarrini, Patriarca G, and Schiavino D
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Adult ,Male ,Gene Expression Profiling ,Settore MED/12 - GASTROENTEROLOGIA ,Real-Time Polymerase Chain Reaction ,T-Lymphocytes, Regulatory ,Latex Hypersensitivity ,Vegetables ,Humans ,Female ,latex allergy ,vegetable food allergy ,Food Hypersensitivity ,Oligonucleotide Array Sequence Analysis - Abstract
The prevalence of individuals allergic to latex, exhibiting cross-hypersensitivity with plant-derived food has been frequently reported as the so-called latex-fruit syndrome. Nonetheless, molecular mechanisms underlying allergy to latex and/or fruit are poorly understood.The aims of this study were to identify candidate genes that may be associated with the pathogenesis of allergy to latex and/or vegetable food, and to assess if similar molecular pathways are involved in both types of hypersensitivity.DNA microarray analysis was performed to screen the molecular profiles of peripheral blood mononuclear cells isolated from patients with allergy to latex, to fruit, or with latex-fruit syndrome, and from control healthy subjects.Molecular profiling identified an overlapping dataset of genes commonly regulated in all the atopic patients enrolled in this study, suggesting that similar molecular mechanisms are involved in the pathogenesis of allergy to the fruit and/or latex. Several regulators of the innate and acquired immunity reported to polarize the immunological response towards a Th2-mediated immune response were overexpressed in the patients. Evidences suggested that the expression of T-regulatory cells might be defective in allergic patients, as a consequence of a dysregulation of some inflammatory cytokines. Finally, several transcription factors that may be responsible for the Th1/Th2 imbalance were modulated in allergic patients.This study identified relevant genes that may help to elucidate the molecular mechanisms underlying allergic disease. Knowledges of critical targets, along with transcription factors regulating gene activity may facilitate the development of new therapeutic options.
17. Early transcriptional events during osteogenic differentiation of human bone marrow stromal cells induced by Lim Mineralization Protein 3
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Claudio Parrilla, Enrico Pola, Paul D. Robbins, Nathalie Saulnier, Wanda Lattanzi, Andrea Gambotto, Camilla Bernardini, Fabrizio Michetti, Bernardini, C, Saulnier, N, Parrilla, C, Pola, E, Gambotto, A, Michetti, F, Robbins, Pd, and Lattanzi, W
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Stromal cell ,Transcription, Genetic ,Bone Matrix ,Bone Marrow Cells ,Biology ,Microarray ,Bone morphogenetic protein ,Article ,Adenoviridae ,osteogenesis ,Calcification, Physiologic ,Transduction, Genetic ,Gene expression ,Genetics ,medicine ,Mesechymal cells ,Humans ,Molecular Biology ,Cell Proliferation ,Oligonucleotide Array Sequence Analysis ,Settore BIO/16 - ANATOMIA UMANA ,Regulation of gene expression ,Models, Genetic ,Reverse Transcriptase Polymerase Chain Reaction ,Microarray analysis techniques ,Gene Expression Profiling ,Mesenchymal stem cell ,Intracellular Signaling Peptides and Proteins ,Reproducibility of Results ,Cell Differentiation ,Mesenchymal Stem Cells ,Osteoblast ,LIM Domain Proteins ,osteogenesi ,Cell biology ,Gene expression profiling ,Mesechymal cell ,medicine.anatomical_structure ,Gene Expression Regulation ,Lim mineralization protein-3 (LMP3) ,Stromal Cells - Abstract
Lim mineralization protein-3 (LMP3) induces osteoblast differentiation by regulating the expression and activity of certain molecules involved in the osteogenic cascade, including those belonging to the bone morphogenetic protein (BMP) family. The complete network of molecular events involved in LMP3-mediated osteogenesis is still unknown. The aim of this study was to analyze the genome-wide gene expression profiles in human mesenchymal stem cells (hMSC) induced by exogenous LMP3 to mediate osteogenesis. For this purpose hMSC were transduced with a defective adenoviral vector expressing the human LMP3 gene and microarray analysis was performed 1 day post-adenoviral transduction. Cells transduced with the vector backbone and untransduced cells were used as independent controls in the experiments. Microarray data were independently validated by means of real-time PCR on selected transcripts. The statistical analysis of microarray data produced a list of 263 significantly (p < 0.01) differentially expressed transcripts. The biological interpretation of the results indicated, among the most noteworthy effects, the modulation of genes involved in the TGF-beta1 pathway: 88 genes coding for key regulators of the cell cycle regulatory machinery and 28 genes implicated in the regulation of cell proliferation along with the development of connective, muscular, and skeletal tissues. These results suggested that LMP3 could affect the fine balance between cell proliferation/differentiation of mesenchymal cells mostly by modulating the TGF-beta1 signaling pathway.
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- 2010
18. Encephalic nocardiosis after mild COVID-19: A case report.
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Bouhamdani N, Comeau D, Bourque C, and Saulnier N
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The COVID-19 pandemic and the associated post-acute sequelae of COVID-19 (PASC) have led to the identification of a complex disease phenotype that is associated with important changes in the immune system. Herein, we describe a unique case of Nocardia farcinica cerebral abscess in an individual with sudden immunodeficiency several months after mild COVID-19. Intravenous Bactrim and Imipenem were prescribed for 6 weeks. After this, a 12-month course of Bactrim and Clavulin was prescribed to be taken orally, given the N. farcinica infection at the level of the central nervous system. This case report highlights the need for future research into the pathophysiology of COVID-19 and PASC immune dysregulation in convalescent individuals. It also draws attention to the need for timely consideration of opportunistic infections in patients with a history of COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bouhamdani, Comeau, Bourque and Saulnier.)
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- 2023
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19. Equine Umbilical Cord Serum Composition and Its Healing Effects in Equine Corneal Ulceration.
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Peyrecave-Capo X, Saulnier N, Maddens S, Gremillet B, and Desjardins I
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Background: Human autologous serum (AS) and umbilical cord serum (UCS) both contain growth and neurotrophic factors that promote corneal healing., Aim: Our objectives were to compare equine AS and UCS cytokine and growth factor profiles and to assess the safety and clinical feasibility of the therapeutic use of UCS eye drops in cases of spontaneous complex ulcers., Study Design: Prospective clinical trial., Methods: Vitamin A insulin growth factor, platelet-derived growth factor-BB, transforming growth factor (TGF)-β1 (enzyme-linked immunosorbent assay), interleukin (IL)-1β, IL-6, interferon-γ, and monocyte chemoattractant protein 1 concentrations were determined in 10 AS collected from different horses and 10 UCS sampled at delivery. Six client-owned horses presenting with complex non-healing corneal defects of >5 mm
2 were included in a clinical trial and treated with conventional therapy and conditioned UCS drops for 8-15 days. Ulcer surface and time to complete epithelialization were recorded., Results: Median concentrations of vitamin A, insulin growth factor, and platelet-derived growth factor-BB were not significantly different in AS compared with UCS (respectively, 14.5 vs . 12.05 μg/ml; 107.8 vs . 107.3 pg/ml; and 369.1 vs . 924.2 pg/ml). TGF-β1 median concentration in UCS was significantly higher than in AS (3,245 vs . 2571pg/ml) ( p = 0.04). IL-1β, IL-6, interferon-γ, and monocyte chemoattractant protein 1 concentrations were variable in AS and undetectable in UCS. The corneal median ulcerative area was 37.2 mm2 (6.28-57.14 mm2 ) and had a duration of 4-186 days (median 19 days). All lesions healed within 13-42 days (median 17 days). No adverse effects nor recurrences within 1 month were noticed., Limitations: The sample size was small. Spontaneous corneal epithelial defects presented with variable clinical characteristics. There were no age-matched control horses to assess corneal healing time and rate., Conclusion and Clinical Significance: Equine UCS may be beneficial, as it contains no pro-inflammatory cytokines and a greater concentration of TGF-β1 compared with AS. Topical UCS appears safe and may potentially be used as adjunctive therapy for equine complex non-healing ulcers., Competing Interests: SM and NS are employees and shareholders of Vetbiobank at the time of the submission for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Peyrecave-Capo, Saulnier, Maddens, Gremillet and Desjardins.)- Published
- 2022
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20. Systematic review shows no strong evidence regarding the use of elastic taping for pain improvement in patients with primary knee osteoarthritis.
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Heddon S, Saulnier N, Mercado J, Shalmiyev M, and Berteau JP
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- Arthralgia diagnosis, Arthralgia etiology, Humans, Osteoarthritis, Knee therapy, Pain Measurement statistics & numerical data, Treatment Outcome, Arthralgia therapy, Compression Bandages, Osteoarthritis, Knee complications, Pain Management methods
- Abstract
Background: A recent trend in the field of primary knee osteoarthritis suggests that elastic tape (e.g., K-tape) relieves pressure on the joint by increasing tension on fascia. Elastic tape (ET) is expected to decrease pain and help patients to recover faster., Objective: This systematic review aims to analyze the efficacy of this method on pain in patients with knee osteoarthritis by using The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score., Data Sources: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard for reporting systematic reviews of qualitative and quantitative evidence, we used 3 electronic databases, PubMed, Cochrane, and EBSCO, and grey literature was included., Study Eligibility Criteria: Articles were screened for duplicates, screened for inclusion and exclusion criteria, and critically appraised., Participants and Intervention: People older than 45 years old with primary osteoarthritis (OA) and application of ET., Study Appraisal and Synthesis Methods: 2005 Oxford standard., Results: Amongst all the papers found, 6 Randomized Control Trials (RCT) for a total of 392 participants met the criteria and were included in our review. Three papers out of the 6 RCT had low risks of bias. When the ET was compared to sham taping, the results show no to moderate decreases of WOMAC scores in patients with primary knee osteoarthritis., Limitations: We focused on a single index test (WOMAC) and could not perform meta-analyses., Conclusion and Implications of Key Findings: Although ET does not provide strong adverse outcomes, our data do not support the use of ET as a treatment alone because of too slight reductions of the WOMAC score for reaching clinical efficiency. Thus, our systematic review shows no strong evidence regarding the use of elastic taping for pain improvement in patients with primary knee osteoarthritis., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2021
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21. Publisher Correction: Differences in the intrinsic chondrogenic potential of equine umbilical cord matrix and cord blood mesenchymal stromal/stem cells for cartilage regeneration.
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Rakic R, Bourdon B, Demoor M, Maddens S, Saulnier N, and Galéra P
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
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22. Biosafety Evaluation of Equine Umbilical Cord-Derived Mesenchymal Stromal Cells by Systematic Pathogen Screening in Peripheral Maternal Blood and Paired UC-MSCs.
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Denys M, Léon A, Robert C, Saulnier N, Josson-Schramme A, Legrand L, Wimel L, Maddens S, and Pronost S
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- Animals, Biological Specimen Banks, Containment of Biohazards, Female, Horses, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear microbiology, Leukocytes, Mononuclear parasitology, Mesenchymal Stem Cells microbiology, Mesenchymal Stem Cells parasitology, Bacteria isolation & purification, Mesenchymal Stem Cells cytology, Piroplasmida isolation & purification, Umbilical Cord cytology, Viruses isolation & purification
- Abstract
Background: The growing interest in mesenchymal stromal cells (MSCs) in equine medicine, together with the development of MSC biobanking for allogeneic use, raises concerns about biosafety of such products. MSCs derived from umbilical cord (UC) carry an inherent risk of contamination by environmental conditions and vertical transmission of pathogens from broodmares. There is yet no report in the scientific literature about horses being contaminated by infected MSC products, and no consensus about systematic infectious screening of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) to ensure microbiological safety of therapeutic products. Objectives: To develop a standard protocol to ensure UC-MSC microbiological safety and to assess the risk of vertical transmission of common intracellular pathogens from broodmares to paired UC-MSCs. Study Design and Methods: Eighty-four UC and paired peripheral maternal blood (PMB) samples were collected between 2014 and 2016. Sterility was monitored by microbiological control tests. Maternal contamination was tested by systematical PMB PCR screening for 14 pathogens and a Coggins test. In case of a PCR-positive result regarding one or several pathogen(s) in PMB, a PCR analysis for the detected pathogen(s) was then conducted on the associated UC-MSCs. Results: Ten out of 84 UC samples were contaminated upon extraction and 6/84 remained positive in primo culture. The remaining 78/84 paired PMB & UC-MSC samples were evaluated for vertical transmission; 37/78 PMB samples were PCR positive for Equid herpesvirus (EHV)-1, EHV-2, EHV-5, Theileria equi , Babesia caballi , and/or Mycoplasma spp . Hepacivirus was detected in 2/27 cases and Theiler Diseases Associated Virus in 0/27 cases (not performed on all samples due to late addition). All paired UC-MSC samples tested for the specific pathogen(s) detected in PMB were negative (37/37). Main Limitations: More data are needed regarding MSC susceptibility to most pathogens detected in PMB. Conclusions: In-process microbiological controls combined with PMB PCR screening provide a comprehensive assessment of UC-MSC exposure to infectious risk, vertical transmission risk appearing inherently low.
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- 2020
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23. Comparison of efficacy and safety of single versus repeated intra-articular injection of allogeneic neonatal mesenchymal stem cells for treatment of osteoarthritis of the metacarpophalangeal/metatarsophalangeal joint in horses: A clinical pilot study.
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Magri C, Schramme M, Febre M, Cauvin E, Labadie F, Saulnier N, François I, Lechartier A, Aebischer D, Moncelet AS, and Maddens S
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- Allografts, Animals, Female, Horse Diseases pathology, Horse Diseases physiopathology, Male, Osteoarthritis pathology, Osteoarthritis physiopathology, Horse Diseases therapy, Horses, Mesenchymal Stem Cell Transplantation, Metacarpophalangeal Joint, Metatarsophalangeal Joint, Osteoarthritis therapy
- Abstract
The purpose of this prospective study was to evaluate the effects of single and repeated intra-articular administration of allogeneic, umbilical cord-derived, neonatal mesenchymal stem cells (MSC) in horses with lameness due to osteoarthritis (OA) of a metacarpophalangeal joint (MPJ). Twenty-eight horses were included. Horses were divided into two groups. Horses in group MSC1 received an MSC injection at M0 and a placebo injection at M1 (1 month after M0). Horses in group MSC2 received MSC injections at M0 and at M1. Joint injections were performed with a blinded syringe. Clinical assessment was performed by the treating veterinarian at M1, M2 and M6 (2 and 6 months after M0), including lameness evaluation, palpation and flexion of the joint. Radiographic examination of the treated joints was performed at inclusion and repeated at M6. Radiographs were anonymized and assessed by 2 ECVDI LA associate members. Short term safety assessment was performed by owner survey. A 2-month rehabilitation program was recommended to veterinarians. There was a significant improvement of the total clinical score for horses in both groups. There was no significant difference in the total clinical score between groups MSC1 and MSC2 at any time point in the study. There was no significant difference in the total radiographic OA score, osteophyte score, joint space width score and subchondral bone score between inclusion and M6. Owner-detected adverse effects to MSC injection were recorded in 18% of the horses. Lameness caused by OA improved significantly over the 6-month duration of the study after treatment with allogeneic neonatal umbilical cord-derived MSCs combined with 8 weeks rest and rehabilitation. There is no apparent clinical benefit of repeated intra-articular administration of MSCs at a 1-month interval in horses with MPJ OA when compared to the effect of a single injection., Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: SM is a current and principal shareholder of Vetbiobank. MF, FL, NS, are employees of Vetbiobank. There is no commercial or financial connection between Vetbiobank and the seven co-authors (CM, MS, EC, IF, AL, DA, AM). EC is shareholder of Azurvet. The product used in this study is developed for commercial use in France and Europe. There are no patents associated with this research to declare. These commercial affiliations do not alter adherence of all authors to all PLOS ONE policies on sharing data and materials. MS and CM are current employees of the National Veterinary School Of Lyon, Vetagro Sup in France.
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- 2019
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24. Long-Term Safety and Efficacy of Single or Repeated Intra-Articular Injection of Allogeneic Neonatal Mesenchymal Stromal Cells for Managing Pain and Lameness in Moderate to Severe Canine Osteoarthritis Without Anti-inflammatory Pharmacological Support: Pilot Clinical Study.
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Cabon Q, Febre M, Gomez N, Cachon T, Pillard P, Carozzo C, Saulnier N, Robert C, Livet V, Rakic R, Plantier N, Saas P, Maddens S, and Viguier E
- Abstract
Objective: To explore the long-term safety and efficacy of canine allogeneic mesenchymal stromal cells (MSC) administered intra-articularly as single or repeated injections in appendicular joints of dogs affected by moderate to severe refractory osteoarthritis. Study Design: 22 pet dogs were recruited into a non-randomized, open and monocentric study initially administering one cellular injection. A second injection was offered after 6 months to owners if the first injection did not produce expected results. Materials and Methods: Anti-inflammatory treatment (if prescribed) was discontinued at last one week before the onset of treatment. Each injection consisted of at least 10 million viable neonatal allogeneic mesenchymal stromal cells obtained from fetal adnexa. Medical data was collected from veterinary clinical evaluations of joints up to 6 months post-injection and owner's assessment of their dog's mobility and well-being followed for a further 2 years when possible. Results: Mild, immediate self-limiting inflammatory joint reactions were observed in 5/22 joints after the first injection, and in almost all dogs having a subsequent injection. No other MSC-related adverse medical events were reported, neither during the 6 months follow up visits, nor during the long-term (2-years) safety follow up. Veterinary clinical evaluation showed a significant and durable clinical improvement (up to 6 months) following MSC administration. Eight dogs (11 joints) were re-injected 6 months apart, sustaining clinical benefits up to 1 year. Owner's global satisfaction reached 75% at 2 years post-treatment Conclusion: Our data suggest that a single or repeated intra-articular administration of neonatal MSC in dogs with moderate to severe OA is a safe procedure and confer clinical benefits over a 24-month period. When humoral response against MSC is investigated by flow cytometry, a positive mild and transient signal was detected in only one dog from the studied cohort, this dog having had a positive clinical outcome.
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- 2019
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25. Differences in the intrinsic chondrogenic potential of equine umbilical cord matrix and cord blood mesenchymal stromal/stem cells for cartilage regeneration.
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Rakic R, Bourdon B, Demoor M, Maddens S, Saulnier N, and Galéra P
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- Animals, Bone Morphogenetic Protein 2 metabolism, Cartilage metabolism, Cell Differentiation drug effects, Cells, Cultured, Chondrocytes metabolism, Chondrogenesis genetics, Collagen Type I metabolism, Extracellular Matrix chemistry, Extracellular Matrix metabolism, Fetal Blood physiology, Horses, Hyaline Cartilage metabolism, Mesenchymal Stem Cells physiology, Osteogenesis drug effects, Regeneration drug effects, Reproducibility of Results, Tissue Engineering methods, Transforming Growth Factor beta1 metabolism, Umbilical Cord physiology, Chondrogenesis physiology, Fetal Blood cytology, Umbilical Cord cytology
- Abstract
Umbilical cord blood mesenchymal stromal/stem cells (UCB-MSCs) and umbilical cord matrix MSCs (UCM-MSCs) have chondrogenic potential and are alternative sources to standard surgically derived bone marrow or adipose tissue collection for cartilage engineering. However, the majority of comparative studies explore neonatal MSCs potential only on ISCT benchmark assays accounting for some bias in the reproducibility between in vitro and in clinical studies. Therefore, we characterized equine UCB-MSCs and UCM-MSCs and investigated with particular attention their chondrogenesis potential in 3D culture with BMP-2 + TGF-ß1 in normoxia or hypoxia. We carried out an exhaustive characterization of the extracellular matrix generated by both these two types of MSCs after the induction of chondrogenesis through evaluation of hyaline cartilage, hypertrophic and osteogenic markers (mRNA, protein and histology levels). Some differences in hypoxia sensitivity and chondrogenesis were observed. UCB-MSCs differentiated into chondrocytes express an abundant, dense and a hyaline-like cartilage matrix. By contrast, despite their expression of cartilage markers, UCM-MSCs failed to express a relevant cartilage matrix after chondrogenic induction. Both MSCs types also displayed intrinsic differences at their undifferentiated basal status, UCB-MSCs expressing higher levels of chondrogenic markers whereas UCM-MSCs synthesizing higher amounts of osteogenic markers. Our results suggest that UCB-MSCs should be preferred for ex-vivo horse cartilage engineering. How those results should be translated to in vivo direct cartilage regeneration remains to be determined through dedicated study.
- Published
- 2018
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26. RNA Interference and BMP-2 Stimulation Allows Equine Chondrocytes Redifferentiation in 3D-Hypoxia Cell Culture Model: Application for Matrix-Induced Autologous Chondrocyte Implantation.
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Rakic R, Bourdon B, Hervieu M, Branly T, Legendre F, Saulnier N, Audigié F, Maddens S, Demoor M, and Galera P
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- Animals, Biomarkers, Bone Morphogenetic Protein 2 pharmacology, Cartilage, Articular cytology, Cartilage, Articular metabolism, Cell Culture Techniques, Cell Hypoxia genetics, Chondrocytes drug effects, Collagen Type I metabolism, Collagen Type III metabolism, Extracellular Matrix metabolism, Horses, Phenotype, RNA, Small Interfering genetics, Tissue Engineering, Bone Morphogenetic Protein 2 metabolism, Cell Differentiation drug effects, Cell Differentiation genetics, Chondrocytes cytology, Chondrocytes metabolism, RNA Interference
- Abstract
As in humans, osteoarthritis (OA) causes considerable economic loss to the equine industry. New hopes for cartilage repair have emerged with the matrix-associated autologous chondrocyte implantation (MACI). Nevertheless, its limitation is due to the dedifferentiation occurring during the chondrocyte amplification phase, leading to the loss of its capacity to produce a hyaline extracellular matrix (ECM). To enhance the MACI therapy efficiency, we have developed a strategy for chondrocyte redifferentiation, and demonstrated its feasibility in the equine model. Thus, to mimic the cartilage microenvironment, the equine dedifferentiated chondrocytes were cultured in type I/III collagen sponges for 7 days under hypoxia in the presence of BMP-2. In addition, chondrocytes were transfected by siRNA targeting Col1a1 and Htra1 mRNAs, which are overexpressed during dedifferentiation and OA. To investigate the quality of the neo-synthesized ECM, specific and atypical cartilage markers were evaluated by RT-qPCR and Western blot. Our results show that the combination of 3D hypoxia cell culture, BMP-2 (Bone morphogenetic protein-2), and RNA interference, increases the chondrocytes functional indexes ( Col2a1 / Col1a1 , Acan / Col1a1 ), leading to an effective chondrocyte redifferentiation. These data represent a proof of concept for this process of application, in vitro, in the equine model, and will lead to the improvement of the MACI efficiency for cartilage tissue engineering therapy in preclinical/clinical trials, both in equine and human medicine., Competing Interests: The authors declare no conflict of interest.
- Published
- 2017
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27. Evaluation of the Effect of a Single Intra-articular Injection of Allogeneic Neonatal Mesenchymal Stromal Cells Compared to Oral Non-Steroidal Anti-inflammatory Treatment on the Postoperative Musculoskeletal Status and Gait of Dogs over a 6-Month Period after Tibial Plateau Leveling Osteotomy: A Pilot Study.
- Author
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Taroni M, Cabon Q, Fèbre M, Cachon T, Saulnier N, Carozzo C, Maddens S, Labadie F, Robert C, and Viguier E
- Abstract
Objective: Compare the clinical and pressure walkway gait evolution of dogs after a tibial plateau leveling osteotomy (TPLO) for a cranial cruciate ligament rupture (CrCLR) and treatment with either a 1-month course of non-steroidal anti-inflammatory drugs (NSAIDs) or a single postoperative intra-articular (IA) injection of allogeneic neonatal mesenchymal stromal cells (MSCs)., Study Design: Prospective, double-blinded, randomized, controlled, monocentric clinical study., Animals: Sixteen client-owned dogs., Materials and Methods: Dogs with unilateral CrCLR confirmed by arthroscopy were included. Allogeneic neonatal canine MSCs were obtained from fetal adnexa retrieved after C-section performed on healthy pregnant bitches. The dogs were randomly allocated to either the "MSCs group," receiving an IA injection of MSCs after TPLO, followed by placebo for 1 month, or the "NSAIDs group," receiving IA equivalent volume of MSCs vehicle after TPLO, followed by oral NSAID for 1 month. One of the three blinded evaluators assessed the dogs in each group before and after surgery (1, 3, and 6 months). Clinical score and gait and bone healing process were assessed. The data were statistically compared between the two groups for pre- and postoperative evaluations., Results: Fourteen dogs (nine in the MSCs group, five in the NSAIDs group) completed the present study. No significant difference was observed between the groups preoperatively. No local or systemic adverse effect was observed after MSCs injection at any time point considered. At 1 month after surgery, bone healing scores were significantly higher in the MSCs group. At 1, 3, and 6 months after surgery, no significant difference was observed between the two groups for clinical scores and gait evaluation., Conclusion: A single IA injection of allogeneic neonatal MSCs could be a safe and valuable postoperative alternative to NSAIDs for dogs requiring TPLO surgery, particularly for dogs intolerant to this class of drugs.
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- 2017
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28. Gene expression profile of glioblastoma peritumoral tissue: an ex vivo study.
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Mangiola A, Saulnier N, De Bonis P, Orteschi D, Sica G, Lama G, Pettorini BL, Sabatino G, Zollino M, Lauriola L, Colabianchi A, Proietti G, Kovacs G, Maira G, and Anile C
- Subjects
- Brain metabolism, Brain Neoplasms genetics, Cell Adhesion, Cell Movement, Cell Proliferation, Cluster Analysis, Comparative Genomic Hybridization, Genome-Wide Association Study, Glioblastoma genetics, Humans, Neurons metabolism, Oligonucleotide Array Sequence Analysis, Brain pathology, Brain Neoplasms metabolism, Gene Expression Regulation, Neoplastic, Glioblastoma metabolism, Transcriptome
- Abstract
The gene expression pattern of glioblastoma (GBM) is well documented but the expression profile of brain adjacent to tumor is not yet analysed. This may help to understand the oncogenic pathway of GBM development. We have established the genome-wide expression profiles of samples isolated from GBM tumor mass, white matter adjacent to tumor (apparently free of tumor cells), and white matter controls by using the Affymetrix HG-U133 arrays. Array-CGH (aCGH) was also performed to detect genomic alterations. Among genes dysregulated in peritumoral white matter, 15 were over-expressed, while 42 were down-regulated when compared to white matter controls. A similar expression profile was detected in GBM cells. Growth, proliferation and cell motility/adhesion-associated genes were up-regulated while genes involved in neurogenesis were down-regulated. Furthermore, several tumor suppressor genes along with the KLRC1 (a member of natural killer receptor) were also down-regulated in the peritumoral brain tissue. Several mosaic genomic lesions were detected by aCGH, mostly in tumor samples and several GBM-associated mosaic genomic lesions were also present in the peritumoral brain tissue, with a similar mosaicism pattern. Our data could be explained by a dilution of genes expressed from tumor cells infiltrating the peritumour tissue. Alternatively, these findings could be substained by a relevant amount of "apparently normal" cells presenting a gene profile compatible with a precancerous state or even "quiescent" cancer cells. Otherwise, the recurrent tumor may arise from both infiltrating tumor cells and from an interaction and recruitment of apparently normal cells in the peritumor tissue by infiltrating tumor cells.
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- 2013
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29. ERK1 regulates the hematopoietic stem cell niches.
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Saulnier N, Guihard S, Holy X, Decembre E, Jurdic P, Clay D, Feuillet V, Pagès G, Pouysségur J, Porteu F, and Gaudry M
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- Animals, Bone Density, Bone Marrow pathology, Bone and Bones enzymology, Bone and Bones pathology, Cell Compartmentation, Cell Differentiation, Cell Lineage, Cell Movement, Cell Proliferation, Cellular Microenvironment, Gene Deletion, Macrophages pathology, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase 3 deficiency, Monocytes, Osteoblasts enzymology, Osteoblasts pathology, Osteoclasts enzymology, Osteoclasts pathology, Osteogenesis, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells enzymology, Mitogen-Activated Protein Kinase 3 metabolism, Stem Cell Niche
- Abstract
The mitogen-activated protein kinases (MAPK) ERK1 and ERK2 are among the major signal transduction molecules but little is known about their specific functions in vivo. ERK activity is provided by two isoforms, ERK1 and ERK2, which are ubiquitously expressed and share activators and substrates. However, there are not in vivo studies which have reported a role for ERK1 or ERK2 in HSCs and the bone marrow microenvironment. The present study shows that the ERK1-deficient mice present a mild osteopetrosis phenotype. The lodging and the homing abilities of the ERK1(-/-) HSC are impaired, suggesting that the ERK1(-/-)-defective environment may affect the engrafment of HSCs. Serial transplantations demonstrate that ERK1 is involved in the maintenance of an appropriate medullar microenvironment, but that the intrinsic properties of HSCs are not altered by the ERK1(-/-) defective microenvironment. Deletion of ERK1 impaired in vitro and in vivo osteoclastogenesis while osteoblasts were unaffected. As osteoclasts derive from precursors of the monocyte/macrophage lineage, investigation of the monocytic compartment was performed. In vivo analysis of the myeloid lineage progenitors revealed that the frequency of CMPs increased by approximately 1.3-fold, while the frequency of GMPs significantly decreased by almost 2-fold, compared with the respective WT compartments. The overall mononuclear-phagocyte lineage development was compromised in these mice due to a reduced expression of the M-CSF receptor on myeloid progenitors. These results show that the cellular targets of ERK1 are M-CSFR-responsive cells, upstream to osteoclasts. While ERK1 is well known to be activated by M-CSF, the present results are the first to point out an ERK1-dependent M-CSFR regulation on hematopoietic progenitors. This study reinforces the hypothesis of an active cross-talk between HSCs, their progeny and bone cells in the maintenance of the homeostasis of these compartments.
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- 2012
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30. Lim mineralization protein 3 induces the osteogenic differentiation of human amniotic fluid stromal cells through Kruppel-like factor-4 downregulation and further bone-specific gene expression.
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Barba M, Pirozzi F, Saulnier N, Vitali T, Natale MT, Logroscino G, Robbins PD, Gambotto A, Neri G, Michetti F, Pola E, and Lattanzi W
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- Cell Differentiation, Cells, Cultured, Down-Regulation, Female, Gene Expression Regulation, Developmental physiology, Humans, Kruppel-Like Factor 4, Osteogenesis physiology, Amniotic Fluid cytology, Intracellular Signaling Peptides and Proteins metabolism, Kruppel-Like Transcription Factors metabolism, LIM Domain Proteins metabolism, Osteoblasts cytology, Osteoblasts metabolism, Stromal Cells cytology, Stromal Cells metabolism
- Abstract
Multipotent mesenchymal stem cells with extensive self-renewal properties can be easily isolated and rapidly expanded in culture from small volumes of amniotic fluid. These cells, namely, amniotic fluid-stromal cells (AFSCs), can be regarded as an attractive source for tissue engineering purposes, being phenotypically and genetically stable, plus overcoming all the safety and ethical issues related to the use of embryonic/fetal cells. LMP3 is a novel osteoinductive molecule acting upstream to the main osteogenic pathways. This study is aimed at delineating the basic molecular events underlying LMP3-induced osteogenesis, using AFSCs as a cellular model to focus on the molecular features underlying the multipotency/differentiation switch. For this purpose, AFSCs were isolated and characterized in vitro and transfected with a defective adenoviral vector expressing the human LMP3. LMP3 induced the successful osteogenic differentiation of AFSC by inducing the expression of osteogenic markers and osteospecific transcription factors. Moreover, LMP3 induced an early repression of the Kruppel-like factor-4, implicated in MSC stemness maintenance. KLF4 repression was released upon LMP3 silencing, indicating that this event could be reasonably considered among the basic molecular events that govern the proliferation/differentiation switch during LMP3-induced osteogenic differentiation of AFSC.
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- 2012
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31. Gene profiling of bone marrow- and adipose tissue-derived stromal cells: a key role of Kruppel-like factor 4 in cell fate regulation.
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Saulnier N, Puglisi MA, Lattanzi W, Castellini L, Pani G, Leone G, Alfieri S, Michetti F, Piscaglia AC, and Gasbarrini A
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- Adult, Binding Sites, Bone Marrow Cells cytology, Cell Differentiation genetics, Chromatin Immunoprecipitation, Female, Gene Expression Regulation, Gene Knockdown Techniques, Humans, Kruppel-Like Factor 4, Kruppel-Like Transcription Factors genetics, Male, Mesenchymal Stem Cells cytology, Middle Aged, Models, Biological, Polymerase Chain Reaction, Promoter Regions, Genetic genetics, Protein Binding, Reproducibility of Results, Stromal Cells cytology, Stromal Cells metabolism, Young Adult, Adipose Tissue cytology, Bone Marrow Cells metabolism, Cell Lineage genetics, Gene Expression Profiling, Kruppel-Like Transcription Factors metabolism, Mesenchymal Stem Cells metabolism
- Abstract
Background Aims: Bone marrow- and adipose tissue-derived mesenchymal stromal cells (MSC) represent promising sources for regenerative medicine. However, the precise molecular mechanisms underlying MSC stemness maintenance versus differentiation are not fully understood. The aim of this study was to compare the genome-wide expression profiles of bone marrow-and adipose tissue-derived MSC, in order to identify a common molecular stemness core., Methods: Molecular profiling was carried out using Affymetrix microarray and relevant genes were further validated by Q-PCR., Results: We identified an overlapping dataset of 190 transcripts commonly regulated in both cell populations, which included several genes involved in stemness regulation (i.e. self-renewal potential and the ability to generate differentiated cells), various signaling pathways and transcription factors. In particular, we identified a central role of the Kruppel-like factor 4 (KLF4) DNA-binding protein in regulating MSC transcriptional activity., Conclusions: Our results provide new insights toward understanding the molecular basis of MSC stemness maintenance and underline the ability of KLF4 to maintain cells in an undifferentiated state.
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- 2011
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32. Neurotrophic features of human adipose tissue-derived stromal cells: in vitro and in vivo studies.
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Lattanzi W, Geloso MC, Saulnier N, Giannetti S, Puglisi MA, Corvino V, Gasbarrini A, and Michetti F
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- Adipose Tissue metabolism, Adult, Animals, Cell Differentiation, Cells, Cultured, Culture Media, Conditioned, Gene Expression, Gene Expression Profiling, Humans, Male, Mesenchymal Stem Cell Transplantation methods, Mesenchymal Stem Cells metabolism, Middle Aged, PC12 Cells, Primary Cell Culture, Rats, Up-Regulation, Adipose Tissue cytology, Cell Adhesion Molecules metabolism, Coculture Techniques methods, Neurites metabolism, Receptors, Nerve Growth Factor metabolism, Stromal Cells metabolism
- Abstract
Due to its abundance, easy retrieval, and plasticity characteristics, adipose-tissue-derived stromal cells (ATSCs) present unquestionable advantages over other adult-tissue-derived stem cells. Based on the in silico analysis of our previous data reporting the ATSC-specific expression profiles, the present study attempted to clarify and validate at the functional level the expression of the neurospecific genes expressed by ATSC both in vitro and in vivo. This allowed evidencing that ATSCs express neuro-specific trophins, metabolic genes, and neuroprotective molecules. They were in fact able to induce neurite outgrowth in vitro, along with tissue-specific commitment along the neural lineage and the expression of the TRKA neurotrophin receptor in vivo. Our observation adds useful information to recent evidence proposing these cells as a suitable tool for cell-based applications in neuroregenerative medicine.
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- 2011
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33. The MAPK ERK1 is a negative regulator of the adult steady-state splenic erythropoiesis.
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Guihard S, Clay D, Cocault L, Saulnier N, Opolon P, Souyri M, Pagès G, Pouysségur J, Porteu F, and Gaudry M
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- Anemia chemically induced, Animals, Apoptosis, Blotting, Western, Bone Marrow Transplantation, Bone Morphogenetic Protein 4 genetics, Bone Morphogenetic Protein 4 metabolism, Colony-Forming Units Assay, Erythroid Precursor Cells cytology, Erythropoietin metabolism, Flow Cytometry, Mice, Mice, Inbred C57BL, Oxidants toxicity, Phenylhydrazines toxicity, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, Erythropoietin genetics, Receptors, Erythropoietin metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Spleen cytology, Anemia pathology, Erythroid Precursor Cells physiology, Erythropoiesis physiology, Mitogen-Activated Protein Kinase 3 physiology, Spleen metabolism
- Abstract
The mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase 1 (ERK1) and ERK2 are among the main signal transduction molecules, but little is known about their isoform-specific functions in vivo. We have examined the role of ERK1 in adult hematopoiesis with ERK1(-/-) mice. Loss of ERK1 resulted in an enhanced splenic erythropoiesis, characterized by an accumulation of erythroid progenitors in the spleen, without any effect on the other lineages or on bone marrow erythropoiesis. This result suggests that the ablation of ERK1 induces a splenic stress erythropoiesis phenotype. However, the mice display no anemia. Deletion of ERK1 did not affect erythropoietin (EPO) serum levels or EPO/EPO receptor signaling and was not compensated by ERK2. Splenic stress erythropoiesis response has been shown to require bone morphogenetic protein 4 (BMP4)-dependent signaling in vivo and to rely on the expansion of a resident specialized population of erythroid progenitors, termed stress erythroid burst-forming units (BFU-Es). A great expansion of stress BFU-Es and increased levels of BMP4 mRNA were found in ERK1(-/-) spleens. The ERK1(-/-) phenotype can be transferred by bone marrow cells. These findings show that ERK1 controls a BMP4-dependent step, regulating the steady state of splenic erythropoiesis.
- Published
- 2010
- Full Text
- View/download PDF
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