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  1. Article ; Online: Mesenchymal Stem Cell Therapy for Bone Repair of Human Hip Osteonecrosis with Bilateral Match-Control Evaluation: Impact of Tissue Source, Cell Count, Disease Stage, and Volume Size on 908 Hips.

    Hernigou, Philippe / Homma, Yasuhiro / Hernigou, Jacques / Flouzat Lachaniette, Charles Henri / Rouard, Helène / Verrier, Sophie

    Cells

    2024  Volume 13, Issue 9

    Abstract: We investigated the impact of mesenchymal stem cell (MSC) therapy on treating bilateral human hip osteonecrosis, analyzing 908 cases. This study assesses factors such as tissue source and cell count, comparing core decompression with various cell ... ...

    Abstract We investigated the impact of mesenchymal stem cell (MSC) therapy on treating bilateral human hip osteonecrosis, analyzing 908 cases. This study assesses factors such as tissue source and cell count, comparing core decompression with various cell therapies. This research emphasizes bone repair according to pre-treatment conditions and the specificities of cell therapy in osteonecrosis repair, indicating a potential for improved bone repair strategies in hips without femoral head collapse. This study utilized a single-center retrospective analysis to investigate the efficacy of cellular approaches in the bone repair of osteonecrosis. It examined the impact on bone repair of tissue source (autologous bone marrow concentrate, allogeneic expanded, autologous expanded), cell quantity (from none in core decompression alone to millions in cell therapy), and osteonecrosis stage and volume. Excluding hips with femoral head collapse, it focused on patients who had bilateral hip osteonecrosis, both pre-operative and post-operative MRIs, and a follow-up of over five years. The analysis divided these patients into seven groups based on match control treatment variations in bilateral hip osteonecrosis, primarily investigating the outcomes between core decompression, washing effect, and different tissue sources of MSCs. Younger patients (<30 years) demonstrated significantly better repair volumes, particularly in stage II lesions, than older counterparts. Additionally, bone repair volume increased with the number of implanted MSCs up to 1,000,000, beyond which no additional benefits were observed. No significant difference was observed in repair outcomes between different sources of MSCs (BMAC, allogenic, or expanded cells). The study also highlighted that a 'washing effect' was beneficial, particularly for larger-volume osteonecrosis when combined with core decompression. Partial bone repair was the more frequent event observed, while total bone repair of osteonecrosis was rare. The volume and stage of osteonecrosis, alongside the number of injected cells, significantly affected treatment outcomes. In summary, this study provides comprehensive insights into the effectiveness and variables influencing the use of mesenchymal stem cells in treating human hip osteonecrosis. It emphasizes the potential of cell therapy while acknowledging the complexity and variability of results based on factors such as age, cell count, and disease stage.
    MeSH term(s) Humans ; Mesenchymal Stem Cell Transplantation/methods ; Male ; Female ; Adult ; Middle Aged ; Femur Head Necrosis/therapy ; Femur Head Necrosis/pathology ; Retrospective Studies ; Mesenchymal Stem Cells/cytology ; Cell Count ; Young Adult ; Aged ; Treatment Outcome ; Adolescent ; Magnetic Resonance Imaging
    Language English
    Publishing date 2024-05-01
    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/cells13090776
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: ELKS1 localizes the synaptic vesicle priming protein bMunc13-2 to a specific subset of active zones

    Opazo, Felipe / Nestvogel, Dennis / Kalla, Stefan / Verrier, Sophie / Bungers, Simon / Varoqueaux, Frederique / Gundelfinger, Eckart / Brose, Nils

    The journal of cell biology, 216(4):1143-1161

    2017  

    Abstract: Presynaptic active zones (AZs) are unique subcellular structures at neuronal synapses, which contain a network of specific proteins that control synaptic vesicle (SV) tethering, priming, and fusion. Munc13s are core AZ proteins with an essential function ...

    Institution Leibniz-Institut für Neurobiologie
    Abstract Presynaptic active zones (AZs) are unique subcellular structures at neuronal synapses, which contain a network of specific proteins that control synaptic vesicle (SV) tethering, priming, and fusion. Munc13s are core AZ proteins with an essential function in SV priming. In hippocampal neurons, two different Munc13s—Munc13-1 and bMunc13-2—mediate opposite forms of presynaptic short-term plasticity and thus differentially affect neuronal network characteristics. We found that most presynapses of cortical and hippocampal neurons contain only Munc13-1, whereas ∼10% contain both Munc13-1 and bMunc13-2. Whereas the presynaptic recruitment and activation of Munc13-1 depends on Rab3-interacting proteins (RIMs), we demonstrate here that bMunc13-2 is recruited to synapses by the AZ protein ELKS1, but not ELKS2, and that this recruitment determines basal SV priming and short-term plasticity. Thus, synapse-specific interactions of different Munc13 isoforms with ELKS1 or RIMs are key determinants of the molecular and functional heterogeneity of presynaptic AZs.
    Language English
    Document type Article
    Database Repository for Life Sciences

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  3. Article ; Online: T-cadherin is a novel regulator of pericyte function during angiogenesis.

    Dasen, Boris / Pigeot, Sebastien / Born, Gordian Manfred / Verrier, Sophie / Rivero, Olga / Dittrich, Petra S / Martin, Ivan / Filippova, Maria

    American journal of physiology. Cell physiology

    2023  Volume 324, Issue 4, Page(s) C821–C836

    Abstract: Pericytes are mural cells that play an important role in regulation of angiogenesis and endothelial function. Cadherins are a superfamily of adhesion molecules mediating ... ...

    Abstract Pericytes are mural cells that play an important role in regulation of angiogenesis and endothelial function. Cadherins are a superfamily of adhesion molecules mediating Ca
    MeSH term(s) Humans ; Pericytes/metabolism ; Endothelial Cells/metabolism ; Cadherins/genetics ; Cadherins/metabolism ; Morphogenesis ; Neovascularization, Physiologic
    Chemical Substances H-cadherin ; Cadherins
    Language English
    Publishing date 2023-02-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 392098-7
    ISSN 1522-1563 ; 0363-6143
    ISSN (online) 1522-1563
    ISSN 0363-6143
    DOI 10.1152/ajpcell.00326.2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Prognosis of hip osteonecrosis after cell therapy with a calculator and artificial intelligence: ten year collapse-free survival prediction on three thousand and twenty one hips.

    Hernigou, Philippe / Verrier, Sophie / Homma, Yasuhiro / Rouard, Hélène / Lachaniette, Charles Henri Flouzat / Sunil Kumar, Karadi Hari

    International orthopaedics

    2023  Volume 47, Issue 7, Page(s) 1689–1705

    Abstract: Purpose: Several reports have identified prognostic factors for hip osteonecrosis treated with cell therapy, but no study investigated the accuracy of artificial intelligence method such as machine learning and artificial neural network (ANN) to predict ...

    Abstract Purpose: Several reports have identified prognostic factors for hip osteonecrosis treated with cell therapy, but no study investigated the accuracy of artificial intelligence method such as machine learning and artificial neural network (ANN) to predict the efficiency of the treatment. We determined the benefit of cell therapy compared with core decompression or natural evolution, and developed machine-learning algorithms for predicting ten year collapse-free survival in hip osteonecrosis treated with cell therapy. Using the best algorithm, we propose a calculator for "prognosis hip osteonecrosis cell therapy (PHOCT)" accessible for clinical use.
    Methods: A total of 3145 patients with 5261 osteonecroses without collapses were included in this study, comprising 1321 (42%) men and 1824 (58%) women, with a median age of 34 (12-62) years. Cell therapy was the treatment for 3021 hips, core decompression alone for 1374 hips, while absence of treatment was the control group of 764 hips. First, logistic regression and binary logistic regression analysis were performed to compare results of the three groups at ten years. Then an artificial neural network model was developed for ten year collapse-free survival after cell therapy. The models' performances were compared. The algorithms were assessed by calibration, and performance, and with c-statistic as measure of discrimination. It ranges from 0.5 to 1.0, with 1.0 being perfect discrimination and 0.5 poor (no better than chance at making a prediction).
    Results: Among the 3021 hips with cell therapy, 1964 hips (65%) were collapse-free survival at ten years, versus 453 (33%) among those 1374 treated with core decompression alone, and versus 115 (15%) among 764 hips with natural evolution. We analyzed factors influencing the prediction of collapse-free period with classical statistics and artificial intelligence among hips with cell therapy. After selecting variables, a machine learning algorithm created a prognosis osteonecrosis cell therapy calculator (POCT). This calculator proved to have good accuracy on validation in these series of 3021 hip osteonecroses treated with cell therapy. The algorithm had a c-statistic of 0.871 suggesting good-to-excellent discrimination when all the osteonecroses were mixed. The c-statistics were calculated separately for subpopulations of categorical osteonecroses. It retained good accuracy, but underestimated ten year survival in some subgroups, suggesting that specific calculators could be useful for some subgroups. This study highlights the importance of multimodal evaluation of patient parameters and shows the degree to which the outcome is modified by some decisions that are within a surgeon's control, as the number of cells to aspirate, the choice of injecting in both the osteonecrosis and the healthy bone, the choice between unilateral or bilateral injection, and the possibility to do a repeat injection.
    Conclusion: Many disease conditions and the heterogeneities of patients are causes of variation of outcome after cell therapy for osteonecrosis. Predicting therapeutic effectiveness with a calculator allows a good discrimination to target patients who are most likely to benefit from this intervention.
    MeSH term(s) Male ; Humans ; Female ; Adult ; Middle Aged ; Artificial Intelligence ; Prognosis ; Osteonecrosis/therapy ; Osteonecrosis/surgery ; Hip/surgery ; Arthroplasty, Replacement, Hip ; Femur Head Necrosis/therapy ; Femur Head Necrosis/surgery ; Treatment Outcome
    Language English
    Publishing date 2023-04-10
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 80384-4
    ISSN 1432-5195 ; 0341-2695
    ISSN (online) 1432-5195
    ISSN 0341-2695
    DOI 10.1007/s00264-023-05788-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Raman Spectroscopy in Skeletal Tissue Disorders and Tissue Engineering: Present and Prospective.

    Fosca, Marco / Basoli, Valentina / Della Bella, Elena / Russo, Fabrizio / Vadalà, Gianluca / Alini, Mauro / Rau, Julietta V / Verrier, Sophie

    Tissue engineering. Part B, Reviews

    2022  Volume 28, Issue 5, Page(s) 949–965

    Abstract: Musculoskeletal disorders are the most common reason of chronic pain and disability, representing an enormous socioeconomic burden worldwide. In this review, new biomedical application fields for Raman spectroscopy (RS) technique related to skeletal ... ...

    Abstract Musculoskeletal disorders are the most common reason of chronic pain and disability, representing an enormous socioeconomic burden worldwide. In this review, new biomedical application fields for Raman spectroscopy (RS) technique related to skeletal tissues are discussed, showing that it can provide a comprehensive profile of tissue composition
    MeSH term(s) Humans ; Tissue Engineering ; Spectrum Analysis, Raman/methods ; Prospective Studies ; Cartilage ; Water
    Chemical Substances Water (059QF0KO0R)
    Language English
    Publishing date 2022-01-05
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2420584-9
    ISSN 1937-3376 ; 1937-3368
    ISSN (online) 1937-3376
    ISSN 1937-3368
    DOI 10.1089/ten.TEB.2021.0139
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book ; Online ; Thesis: Characterisation of a SNARE-complex involved in Golgi-to-ER retrograde transport in mammalian cells

    Verrier, Sophie

    2006  

    Author's details submitted by Sophie Verrier
    Language English
    Size Online-Ressource
    Document type Book ; Online ; Thesis
    Thesis / German Habilitation thesis Univ., Diss--Göttingen, 2005
    Database Former special subject collection: coastal and deep sea fishing

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  7. Article ; Online: In vitro simulation of the early proinflammatory phase in fracture healing reveals strong immunomodulatory effects of CD146-positive mesenchymal stromal cells.

    Herrmann, Marietta / Stanić, Barbara / Hildebrand, Maria / Alini, Mauro / Verrier, Sophie

    Journal of tissue engineering and regenerative medicine

    2019  Volume 13, Issue 8, Page(s) 1466–1481

    Abstract: The impact of microenvironmental cues and changes due to injury on the phenotype and fate of mesenchymal stromal cells (MSCs) is poorly understood. Here, we aimed to simulate the microenvironment associated with the early stage of bone healing in vitro ... ...

    Abstract The impact of microenvironmental cues and changes due to injury on the phenotype and fate of mesenchymal stromal cells (MSCs) is poorly understood. Here, we aimed to simulate the microenvironment associated with the early stage of bone healing in vitro and to study the regenerative response of MSCs. We enriched CD146+ MSCs from the human bone marrow. Different physiological and pathological microenvironments were simulated by using conditioned medium (CM) from human endothelial cells and osteoblasts (healthy bone), femoral head-derived bone fragments (injured bone), and activated platelets (platelet-rich plasma [PRP], injury). Cells were incubated in CM and analyzed with respect to proliferation, gene expression, migration, osteogenic differentiation, and their effect on polyclonally induced proliferation of peripheral blood mononuclear cells. CD146+ MSCs showed a specific response to different microenvironments. Cell proliferation was observed in all media with the highest values in PRP-CM and injured bone-CM. Gene expression analysis revealed the upregulation of chemokines, proinflammatory, proangiogenic, and genes involved in immunomodulation in cells stimulated with PRP- and injured bone-CM, suggesting strong paracrine activity. PRP-CM led to pronounced inhibition of lymphocyte proliferation by CD146+MSCs. Our results indicate that a microenvironment simulating bone injury elicits strong immunomodulatory and proangiogenic activity of CD146+ MSCs. This suggests that in the early stage of bone healing, the prime function of MSCs and their CD146+ subpopulation is in regulating the immune response and inducing neovascularization. Future studies will investigate the key components in CM driving this function, which might be potential targets to therapeutically stimulate the regenerative potential of MSCs.
    MeSH term(s) Bone and Bones/pathology ; CD146 Antigen/metabolism ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Cellular Microenvironment/drug effects ; Chemokines/metabolism ; Chemotactic Factors/pharmacology ; Culture Media, Conditioned/pharmacology ; Fracture Healing/drug effects ; Human Umbilical Vein Endothelial Cells/cytology ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Immunomodulation/drug effects ; Inflammation/pathology ; Lymphocytes/drug effects ; Lymphocytes/metabolism ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/drug effects ; Mesenchymal Stem Cells/immunology ; Neovascularization, Physiologic/drug effects ; Osteogenesis/drug effects ; Platelet-Rich Plasma/metabolism ; Up-Regulation/drug effects
    Chemical Substances CD146 Antigen ; Chemokines ; Chemotactic Factors ; Culture Media, Conditioned
    Language English
    Publishing date 2019-06-25
    Publishing country England
    Document type Journal Article
    ISSN 1932-7005
    ISSN (online) 1932-7005
    DOI 10.1002/term.2902
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: In Vitro Models to Mimic the Endothelial Barrier

    Barbe, Laurent / Alini, Mauro / Herrmann, Marietta / Verrier, Sophie

    ATLA. Alternatives to laboratory animals. , v. 43, no. 3

    2015  

    Abstract: Microfluidic technologies permit the replication in vitro of geometrical features essential for the homeostasis of all vascularised tissues in vivo, including the contribution of pericytes to the endothelial ... ...

    Abstract Microfluidic technologies permit the replication in vitro of geometrical features essential for the homeostasis of all vascularised tissues in vivo, including the contribution of pericytes to the endothelial barrier
    Keywords homeostasis ; laboratory animals ; microfluidic technology ; models ; tissues
    Language English
    Dates of publication 2015-07
    Size p. P34-P36.
    Publishing place SAGE Publications
    Document type Article
    ZDB-ID 605800-0
    ISSN 0261-1929
    ISSN 0261-1929
    DOI 10.1177/026119291504300314
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Strategies to Stimulate Mobilization and Homing of Endogenous Stem and Progenitor Cells for Bone Tissue Repair.

    Herrmann, Marietta / Verrier, Sophie / Alini, Mauro

    Frontiers in bioengineering and biotechnology

    2015  Volume 3, Page(s) 79

    Abstract: The gold standard for the treatment of critical-size bone defects is autologous or allogenic bone graft. This has several limitations including donor site morbidity and the restricted supply of graft material. Cell-based tissue engineering strategies ... ...

    Abstract The gold standard for the treatment of critical-size bone defects is autologous or allogenic bone graft. This has several limitations including donor site morbidity and the restricted supply of graft material. Cell-based tissue engineering strategies represent an alternative approach. Mesenchymal stem cells (MSCs) have been considered as a source of osteoprogenitor cells. More recently, focus has been placed on the use of endothelial progenitor cells (EPCs), since vascularization is a critical step in bone healing. Although many of these approaches have demonstrated effectiveness for bone regeneration, cell-based therapies require time consuming and cost-expensive in vitro cell expansion procedures. Accordingly, research is becoming increasingly focused on the homing and stimulation of native cells. The stromal cell-derived factor-1 (SDF-1) - CXCR4 axis has been shown to be critical for the recruitment of MSCs and EPCs. Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and has been targeted in many studies. Here, we present an overview of the different approaches for delivering homing factors to the defect site by absorption or incorporation to biomaterials, gene therapy, or via genetically manipulated cells. We further review strategies focusing on the stimulation of endogenous cells to support bone repair. Finally, we discuss the major challenges in the treatment of critical-size bone defects and fracture non-unions.
    Language English
    Publishing date 2015-06-02
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2015.00079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: In Vitro Models to Mimic the Endothelial Barrier.

    Barbe, Laurent / Alini, Mauro / Verrier, Sophie / Herrmann, Marietta

    Alternatives to laboratory animals : ATLA

    2015  Volume 43, Issue 3, Page(s) P34–6

    MeSH term(s) Animal Testing Alternatives ; Animals ; Endothelium, Vascular ; Microfluidics ; Models, Animal
    Language English
    Publishing date 2015-07-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 605800-0
    ISSN 0261-1929
    ISSN 0261-1929
    DOI 10.1177/026119291504300314
    Database MEDical Literature Analysis and Retrieval System OnLINE

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