المؤلفون: Maroquenne, Manon, Bourguignon, Marianne, Larochette, Nathanael, El-Hafci, Hanane, Margottin, Morgane, Potier, Esther, Logeart-Avramoglou, Delphine

المساهمون: Biologie, Bioingénierie et Bioimagerie Ostéo-articulaires (B3OA (UMR 7052 / U1271)), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Fondation de l'Avenir, France (Grant 2017-AP-RM-17-003)

المصدر: ISSN: 1550-8943 ; Stem Cell Reviews and Reports ; https://hal.science/hal-04297756Test ; Stem Cell Reviews and Reports, 2023, 19 (8), pp.2869-2885. ⟨10.1007/s12015-023-10614-1⟩.

مصطلحات موضوعية: Adipose tissue stem cells, Bone marrow mesenchymal stem cells, Bone, Tissue regeneration, innate immune response, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity

الوصف: International audience ; Adipose tissue-derived mesenchymal stem cells (ATSCs) have been used as an alternative to bone marrow-derived mesenchymal stem cells (BMSCs) for bone tissue engineering applications. The ability of ATSCs to promote new bone formation remains lower than that of BMSCs. This study aimed to investigate the mechanisms underlying osteogenicity differences between human ATSCs and BMSCs in ceramic constructs, focusing on the effects of inflammation on this process. In contrast to ATSC-containing constructs, which did not induce bone formation in an ectopic mouse model, BMSC constructs consistently did so. Gene expression analysis revealed that human BMSCs, concomitantly with host murine progenitors, differentiated into the osteogenic lineage early postimplantation. In contrast, ATSCs differentiated later, when few implanted viable cells remained post-implantation, while the host murine cells did not differentiate. Comparison of the inflammatory profile in the cell constructs indicated concomitant upregulation of some human and murine inflammatory genes in the ATSC-constructs compared to the BMSC-constructs during the first-week post-implantation. The high level of chemokine production by the ATSCs was confirmed at the gene and protein levels before implantation. The immune cell recruitment within the constructs was then explored post-implantation. Higher numbers of TRAP-/ MRC1 (CD206)+ multinucleated giant cells, NOS2+ M1, and ARG1+ M2 macrophages were present in the ATSC constructs than in the BMSC constructs. These results proved that ATSCs are a transient source of inflammatory cytokines promoting a transient immune response post-implantation; this milieu correlates with impaired osteogenic differentiation of both the implanted ATSCs and the host osteoprogenitor cells.

العلاقة: hal-04297756; https://hal.science/hal-04297756Test; https://hal.science/hal-04297756/documentTest; https://hal.science/hal-04297756/file/Article%20Delph%20ao%C3%BBt%202023%20version%20finale.pdfTest

الإتاحة: https://doi.org/10.1007/s12015-023-10614-1Test
https://hal.science/hal-04297756Test
https://hal.science/hal-04297756/documentTest
https://hal.science/hal-04297756/file/Article%20Delph%20ao%C3%BBt%202023%20version%20finale.pdfTest

المؤلفون: Papaefstathiou, Stephanos, Larochette, Nathanaël, Liste, Rosa María Villar, Potier, Esther, Petite, Herve, Vivace, Bradley, Laratta, Joseph

المساهمون: Biologie, Bioingénierie et Bioimagerie Ostéo-articulaires (B3OA (UMR 7052 / U1271)), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Complejo Hospitalario Universitario de Santiago de Compostela Saint-Jacques-de-Compostelle, Espagne (CHUS), University of Louisville, University of Missouri Columbia (Mizzou), University of Missouri System

المصدر: ISSN: 0362-2436 ; Spine ; https://hal.science/hal-03836586Test ; Spine, 2022, 47 (14), pp.1027-1035. ⟨10.1097/BRS.0000000000004317⟩.

مصطلحات موضوعية: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system

الوصف: International audience ; Study design: In vitro analysis.Objective: The aim of this study was to assess the effect of three-dimensional (3D) printing of porous titanium on human mesenchymal stem cell (hMSC) adhesion, proliferation, and osteogenic differentiation.Summary of background data: A proprietary implant using three-dimensional porous titanium (3D-pTi) that mimics trabecu-lar bone structure, roughness, porosity, and modulus of elasticity was created (Ti-LIFE technology™, Spineart SA Switzerland). Such implants may possess osteoinductive properties augmenting fusion in addition to their structural advantages. However, the ability of 3D-pTi to affect in vitro cellular proliferation and osteogenic differentiation remains undefined.Methods: Disks of 3D-pTi with a porosity of 70% to 75% and pore size of 0.9 mm were produced using additive manufacturing technology. 2D Ti6Al4V (2D-Ti) and 2D polyetheretherketone (2D-PEEK) disks were prepared using standard manufacturing process. Tissue culture plastic (TCP) served as the control surface. All discs were characterized using 2D-micros-copy, scanning electron microscopy (SEM), and x-ray micro-computed tomography. Forty thousand hMSCs were seeded on the disks and TCP and cultured for 42 days. hMSC morphology was assessed using environmental SEM and confocal imaging following phalloidin staining. hMSC proliferation was evaluated using DNA fluorescent assay. hMSC differentiation was assessed using RT-qPCR for genes involved in hMSC osteogenic differentiation and biochemical assays were performed for alkaline phosphatase activity (ALP) and calcium content.Results: 3D-pTi lead to a higher cell number as compared to 2D-Ti and 2D-PEEK at D21, D28 and D42. ALP activity of hMSCs seeded into 3D-pTi scaffolds was as high as or higher than that of hMSCs seeded onto TCP controls over all time points and consistently higher than that of hMSCs seeded onto 2D-Ti scaffolds. However, when ALP activity was normalized to protein content, no statistical differences were found between ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34935757; hal-03836586; https://hal.science/hal-03836586Test; https://hal.science/hal-03836586/documentTest; https://hal.science/hal-03836586/file/Papaefstathiou22_Titanium.pdfTest; PUBMED: 34935757

الإتاحة: https://doi.org/10.1097/BRS.0000000000004317Test
https://hal.science/hal-03836586Test
https://hal.science/hal-03836586/documentTest
https://hal.science/hal-03836586/file/Papaefstathiou22_Titanium.pdfTest

المؤلفون: Denoeud, Cyprien, Luo, Guotian, Paquet, Joseph, Boisselier, Julie, Wosinski, Pauline, Moya, Adrien, Diallo, Ahmad, Larochette, Nathanael, Marinesco, Stéphane, Meiller, Anne, Becquart, Pierre, Moussi, Hilel, Vilquin, Jean-Thomas, Logeart-Avramoglou, Delphine, Gand, Adeline, Larreta-Garde, Véronique, Pauthe, Emmanuel, Potier, Esther, Petite, Hervé

المصدر: Communications Biology; 11/21/2023, Vol. 6 Issue 1, p1-11, 11p

مستخلص: Culture-adapted human mesenchymal stromal cells (hMSCs) are appealing candidates for regenerative medicine applications. However, these cells implanted in lesions as single cells or tissue constructs encounter an ischemic microenvironment responsible for their massive death post-transplantation, a major roadblock to successful clinical therapies. We hereby propose a paradigm shift for enhancing hMSC survival by designing, developing, and testing an enzyme-controlled, nutritive hydrogel with an inbuilt glucose delivery system for the first time. This hydrogel, composed of fibrin, starch (a polymer of glucose), and amyloglucosidase (AMG, an enzyme that hydrolyze glucose from starch), provides physiological glucose levels to fuel hMSCs via glycolysis. hMSCs loaded in these hydrogels and exposed to near anoxia (0.1% pO2) in vitro exhibited improved cell viability and angioinductive functions for up to 14 days. Most importantly, these nutritive hydrogels promoted hMSC viability and paracrine functions when implanted ectopically. Our findings suggest that local glucose delivery via the proposed nutritive hydrogel can be an efficient approach to improve hMSC-based therapeutic efficacy.A nutritive hydrogel enhances the survival of human mesenchymal stromal cells by providing physiological glucose levels in a controlled manner, eliciting new blood vessel formation in vivo. [ABSTRACT FROM AUTHOR]

: Copyright of Communications Biology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Khamsing, Dany, Lebrun, Solène, Fanget, Isabelle, Larochette, Nathanaël, Tourain, Christophe, de Sars, Vincent, Brunstein, Maia, Oheim, Martin, Carrel, Damien, Darchen, François, Desnos, Claire

المساهمون: Saints-Pères Paris Institute for Neurosciences (SPPIN - UMR 8003), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Biologie, Bioingénierie et Bioimagerie Ostéo-articulaires (B3OA (UMR 7052 / U1271)), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

المصدر: ISSN: 1756-6606 ; Molecular Brain ; https://hal.science/hal-03453450Test ; Molecular Brain, 2021, 14 (1), pp.112. ⟨10.1186/s13041-021-00820-8⟩.

مصطلحات موضوعية: mTOR, Endo-lysosomes, NMDA receptors, BDNF, Synaptic plasticity, Optogenetics, [SDV.BC]Life Sciences [q-bio]/Cellular Biology

الوصف: International audience ; Abstract Memory and long term potentiation require de novo protein synthesis. A key regulator of this process is mTORC1, a complex comprising the mTOR kinase. Growth factors activate mTORC1 via a pathway involving PI3-kinase, Akt, the TSC complex and the GTPase Rheb. In non-neuronal cells, translocation of mTORC1 to late endocytic compartments (LEs), where Rheb is enriched, is triggered by amino acids. However, the regulation of mTORC1 in neurons remains unclear. In mouse hippocampal neurons, we observed that BDNF and treatments activating NMDA receptors trigger a robust increase in mTORC1 activity. NMDA receptors activation induced a significant recruitment of mTOR onto lysosomes even in the absence of external amino acids, whereas mTORC1 was evenly distributed in neurons under resting conditions. NMDA receptor-induced mTOR translocation to LEs was partly dependent on the BDNF receptor TrkB, suggesting that BDNF contributes to the effect of NMDA receptors on mTORC1 translocation. In addition, the combination of Rheb overexpression and artificial mTORC1 targeting to LEs by means of a modified component of mTORC1 fused with a LE-targeting motif strongly activated mTOR. To gain spatial and temporal control over mTOR localization, we designed an optogenetic module based on light-sensitive dimerizers able to recruit mTOR on LEs. In cells expressing this optogenetic tool, mTOR was translocated to LEs upon photoactivation. In the absence of growth factor, this was not sufficient to activate mTORC1. In contrast, mTORC1 was potently activated by a combination of BDNF and photoactivation. The data demonstrate that two important triggers of synaptic plasticity, BDNF and NMDA receptors, synergistically power the two arms of the mTORC1 activation mechanism, i.e., mTORC1 translocation to LEs and Rheb activation. Moreover, they unmask a functional link between NMDA receptors and mTORC1 that could underlie the changes in the synaptic proteome associated with long-lasting changes in synaptic strength.

العلاقة: hal-03453450; https://hal.science/hal-03453450Test; https://hal.science/hal-03453450/documentTest; https://hal.science/hal-03453450/file/2021%20Khamsing%20Mol%20Brain%20mTOR.pdfTest

الإتاحة: https://doi.org/10.1186/s13041-021-00820-8Test
https://hal.science/hal-03453450Test
https://hal.science/hal-03453450/documentTest
https://hal.science/hal-03453450/file/2021%20Khamsing%20Mol%20Brain%20mTOR.pdfTest

المؤلفون: Larochette, Nathanael, El-Hafci, Hanane, Potier, Esther, Setterblad, Niclas, Bensidhoum, Morad, Petite, Hervé, Logeart-Avramoglou, Delphine

المساهمون: Biologie, Bioingénierie et Bioimagerie Ostéo-articulaires (B3OA (UMR 7052 / U1271)), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité)

المصدر: ACTA BIOMATERIALIA ; https://u-paris.hal.science/hal-03077271Test ; ACTA BIOMATERIALIA, 2020, 116, pp.186-200. ⟨10.1016/j.actbio.2020.09.003⟩

مصطلحات موضوعية: dissemin, [SDV]Life Sciences [q-bio], [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, [SDV.BIO]Life Sciences [q-bio]/Biotechnology

الوصف: International audience ; While human bone morphogenetic protein-2 (BMP-2) is a promising growth factor for bone regeneration, a major challenge in biomedical applications is finding an optimal carrier for its delivery at the site of injury. Because of their natural affinities for growth factors (including BMP-2) as well as their role in instructing cell function, cultured cell-derived extracellular matrices (ECM) are of special interest. We hereby hypothesized that a “bony matrix” containing mineralized, osteogenic ECM is a potential efficacious carrier of BMP-2 for promoting bone formation and, therefore, compared the efficacy of the decellularized ECM derived from osteogenic-differentiated human mesenchymal stem cells (hMSCs) to the one obtained from ECM from undifferentiated hMSCs. Our results provided evidence that both ECMs can bind BMP-2 and promote bone formation when implanted ectopically in mice. The osteoinductive potential of BMP-2, however, was greater when loaded within an osteogenic MSC-derived ECM; this outcome was correlated with higher sequestration capacity of BMP-2 over time in vivo. Interestingly, although the BMP-2 mainly bound onto the mineral crystals contained within the osteogenic MSC derived-ECM, these mineral components were not involved in the observed higher osteoinductivity, suggesting that the organic components were the critical components for the matrix efficacy as BMP-2 carrier.

العلاقة: hal-03077271; https://u-paris.hal.science/hal-03077271Test; https://u-paris.hal.science/hal-03077271/documentTest; https://u-paris.hal.science/hal-03077271/file/article.pdfTest

الإتاحة: https://doi.org/10.1016/j.actbio.2020.09.003Test
https://u-paris.hal.science/hal-03077271Test
https://u-paris.hal.science/hal-03077271/documentTest
https://u-paris.hal.science/hal-03077271/file/article.pdfTest

المؤلفون: Luo, Guotian, Denoeud, Cyprien, Larochette, Nathanael, Potier, Esther, Petite, Hervé

المصدر: Bone Reports ; volume 13, page 100372 ; ISSN 2352-1872

مصطلحات موضوعية: Orthopedics and Sports Medicine, Endocrinology, Diabetes and Metabolism

الإتاحة: https://doi.org/10.1016/j.bonr.2020.100372Test
https://api.elsevier.com/content/article/PII:S2352187220301327?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2352187220301327?httpAccept=text/plainTest

المؤلفون: Damia, Chantal, Marchat, David, Lemoine, Charly, Douard, Nathalie, Chaleix, Vincent, Sol, Vincent, Larochette, Nathanael, Logeart-Avramoglou, Delphine, Brie, Joël, Champion, Eric

المساهمون: IRCER - Axe 4 : céramiques sous contraintes environnementales (IRCER-AXE4), Institut de Recherche sur les CERamiques (IRCER), Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom Paris (IMT)-Institut Mines-Télécom Paris (IMT), Laboratoire de Chimie des Substances Naturelles (LCSN), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Bioingénierie et Bioimagerie Ostéo-articulaires, Biomécanique et Biomatériaux Ostéo-Articulaires (B2OA (UMR_7052)), École nationale vétérinaire d'Alfort (ENVA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie maxillo-faciale, réparatrice et stomatologie CHU Limoges, CHU Limoges, ANR-10-LABX-0074,Sigma-LIM,From specific ceramic materials and components to integrated, secured and intelligent communication systems(2010)

المصدر: ISSN: 0928-4931.

مصطلحات موضوعية: Silicate-substituted hydroxyapatite, Sphere elaboration, Surface functionalization, BMP-2, [CHIM.MATE]Chemical Sciences/Material chemistry, [SPI.MAT]Engineering Sciences [physics]/Materials

الوصف: International audience ; This work is devoted to the processing of bone morphogenetic protein (BMP-2) functionalized silicate substituted hydroxyapatite (SiHA) ceramic spheres. The motivation behind it is to develop injectable hydrogel/bioceramic composites for bone reconstruction applications. SiHA microspheres were shaped by spray drying and thoroughly characterized. The silicate substitution was used to provide preferred chemical sites at the ceramic surface for the covalent immobilization of BMP-2. In order to control the density and the release of the immobilized BMP-2, its grafting was performed via ethoxysilanes and polyethylene glycols. A method based on Kaiser's test was used to quantify the free amino groups of grafted organosilanes available at the ceramic surface for BMP-2 immobilization. The SiHA surface modification was investigated by means of X-ray photoelectron spectroscopy, Fourier transformed infrared spectroscopy and thermogravimetry coupled with mass spectrometry. The BMP-2 bioactivity was assessed, in vitro, by measuring the luciferase expression of a stably transfected C3H10 cell line (C3H10-BRE/Luc cells). The results provided evidence that the BMP-2 grafted onto SiHA spheres remained bioactive.

العلاقة: hal-02080103; https://unilim.hal.science/hal-02080103Test; https://unilim.hal.science/hal-02080103/documentTest; https://unilim.hal.science/hal-02080103/file/Damia%202019.pdfTest

الإتاحة: https://doi.org/10.1016/j.msec.2018.01.008Test
https://unilim.hal.science/hal-02080103Test
https://unilim.hal.science/hal-02080103/documentTest
https://unilim.hal.science/hal-02080103/file/Damia%202019.pdfTest

المؤلفون: Decambron, Adeline, Devriendt, Nausikaa, Larochette, Nathanael, Manaserro, Mathieu, Bourguignon, Marianne, El-Hafci, Hanane, Petite, Hervé, Viateau, Véronique, Logeart-Avramoglou, Delphine

المساهمون: Bioingénierie et Bioimagerie Ostéo-articulaires, Biomécanique et Biomatériaux Ostéo-Articulaires (B2OA (UMR_7052)), École nationale vétérinaire d'Alfort (ENVA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), École nationale vétérinaire d'Alfort (ENVA)

المصدر: ISSN: 1937-3341 ; EISSN: 1937-335X.

مصطلحات موضوعية: bone, tissue engineering, in vivo, BMP-2, MSC, dual delivery, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, [SDV.BIO]Life Sciences [q-bio]/Biotechnology

الوصف: International audience ; The addition of bone morphogenetic protein-2 (BMP-2) with multipotent stromal cells (MSC) is an attractive strategy to enhance the bone-forming potential of MSC-based tissue engineering (TE) constructs. However, the effective dosage of BMP-2 remains to be determined. In this study, we evaluated the effects of human MSCs codelivered with BMP-2 at either low or high dosage on the bone-forming potential of constructs in a mice ectopic model. Our results showed that the addition of only low dose of BMP-2 was beneficial to enhance the bone-forming potential of MSCs, whereas high dose of BMP-2 overcame the advantage of combining this growth factor with MSCs. Expressions of select genes of both murine and human origins in TE constructs demonstrated that the beneficial effect of low dose of BMP-2 with implanted human MSCs did not involve enhanced differentiation of these cells into osteoblasts or induction of paracrine cues but rather involved induction of the osteogenic differentiation of the host progenitors. Therefore, the advantage of combining BMP-2 with MSCs to enhance the bone-forming potential of TE constructs appeared to be an additive effect of both components rather than a synergistic one.

العلاقة: hal-02368370; https://u-paris.hal.science/hal-02368370Test; https://u-paris.hal.science/hal-02368370/documentTest; https://u-paris.hal.science/hal-02368370/file/Decambron%20et%20al%20TE%202019.pdfTest

الإتاحة: https://doi.org/10.1089/ten.TEA.2018.0146Test
https://u-paris.hal.science/hal-02368370Test
https://u-paris.hal.science/hal-02368370/documentTest
https://u-paris.hal.science/hal-02368370/file/Decambron%20et%20al%20TE%202019.pdfTest

المؤلفون: Moya, Adrien, Larochette, Nathanael, Bourguignon, Marianne, El-Hafci, Hanane, Potier, Esther, Petite, Hervé, Logeart-Avramoglou, Delphine

المساهمون: Bioingénierie et Bioimagerie Ostéo-articulaires, Biomécanique et Biomatériaux Ostéo-Articulaires (B2OA (UMR_7052)), École nationale vétérinaire d'Alfort (ENVA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

المصدر: ISSN: 1932-7005.

مصطلحات موضوعية: adipogenesis, bone, MSC, osteogenesis, predifferentiation, tissue-engineering, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, [SDV.BIO]Life Sciences [q-bio]/Biotechnology

الوصف: International audience ; In the present study, we evaluated the benefits of an adipogenic predifferentiation, the pathway most closely related to osteoblastogenesis, on the pro-osteogenic potential of human adult multipotent bone marrow stromal cells (hBMSCs), both in vitro and in vivo. Adipogenic differentiation of hBMSCs for 14 days resulted in a heterogeneous cell population from which the most adipogenic-committed cells were eliminated by their lack of readhesion ability. Our results provided evidence that the select adherent adipogenic differentiated hBMSCs (sAD+ cells) express a gene profile characteristic of both adipogenic and osteogenic lineages. In vitro, when cultured in osteogenic medium, sAD+ differentiated along the osteogenic lineage faster than undifferentiated hBMSCs. In vivo, in an ectopic mouse model, sAD+ exhibited a significantly higher bone formation capability compared with undifferentiated hBMSCs. We sought, then, to investigate the underlying mechanisms responsible for such beneficial effects of adipogenic predifferentiation on bone formation and found that this outcome was not linked to a better cell survival post-implantation. The secretome of sAD+ was both proangiogenic and chemoattractant, but its potential did not supersede the one of undifferentiated hBMSCs. However, using co-culture systems, we observed that the sAD+ paracrine factors were pro-osteogenic on undifferentiated hBMSCs. In conclusion, adipogenic priming endows hBMSCs with high osteogenic potential as well as pro-osteogenic paracrine-mediated activity. This preconditioning appears as a promising strategy for bone tissue engineering technology in order to improve the hBMSC osteogenic potency in vivo.

العلاقة: hal-02368382; https://u-paris.hal.science/hal-02368382Test; https://u-paris.hal.science/hal-02368382/documentTest; https://u-paris.hal.science/hal-02368382/file/Moya%20et%20al%20JTERM%20%281%29.pdfTest

الإتاحة: https://doi.org/10.1002/term.2571Test
https://u-paris.hal.science/hal-02368382Test
https://u-paris.hal.science/hal-02368382/documentTest
https://u-paris.hal.science/hal-02368382/file/Moya%20et%20al%20JTERM%20%281%29.pdfTest

المؤلفون: Oudina, Karim, Paquet, Joseph, Moya, Adrien, Massourides, Emmanuelle, Bensidhoum, Morad, Larochette, Nathanaël, Deschepper, Mickael, Pinset, Christian, Petite, Hervé

المصدر: Scientific Reports ; volume 8, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: Use of human induced pluripotent stem cells (h-iPSCs) for bone tissue engineering is most appealing, because h-iPSCs are an inexhaustible source of osteocompetent cells. The present study investigated the contribution of undifferentiated h-iPSCs and elucidated aspects of the underlying mechanism(s) of the involvement of these cells to new bone formation. Implantation of undifferentiated h-iPSCs seeded on coral particles in ectopic sites of mice resulted in expression of osteocalcin and DMP-1, and in mineral content similar to that of the murine bone. The number of the implanted h-iPSCs decreased with time and disappeared by 30 days post-implantation. In contrast, expression of the murine osteogenic genes at day 15 and 30 post-implantation provided, for the first time, evidence that the implanted h-iPSCs affected the observed outcomes via paracrine mechanisms. Supporting evidence was provided because supernatant conditioned media from h-iPSCs (h-iPSC CM), promoted the osteogenic differentiation of human mesenchymal stem cells (h-MSCs) in vitro . Specifically, h-iPSC CM induced upregulation of the BMP-2, BMP-4 and BMP-6 genes, and promoted mineralization of the extracellular matrix. Given the current interest in the use of h-iPSCs for regenerative medicine applications, our study contributes new insights into aspects of the mechanism underlying the bone promoting capability of h-iPSCs.

الإتاحة: https://doi.org/10.1038/s41598-018-35546-6Test
https://www.nature.com/articles/s41598-018-35546-6.pdfTest
https://www.nature.com/articles/s41598-018-35546-6Test