Effects of gamma irradiation on the biomechanical properties of peroneus tendons

PURPOSE: This study was designed to investigate the biomechanical properties of nonirradiated (NI) and irradiated (IR) peroneus tendons to determine if they would be suitable allografts, in regards to biomechanical properties, for anterior cruciate ligament reconstruction after a dose of 1.5–2.5 Mrad. METHODS: Seven pairs of peroneus longus (PL) and ten pairs of peroneus brevis (PB) tendons were procured from human cadavers. The diameter of each allograft was measured. The left side of each allograft was IR at 1.5–2.5 Mrad, whereas the right side was kept aseptic and NI. The allografts were thawed, kept wet with saline, and attached in a single-strand fashion to custom freeze grips using liquid nitrogen. A preload of 10 N was then applied and, after it had reached steady state, the allografts were pulled at 4 cm/sec. The parameters recorded were the displacement and force. RESULTS: The elongation at the peak load was 10.3±2.3 mm for the PB NI side and 13.5±3.3 mm for the PB IR side. The elongation at the peak load was 17.4±5.3 mm for the PL NI side and 16.3±2.0 mm for the PL IR side. For PL, the ultimate load was 2,091.6±148.7 N for NI and 2,122.8±380.0 N for IR. The ultimate load for the PB tendons was 1,485.7±209.3 N for NI and 1,318.4±296.9 N for the IR group. The ultimate stress calculations for PL were 90.3±11.3 MPa for NI and 94.8±21.0 MPa for IR. For the PB, the ultimate stress was 82.4±19.0 MPa for NI and 72.5±16.6 MPa for the IR group. The structural stiffness was 216.1±59.0 N/mm for the NI PL and 195.7±51.4 N/mm for the IR side. None of these measures were significantly different between the NI and IR groups. The structural stiffness was 232.1±45.7 N/mm for the NI PB and 161.9±74.0 N/mm for the IR side, and this was the only statistically significant difference found in this study (P=0.034). CONCLUSION: Our statistical comparisons found no significant differences in terms of elongation, ultimate load, or ultimate stress between IR and NI PB and PL tendons. Only the PB structural stiffness was affected by irradiation. Thus, sterilizing allografts at 1.5–2.5 Mrad of gamma irradiation does not cause major alterations in the tendons’ biomechanical properties while still providing a suitable amount of sterilization for anterior cruciate ligament reconstruction

Cellules stromales mésenchymateuses et vecteurs polymériques pour l'ingénierie tissulaire du système nerveux central

Mesenchymal stromal cells (MSCs) have several advantages for brain cell therapy. We first demonstrated that MSCs do not migrate in healthy rat brains whereas they were attracted by a lesion located far from their implantation site. However, we also confirmed that the poor cell survival and neuronal differentiation are the major obstacles encountered for brain cell therapy. Thus, we then focused on enhancing the neuronal differentiation potential of MSCs before transplantation, using an epidermal growth factor-basic fibroblast growth factor (EGF-bFGF) pre-treatment in vitro. Finally, we associated MSCs to polymeric vectors, the pharmacologically active microcarriers (PAMs), to increase cell survival and neuronal differentiation, and thereby favouring MSC tissue regeneration potential after transplantation. These PLGA microspheres were coated with a biomimetic surface of laminin, after demonstrating the benefits of this molecule on the neuronal differentiation potential of MSCs in vitro. After attachment of MSCs on their surface, neurotrophin releasing, laminin-coated PAMs have been evaluated in a rat model of Parkinson's disease. A significant functional recovery was observed compared to cells grafted without PAMs. This strategy is the first to give the proof of concept for the use of adult stem cells combined to bioactive polymeric vectors to protect the central nervous system in the context of Parkinson's disease.Les cellules stromales mésenchymateuses (CSM) possèdent de nombreux atouts pour la thérapie cellulaire du cerveau. Nous avons tout d'abord démontré que les CSM ne migraient pas dans le cerveau de rats sains alors qu'elles étaient attirées par une lésion située à grande distance de leur site d'implantation. Nous avons également confirmé que la faible survie et différenciation neuronale des cellules in vivo constituent les obstacles majeurs à la thérapie cellulaire du cerveau. Par conséquent, nous nous sommes ensuite attachés à améliorer le potentiel de différenciation neuronal des CSM avant transplantation, à l'aide d'un pré-traitement en « epidermal growth factor » (EGF) et « basic fibroblast growth factor » (bFGF) in vitro. Finalement, nous avons associé des CSM à des vecteurs polymériques, les microcarriers pharmacologiquement actifs (MPA), afin de favoriser la survie, la différenciation neuronale et les capacités de réparation tissulaire des cellules après transplantation. Ces microsphères de PLGA ont ainsi été enrobées d'une surface biomimétique de laminine, après en avoir démontré les bénéfices sur la différenciation neuronale des CSM in vitro. Des CSM ont ensuite été mises en contact avec des MPA enrobées de laminine et libérant une neurotrophine, avant transplantation dans un modèle animal de la maladie de Parkinson. D'importants effets fonctionnels ont été observés par rapport à la greffe de cellules seules, et cette stratégie est la première à démontrer l'intérêt de cellules souches adultes associées à des vecteurs polymériques bioactifs pour protéger le système nerveux central dans le contexte de la maladie de Parkinson

Cellules stromales mésenchymateuses et vecteurs polymériques pour l'ingénierie tissulaire du système nerveux central

Les cellules stromales mésenchymateuses (CSM) possèdent de nombreux atouts pour la thérapie cellulaire du cerveau. Nous avons tout d'abord démontré que les CSM ne migraient pas dans le cerveau de rats sains alors qu'elles étaient attirées par une lésion située à grande distance de leur site d'implantation. Nous avons également confirmé que la faible survie et différenciation neuronale des cellules in vivo constituent les obstacles majeurs à la thérapie cellulaire du cerveau. Par conséquent, nous nous sommes ensuite attachés à améliorer le potentiel de différenciation neuronal des CSM avant transplantation, à l'aide d'un pré-traitement en epidermal growth factor (EGF) et basic fibroblast growth factor (bFGF) in vitro. Finalement, nous avons associé des CSM à des vecteurs polymériques, les microcarriers pharmacologiquement actifs (MPA), afin de favoriser la survie, la différenciation neuronale et les capacités de réparation tissulaire des cellules après transplantation. Ces microsphères de PLGA ont ainsi été enrobées d'une surface biomimétique de laminine, après en avoir démontré les bénéfices sur la différenciation neuronale des CSM in vitro. Des CSM ont ensuite été mises en contact avec des MPA enrobées de laminine et libérant une neurotrophine, avant transplantation dans un modèle animal de la maladie de Parkinson. D'importants effets fonctionnels ont été observés par rapport à la greffe de cellules seules, et cette stratégie est la première à démontrer l'intérêt de cellules souches adultes associées à des vecteurs polymériques bioactifs pour protéger le système nerveux central dans le contexte de la maladie de Parkinson.Mesenchymal stromal cells (MSCs) have several advantages for brain cell therapy. We first demonstrated that MSCs do not migrate in healthy rat brains whereas they were attracted by a lesion located far from their implantation site. However, we also confirmed that the poor cell survival and neuronal differentiation are the major obstacles encountered for brain cell therapy. Thus, we then focused on enhancing the neuronal differentiation potential of MSCs before transplantation, using an epidermal growth factor-basic fibroblast growth factor (EGF-bFGF) pre-treatment in vitro. Finally, we associated MSCs to polymeric vectors, the pharmacologically active microcarriers (PAMs), to increase cell survival and neuronal differentiation, and thereby favouring MSC tissue regeneration potential after transplantation. These PLGA microspheres were coated with a biomimetic surface of laminin, after demonstrating the benefits of this molecule on the neuronal differentiation potential of MSCs in vitro. After attachment of MSCs on their surface, neurotrophin releasing, laminin-coated PAMs have been evaluated in a rat model of Parkinson's disease. A significant functional recovery was observed compared to cells grafted without PAMs. This strategy is the first to give the proof of concept for the use of adult stem cells combined to bioactive polymeric vectors to protect the central nervous system in the context of Parkinson's disease.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Basivertebral nerve ablation for the treatment of chronic low back pain in a community practice setting: 6 Months follow-up.

BACKGROUND: Strong innervation of the vertebral endplates by the basivertebral nerve makes it an ideal target for ablation in the treatment of vertebrogenic low back pain with Modic changes. This data represents the clinical outcomes for 16 consecutively treated patients in a community practice setting. METHODS: Basivertebral nerve ablations were performed on 16 consecutive patients by a single surgeon (WS) utilizing the INTRACEPT® device (Relievant Medsystems, Inc.). Evaluations were performed at baseline, 1 month, 3 months, and 6 months. The Oswestry Disability Index (ODI), Visual Analog Scale (VAS), and SF-36 were recorded in Medrio electronic data capture software. All patients ( RESULTS: The ODI, VAS, and SF-36 Pain Component Summary showed statistically significant improvements above minimal clinically important differences at 1 month, 3 months, and 6 months (all p values CONCLUSIONS: Basivertebral nerve ablation appears to be a durable, minimally invasive treatment for the relief of chronic low back pain that can be successfully implemented in a community practice setting. To our knowledge, this is the first independently funded US study on basivertebral nerve ablation

A Combinatorial Cell and Drug Delivery Strategy for Huntington's Disease Using Pharmacologically Active Microcarriers and RNAi Neuronally-Committed Mesenchymal Stromal Cells

International audienceFor Huntington's disease (HD) cell-based therapy, the transplanted cells are required to be committed to a neuronal cell lineage, survive and maintain this phenotype to ensure their safe transplantation in the brain. We first investigated the role of RE-1 silencing transcription factor (REST) inhibition using siRNA in the GABAergic differentiation of marrow-isolated adult multilineage inducible (MIAMI) cells, a subpopulation of MSCs. We further combined these cells to laminin-coated poly(lactic-co-glycolic acid) PLGA pharmacologically active microcarriers (PAMs) delivering BDNF in a controlled fashion to stimulate the survival and maintain the differentiation of the cells. The PAMs/cells complexes were then transplanted in an ex vivo model of HD. Using Sonic Hedgehog (SHH) and siREST, we obtained GABAergic progenitors/neuronal-like cells, which were able to secrete HGF, SDF1 VEGFa and BDNF, of importance for HD. GABA-like progenitors adhered to PAMs increased their mRNA expression of NGF/VEGFa as well as their secretion of PIGF-1, which can enhance reparative angiogenesis. In our ex vivo model of HD, they were successfully transplanted while attached to PAMs and were able to survive and maintain this GABAergic neuronal phenotype. Together, our results may pave the way for future research that could improve the success of cell-based therapy for HDs

The therapeutic potential of human multipotent mesenchymal stromal cells combined with pharmacologically active microcarriers transplanted in hemi-parkinsonian rats.: PAMs and MIAMI cells for Parkinson's disease

International audienceMultipotent mesenchymal stromal cells (MSCs) raise great interest for brain cell therapy due to their ease of isolation from bone marrow, their immunomodulatory and tissue repair capacities, their ability to differentiate into neuronal-like cells and to secrete a variety of growth factors and chemokines. In this study, we assessed the effects of a subpopulation of human MSCs, the marrow-isolated adult multilineage inducible (MIAMI) cells, combined with pharmacologically active microcarriers (PAMs) in a rat model of Parkinson's disease (PD). PAMs are biodegradable and non-cytotoxic poly(lactic-co-glycolic acid) microspheres, coated by a biomimetic surface and releasing a therapeutic protein, which acts on the cells conveyed on their surface and on their microenvironment. In this study, PAMs were coated with laminin and designed to release neurotrophin 3 (NT3), which stimulate the neuronal-like differentiation of MIAMI cells and promote neuronal survival. After adhesion of dopaminergic-induced (DI)-MIAMI cells to PAMs in vitro, the complexes were grafted in the partially dopaminergic-deafferented striatum of rats which led to a strong reduction of the amphetamine-induced rotational behavior together with the protection/repair of the nigrostriatal pathway. These effects were correlated with the increased survival of DI-MIAMI cells that secreted a wide range of growth factors and chemokines. Moreover, the observed increased expression of tyrosine hydroxylase by cells transplanted with PAMs may contribute to this functional recovery

EGFR siRNA lipid nanocapsules showed efficient in vitro transfection and growth inhibition of glioma cells

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Stratégie d'inhibition de eGFR vis des nanocapsules lipidiques de siRNA et impact sur les cellules de gliome humain U87MG

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