1. |
- Brohlin, Maria, et al.
(författare)
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Characterisation of human mesenchymal stem cells following differentiation into Schwann cell-like cells
- 2009
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Ingår i: Neuroscience research. - : Elsevier BV. - 0168-0102 .- 1872-8111. ; 64:1, s. 41-49
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Tidskriftsartikel (refereegranskat)abstract
- Cell-based therapies provide a clinically applicable and available alternative to nerve autografts. Our previous studies have characterised rat-derived mesenchymal stem cells (MSC) and here we have investigated the phenotypic, molecular and functional characteristics of human-derived MSC (hMSC) differentiated along a Schwann cell lineage. The hMSC were isolated from healthy human donors and the identity of the undifferentiated hMSC was confirmed by the detection of MSC specific cells surface markers. The hMSC were differentiated along a glial cell lineage using an established cocktail of growth factors including glial growth factor-2. Following differentiation, the hMSC expressed the key Schwann cell (SC) markers at both the transcriptional and translational level. More importantly, we show the functional effect of hMSC on neurite outgrowth using an in vitro co-culture model system with rat-derived primary sensory neurons. The number of DRG sprouting neurites was significantly enhanced in the presence of differentiated hMSC; neurite length and density (branching) were also increased. These results provide evidence that hMSC can undergo molecular, morphological and functional changes to adopt a SC-like behaviour and, therefore, could be suitable as SC substitutes for nerve repair in clinical applications.
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2. |
- Jivan, Sharmila, et al.
(författare)
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The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats.
- 2006
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Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 170:2, s. 245-254
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Tidskriftsartikel (refereegranskat)abstract
- It has been proposed clinically that delayed surgery after traumatic brachial plexus injury may adversely affect functional outcome. In the present experimental study the neuroprotective and growth-promoting effects of early and delayed nerve grafting following proximal seventh cervical spinal nerve (C7) axotomy were examined. The ventral branch of C7 spinal nerve was transected and axons projecting out of the proximal nerve stump were labelled with Fast Blue (FB). At the same time, the biceps brachii muscle was denervated by transecting the musculocutaneous nerve at its origin. Neuronal survival and muscle atrophy were then assessed at 1, 4, 8 and 16 weeks after permanent axotomy. In the experimental groups, a peripheral nerve graft was interposed between the transected C7 spinal nerve and the distal stump of the musculocutaneous nerve at 1 week [early nerve repair (ENR)] or 8 weeks [delayed nerve repair (DNR)] after axotomy. Sixteen weeks after nerve repair had been performed, a second tracer Fluoro-Ruby (FR) was applied distal to the graft to assess the efficacy of axonal regeneration. Counts of FB-labelled neurons revealed that axotomy did not induce any significant cell loss at 4 weeks, but 15% of motoneurons and 32% of sensory neurons died at 8 weeks after injury. At 16 weeks, the amount of cell loss in spinal cord and dorsal root ganglion (DRG) reached 29 and 50%, respectively. Both ENR and DNR prevented retrograde degeneration of spinal motoneurons and counteracted muscle atrophy, but failed to rescue sensory neurons. Due to substantial cell loss at 8 weeks, the number of FR-labelled neurons after DNR was significantly lower when compared to ENR. However, the proportion of regenerating neurons among surviving motoneurons and DRG neurons remained relatively constant indicating that neurons retained their regenerative capacity after prolonged axotomy. The results demonstrate that DNR could protect spinal motoneurons and reduce muscle atrophy, but had little effect on sensory DRG neurons. However, the efficacy of neuroprotection and axonal regeneration will be significantly affected by the amount of cell loss already presented at the time of nerve repair.
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3. |
- Novikova, Liudmila N, et al.
(författare)
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Alginate hydrogel and matrigel as potential cell carriers for neurotransplantation.
- 2006
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Ingår i: Journal of Biomedical Materials Research part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 77:2, s. 242-252
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Tidskriftsartikel (refereegranskat)abstract
- Development of biosynthetic conduits carrying extracellular matrix molecules and cell lines expressing neurotrophic growth factors represents a novel and promising strategy for spinal cord and peripheral nerve repair. In the present in vitro study, the compatibility and growth-promoting effects of (i) alginate hydrogel, (ii) alginate hydrogel complemented with fibronectin, and (iii) matrigel were compared between olfactory ensheathing cells (OECs), Schwann cells (SCs), and bone marrow stromal cells (BMSCs). Neurite outgrowth from embryonic dorsal root ganglia (DRG) neurons was used to assess the efficacy of the hydrogels alone or in combination with cultured cells to promote axonal regeneration. The result showed that alginate hydrogel transformed OECs, SCs, and BMSCs into atypical cells with spherical shape and inhibited their metabolic activity. Combination of alginate hydrogel with fibronectin promoted only OECs proliferation. Alginate hydrogel also inhibited outgrowth of DRG neurites, although this effect was attenuated by addition of fibronectin, SCs, or BMSCs. In contrast, matrigel stimulated cell proliferation, preserved the typical morphological features of the cultured cells and induced massive sprouting of DRG neurites. Addition of cultured cells to matrigel did not further improve DRG neurite outgrowth. The present findings suggest that addition of extracellular matrix should be considered when engineering biosynthetic scaffolds on the basis of alginate hydrogels.
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4. |
- Novikova, Liudmila N, et al.
(författare)
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Biodegradable poly-beta-hydroxybutyrate scaffold seeded with Schwann cells to promote spinal cord repair
- 2008
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 29:9, s. 1198-1206
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Tidskriftsartikel (refereegranskat)abstract
- Cavity formation is an important obstacle impeding regeneration after spinal cord injury and bridging strategies are essential to provide physical substrate allowing axons to grow across the lesion site. In this study we evaluated effects of biodegradable tubular conduit made from poly-beta-hydroxybutyrate (PHB) scaffold with predominantly unidirectional fiber orientation and supplemented with cultured adult Schwann cells on axonal regeneration after cervical spinal cord injury in adult rats. After transplantation into the injured spinal cord, plain PHB conduit was well-integrated into posttraumatic cavity and induced modest astroglial reaction. Regenerating axons were found mainly outside the PHB with only single fibers crossing the host-graft interface. No host Schwann cells migrated into the graft. In contrast, when suspension of adult Schwann cells was added to the PHB during transplantation, neurofilament-positive axons filled the conduit and became associated with the implanted cells. Although rubrospinal fibers did not enter the PHB, numerous raphaespinal and CGRP-positive axons were found within the conduit. Modification of PHB surface with fibronectin, laminin or collagen significantly increased Schwann cell attachment and proliferation in vitro. However, transplantation of PHB conduit pre-coated with fibronectin and seeded with Schwann cells did not alter axonal growth response. The results demonstrate that a PHB scaffold promotes attachment, proliferation and survival of adult Schwann cells and supports marked axonal regeneration within the graft.
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5. |
- Welin, Dag, 1978-, et al.
(författare)
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Effects of N-acetyl-cysteine on the survival and regeneration of sural sensory neurons in adult rats
- 2009
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1287:1, s. 58-66
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Tidskriftsartikel (refereegranskat)abstract
- Microsurgical reconstruction of injured peripheral nerves often results in limited functional recovery. One contributing factor is the retrograde neuronal degeneration of sensory neurons in the dorsal root ganglia (DRG) and of motor neurons in the spinal cord. The present study investigates the neuroprotective and growth-promoting effects of N-acetyl-cysteine (NAC) on sensory DRG neurons and spinal motoneurons after sciatic axotomy and nerve grafting in adult rats. Sciatic axotomy and nerve grafting were performed at 1 week after sural DRG neurons and motoneurons were retrogradely labeled with the fluorescent tracer Fast Blue. To assess the efficacy of axonal regeneration, a second fluorescent dye Fluoro-Ruby was applied distal to the graft at 12 weeks after nerve repair. At 8-13 weeks after axotomy, only 52-56% of the sural sensory neurons remained in the lumbar DRG, while the majority of motoneurons survived the sciatic nerve injury. Nerve grafting alone or continuous intrathecal NAC treatment (2.4 mg/day) improved survival of sural DRG neurons. Combined treatment with nerve graft and NAC had significant additive effect on neuronal survival and also increased the number of sensory neurons regenerating across the graft. However, NAC treatment neither affected the number of regenerating motoneurons nor the number of myelinated axons in the nerve graft or in the distal nerve stump. The present results demonstrate that NAC provides a highly significant effect of neuroprotection in an animal nerve injury model and that combination with nerve grafting further attenuates retrograde cell death and promotes regeneration of sensory neurons.
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6. |
- Jivan, Sharmila, et al.
(författare)
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The influence of pre-surgical delay on functional outcome after reconstruction of brachial plexus injuries.
- 2009
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Ingår i: Journal of plastic, reconstructive & aesthetic surgery : JPRAS. - : Elsevier BV. - 1878-0539 .- 1748-6815. ; 62:4, s. 472-479
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Tidskriftsartikel (refereegranskat)abstract
- It has been proposed that delayed surgery after traumatic brachial plexus injury may adversely affect functional outcome. In this study the influence of pre-surgical delay on the outcome of brachial plexus reconstruction was examined retrospectively. All patients who underwent surgery for traumatic brachial plexus injury in the Leeds Plastic and Reconstructive Surgery unit (UK), between 1987 and 2002, were identified. Of the 110 patients identified, 27 had nerve grafting to the upper trunk to restore shoulder and biceps muscle function. Postoperative functional outcome was evaluated in this subgroup of patients. The 27 patients were divided into three groups: surgery <2 weeks (n=10), 2 weeks to 2 months (n=10) and >2 months (n=7) following injury. The efficacy of nerve grafting was correlated to pre- and postoperative biceps strength, which was assessed using the British Medical Research Council (MRC) Motor Grading Scale. In all patients the preoperative elbow grade was M0. The results showed that in the <2 weeks, 2 weeks-2 months and >2 months delay groups, the mean postoperative elbow MRC grades were 4.2+/-SD 1.0, 3.8+/-SD 0.8 and 1.1+/-SD 1.7, respectively. Functionally better results were obtained with early surgery. When surgery was delayed beyond 2 months there was no significant difference between mean pre- and postoperative elbow grades. We therefore believe that early exploration and reconstruction of adult traumatic brachial plexus injuries minimises the pernicious adverse effects of delay attributable to recent findings of the neurobiological effects of axonal damage.
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7. |
- Myslivets, E., et al.
(författare)
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Spatial Equalization of Zero-Dispersion Wavelength Profiles in Nonlinear Fibers
- 2009
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Ingår i: IEEE Photonics Technology Letters. - 1041-1135 .- 1941-0174. ; 21:24, s. 1807-1809
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Tidskriftsartikel (refereegranskat)abstract
- Longitudinal zero-dispersion wavelength (ZDW) fluctuations in long waveguides impose a fundamental limit on the achievable parametric mixer bandwidth. We demonstrate for the first time that the precisely measured ZDW profile can be taken advantage of by applying spatially controlled tension along the fiber length for fluctuation reduction and synthesis of a wide mixer response. The technique was experimentally validated by measuring local dispersion and tension maps and synthesizing a 145-nm-wide fiber parametric amplifier.
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8. |
- Wiberg, Roland, et al.
(författare)
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Heat transfer from a cylinder in axial turbulent flows
- 2005
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Ingår i: International Journal of Heat and Mass Transfer. - : Elsevier BV. - 0017-9310 .- 1879-2189. ; 48:8, s. 1505-1517
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Tidskriftsartikel (refereegranskat)abstract
- Local convective heat transfer coefficients were measured on a two-diameter long cylinder in axial flows of air at conditions unexplored so far, by using thermochromic liquid crystals (TLC) coated on an electrically heated strip-foil consisting bonded to the external surfaces. The Reynolds numbers (Re) based on the cylinder diameter were between 8.9 x 10(4) and 6.17 x 10(5), and the flow in front of the cylinder was modified in some cases by the use of a turbulence generating grid, or by circular disc inserts of two sizes placed upstream of the cylinder. These created a major change in the local convective heat transfer coefficient distribution on the cylinder. Increase of the turbulence intensity from Tu < 0.1% to Tu = 6.7% at the same Re increased the average calculated Nusselt number Nu over the cylinder by 25%, and decreased the Nu non-uniformity over the surface. One of the flow modification inserts also reduced significantly the Nu non-uniformity. The position of flow reattachment was measured using tufts. Our heat transfer data agree well with the small amount if data published of others, when extrapolated to their conditions. Correlations between the Nu and Re in the form Nu = CRee were established and presented for the average Nu on the front, middle and rear cylinder surfaces, and the variation of the local exponent e was shown along the cylinder. Introducing a new technique, a TLC-coated heated flat plate mounted in the flow above the cylinder in the meridional plane was demonstrated to help visualize the flow field above the cylinder. A track of maximum convective coefficients on this plate was found similar in position to the stream line dividing the forward and backward flows in a case measured for the separated flow in a past study.
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