| 1. |
- Alakpa, Enateri V., et al.
(författare)
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The Prismatic Topography of Pinctada maxima Shell Retains Stem Cell Multipotency and Plasticity In Vitro
- 2018
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Ingår i: Advanced Biosystems. - : WILEY-V C H VERLAG GMBH. - 2366-7478. ; 2:6
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Tidskriftsartikel (refereegranskat)abstract
- The shell of the bivalve mollusc Pinctada maxima is composed of the calcium carbonate polymorphs calcite and aragonite (nacre). Mother-of-pearl, or nacre, induces vertebrate cells to undergo osteogenesis and has good osteointegrative qualities in vivo. The calcite counterpart, however, is less researched in terms of the response of vertebrate cells. This study shows that isolation of calcite surface topography from the inherent chemistry allows viable long-term culture of bone marrow derived mesenchymal stem cells (MSCs). Self-renewal is evident from the increased gene expression of the self-renewal markers CD63, CD166, and CD271 indicating that cells cultured on the calcite topography maintain their stem cell phenotype. MSCs also retain their multipotency and can undergo successful differentiation into osteoblasts and adipocytes. When directed to adipogenesis, MSCs cultured on prism replicas are more amenable to differentiation than MSCs cultured on tissue culture polystyrene indicating a higher degree of plasticity in MSCs growing on calcite P. maxima prismatic topography. The study highlights the potential of the calcite topography of P. maxima as a biomimetic design for supporting expansion of MSC populations in vitro, which is of fundamental importance if it meets the demands for autologous MSCs for therapeutic use.
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| 2. |
- Thomson, Suzanne E., et al.
(författare)
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Bioengineered nerve conduits and wraps for peripheral nerve repair of the upper limb
- 2017
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Ingår i: Cochrane Database of Systematic Reviews. - 1361-6137. ; 2017:3
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Forskningsöversikt (refereegranskat)abstract
- This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess and compare the effects and complication rates of licensed bioengineered nerve conduits or wraps for surgical repair of traumatic peripheral nerve injuries of the upper limb. To compare effects and complications against the current gold surgical standard (nerve autograft).
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| 3. |
- Thomson, Suzanne E., et al.
(författare)
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Bioengineered nerve conduits and wraps for peripheral nerve repair of the upper limb
- 2022
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Ingår i: Cochrane Database of Systematic Reviews. - : John Wiley & Sons. - 1469-493X .- 1469-493X. ; 2022:12
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Forskningsöversikt (refereegranskat)abstract
- This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess and compare the effects and complication rates of licensed bioengineered nerve conduits or wraps for surgical repair of traumatic peripheral nerve injuries of the upper limb. To compare effects and complications against the current gold surgical standard (nerve autograft).
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| 4. |
- Thomson, Suzanne E., et al.
(författare)
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Microtopographical cues promote peripheral nerve regeneration via transient mTORC2 activation
- 2017
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Ingår i: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 60, s. 220-231
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Tidskriftsartikel (refereegranskat)abstract
- Despite microsurgical repair, recovery of function following peripheral nerve injury is slow and often incomplete. Outcomes could be improved by an increased understanding of the molecular biology of regeneration and by translation of experimental bioengineering strategies. Topographical cues have been shown to be powerful regulators of the rate and directionality of neurite regeneration, and in this study we investigated the downstream molecular effects of linear micropatterned structures in an organotypic explant model. Linear topographical cues enhanced neurite outgrowth and our results demonstrated that the mTOR pathway is important in regulating these responses. mTOR gene expression peaked between 48 and 72 h, coincident with the onset of rapid neurite outgrowth and glial migration, and correlated with neurite length at 48 h. mTOR protein was located to glia and in a punctate distribution along neurites. mTOR levels peaked at 72 h and were significantly increased by patterned topography (p < 0.05). Furthermore, the topographical cues could override pharmacological inhibition. Downstream phosphorylation assays and inhibition of mTORC1 using rapamycin highlighted mTORC2 as an important mediator, and more specific therapeutic target. Quantitative immunohistochemistry confirmed the presence of the mTORC2 component rictor at the regenerating front where it co-localised with F-actin and vinculin. Collectively, these results provide a deeper understanding of the mechanism of action of topography on neural regeneration, and support the incorporation of topographical patterning in combination with pharmacological mTORC2 potentiation within biomaterial constructs used to repair peripheral nerves.Statement of Significance: Peripheral nerve injury is common and functionally devastating. Despite microsurgical repair, healing is slow and incomplete, with lasting functional deficit. There is a clear need to translate bioengineering approaches and increase our knowledge of the molecular processes controlling nerve regeneration to improve the rate and success of healing. Topographical cues are powerful determinants of neurite outgrowth and represent a highly translatable engineering strategy. Here we demonstrate, for the first time, that microtopography potentiates neurite outgrowth via the mTOR pathway, with the mTORC2 subtype being of particular importance. These results give further evidence for the incorporation of microtopographical cues into peripheral nerve regeneration conduits and indicate that mTORC2 may be a suitable therapeutic target to potentiate nerve regeneration.
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