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Differentiation of Bone Marrow Stem Cells into Schwann Cells for the Promotion of Neurite Outgrowth on Electrospun Fibers.

ABSTRACT: Seeding nerve guidance conduits with Schwann cells can improve the outcome of peripheral nerve injury repair. Bone marrow stem cells (BMSCs) represent a good choice of cell source as they can differentiate into Schwann cells under appropriate conditions. In this work, we systematically investigated the differentiation of BMSCs into Schwann cells on scaffolds comprising electrospun fibers. We changed the alignment, diameter, and surface properties of the fibers to optimize the differentiation efficiency. The uniaxial alignment of fibers not only promoted the differentiation of BMSCs into Schwann cells but also dictated the morphology and alignment of the derived cells. Coating the surface of aligned fibers with laminin further enhanced the differentiation and thus increased the secretion of neurotrophins. When co-cultured with PC12 cells or chick dorsal root ganglion, the as-derived Schwann cells were able to promote the outgrowth of neurites from cell bodies and direct their extension along the fibers, demonstrating the positive impacts of both the neurotrophic effect and the morphological contact guidance. This work offers a promising strategy for integrating fiber guidance with stem cell therapy to augment peripheral nerve injury repair.

SUBMITTER: Xue J

PROVIDER: S-EPMC5489349 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Differentiation of Bone Marrow Stem Cells into Schwann Cells for the Promotion of Neurite Outgrowth on Electrospun Fibers.

Xue Jiajia J Yang Junyu J O'Connor Deirdre M DM Zhu Chunlei C Huo Da D Boulis Nicholas M NM Xia Younan Y

ACS applied materials & interfaces 20170330 14

Seeding nerve guidance conduits with Schwann cells can improve the outcome of peripheral nerve injury repair. Bone marrow stem cells (BMSCs) represent a good choice of cell source as they can differentiate into Schwann cells under appropriate conditions. In this work, we systematically investigated the differentiation of BMSCs into Schwann cells on scaffolds comprising electrospun fibers. We changed the alignment, diameter, and surface properties of the fibers to optimize the differentiation eff ...[more]

PMID: 28322042

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Project description:Endogenous electric fields are instructive during embryogenesis by acting to direct cell migration, and postnatally, they can promote axonal growth after injury (McCaig 1991, Al-Majed 2000). However, the mechanisms for these changes are not well understood. Application of an appropriate electrical stimulus may increase the rate and success of nerve repair by directly promoting axonal growth. Previously, DC electrical stimulation at 50?mV/mm (1 mA, 8?h duration) was shown to promote neurite outgrowth and a more pronounced effect was observed if both peripheral glia (Schwann cells) and neurons were co-stimulated. If electrical stimulation is delivered to an injury site, both the neurons and all resident non-neuronal cells [e.g., Schwann cells, endothelial cells, fibroblasts] will be treated and this biophysical stimuli can influence axonal growth directly or indirectly via changes to the resident, non-neuronal cells. In this work, non-neuronal cells were electrically stimulated, and changes in morphology and neuro-supportive cells were evaluated. Schwann cell response (morphology and orientation) was examined after an 8?h stimulation over a range of DC fields (0-200?mV/mm, DC 1 mA), and changes in orientation were observed. Electrically prestimulating Schwann cells (50?mV/mm) promoted 30% more neurite outgrowth relative to co-stimulating both Schwann cells with neurons, suggesting that electrical stimulation modifies Schwann cell phenotype. Conditioned medium from the electrically prestimulated Schwann cells promoted a 20% increase in total neurite outgrowth and was sustained for 72?h poststimulation. An 11-fold increase in nerve growth factor but not brain-derived neurotrophic factor or glial-derived growth factor was found in the electrically prestimulated Schwann cell-conditioned medium. No significant changes in fibroblast or endothelial morphology and neuro-supportive behavior were observed poststimulation. Electrical stimulation is widely used in clinical settings; however, the rational application of this cue may directly impact and enhance neuro-supportive behavior, improving nerve repair.

Project description:Aligned, electrospun fiber scaffolds provide topographical guidance for regenerating neurons and glia after central nervous system injury. To date, no study has explored how fiber surface nanotopography affects astrocyte response to fibrous scaffolds. Astrocytes play important roles in the glial scar, the blood brain barrier, and in maintaining homeostasis in the central nervous system. In this study, electrospun poly L-lactic acid fibers were engineered with smooth, pitted, or divoted surface nanotopography. Cortical or spinal cord primary rat astrocytes were cultured on the surfaces for either 1 or 3 d to examine the astrocyte response over time. The results showed that cortical astrocytes were significantly shorter and broader on the pitted and divoted fibers compared to those on smooth fibers. However, spinal cord astrocyte morphology was not significantly altered by the surface features. These findings indicate that astrocytes from unique anatomical locations respond differently to the presence of nanotopography. Western blot results show that the differences in morphology were not associated with significant changes in glial fibrillary acidicprotein (GFAP) or vinculin in either astrocyte population, suggesting that surface pits and divots do not induce a reactive phenotype in either cortical or spinal cord astrocytes. Finally, astrocytes were co-cultured with dorsal root ganglia to determine how the surfaces affected astrocyte-mediated neurite outgrowth. Astrocytes cultured on the fibers for shorter periods of time (1 d) generally supported longer neurite outgrowth. Pitted and divoted fibers restricted spinal cord astrocyte-mediated neurite outgrowth, while smooth fibers increased 3 d spinal cord astrocyte-mediated neurite outgrowth. In total, fiber surface nanotopography can influence astrocyte elongation and influence the capability of astrocytes to direct neurites. Therefore, fiber surface characteristics should be carefully controlled to optimize astrocyte-mediated axonal regeneration.

Dataset Information

Differentiation of Bone Marrow Stem Cells into Schwann Cells for the Promotion of Neurite Outgrowth on Electrospun Fibers.

Publications

Differentiation of Bone Marrow Stem Cells into Schwann Cells for the Promotion of Neurite Outgrowth on Electrospun Fibers.

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