Novel Acellular Scaffold Made from Decellularized Schwann Cell Sheets for Peripheral Nerve Regeneration.

Novel Acellular Scaffold Made from Decellularized Schwann Cell Sheets for Peripheral Nerve Regeneration.
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DOI:
10.1007/s40883-015-0003-2
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发表时间:
2015-12
影响因子:
2.6
通讯作者:
Yu X
Yu X
中科院分区:
其他
文献类型:
--
作者:
Junka R;Yu X

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雪旺细胞和神经元周围的细胞外基质提供了发育过程中细胞表型的关键决定因素以及刺激和引导再生的重要线索。利用细胞片层技术,我们开发了一种富含雪旺细胞天然细胞外基质的新型支架。雪旺细胞生长成片状并分层到聚己内酯纤维上作为支撑。这些构建体脱细胞后,细胞外基质中残留有少量核酸。这种细胞外基质沉积方法在脱细胞后比传统接种方法提供了更多的蛋白质。此外,分离的基质比共价结合的层粘连蛋白更好地支持雪旺细胞的增殖。在脱细胞片上生长的雪旺细胞的增殖和分化通过 Erbb2 和髓鞘蛋白零的上调来补充。 β1 和 γ1 链的层粘连蛋白表达也升高。在脱细胞片上生长的 PC12 细胞比单独排列的聚己内酯纤维产生更长的神经突延伸,证明了这些支架在未来周围神经再生研究中使用的潜力。周围神经损伤提出了严重的临床需求,大约 50% 的手术病例只能实现部分功能恢复。为了更好地引导神经再生,神经组织的支持细胞被生长成片状,随后脱细胞,留下无数周围的蛋白质作为支架。结构已被证明可以在体外支持细胞生长和神经突延伸。未来的项目将结合神经组织中存在的各种细胞类型以及干细胞,以完全支持和重建周围神经的结构。
Extracellular matrix surrounding Schwann cells and neurons provides critical determinants of cellular phenotype during development as well as essential cues in stimulating and guiding regrowth. Using cell sheet technology, we developed a novel scaffold enriched with native extracellular matrix from Schwann cells. Schwann cells were grown into sheets and layered onto polycaprolactone fibers for support. Upon decellularization of these constructs, extracellular matrix remained with few traces of nucleic acids. This method of deposition of extracellular matrix provided more protein than traditional seeding method after decellularization. Additionally, the isolated matrix supported proliferation of Schwann cells better than covalently bound laminin. The proliferation and differentiation of Schwann cells grown on decellularized sheets were complemented by upregulation of Erbb2 and myelin protein zero. Laminin expression of β1 and γ1 chains was also elevated. PC12 cells grown on decellularized sheets produced longer neurite extensions than aligned polycaprolactone fibers alone, proving potential of these scaffolds to be used in future peripheral nerve regenerative studies. Peripheral nerve injuries present a serious clinical need with approximately 50 % of surgical cases achieving only some restoration of function. In order to better guide regenerating nerves, supporting cells of the nerve tissue were grown into sheets and subsequently decellularized, leaving a myriad of surrounding protein as a scaffold. Constructs have been shown to support cell growth and neurite extension in vitro. Future projects will combine various cell types present in the nerve tissue as well as stem cells to fully support and reconstruct architecture of the peripheral nerves.