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Influence of alginate cross-linking method on neurite response to microencapsulated neurotrophin-producing fibroblasts

机译:海藻酸盐交联方法对神经突对微囊化产生神经营养蛋白的成纤维细胞反应的影响

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摘要

Transplantation of cells genetically modified to produce neurotrophins is a promising spinal cord repair strategy. Previously we showed that fibroblasts engineered to produce brain-derived neurotrophic factor (Fb/BDNF) microencapsulated in alginate survive, continue to grow and express bioactive BDNF. We here compared the effects of different alginate crosslinkers on dorsal root ganglia (DRG) neurite growth using alginate-encapsulated Fb/BDNF. Aqueous sodium alginate (±Fb/BDNF) was contacted with different calcium salts, and used as substrate for DRG growth. Length, number and orientation of neurites were measured. Chloride or carbonate salts promoted significantly more neurite growth than sulphate, with or without Fb/BDNF, although encapsulated Fb/BDNF stimulated significantly more neurite growth than cell-free. An Fb/BDNF-derived neurotrophin concentration gradient directionally guided DRG neurite growth. This positive effect of alginate-encapsulated Fb/BDNF on neurite growth/guidance shows promise for enhanced regeneration and guidance of axons towards a specific target in the injured spinal cord.
机译:基因改造产生神经营养蛋白的细胞的移植是一种有希望的脊髓修复策略。以前,我们表明,设计成能产生微囊化在藻酸盐中的脑源性神经营养因子(Fb / BDNF)的成纤维细胞能够生存,继续生长并表达具有生物活性的BDNF。我们在这里比较了不同藻酸盐交联剂对藻酸盐包封的Fb / BDNF对背根神经节(DRG)神经突生长的影响。海藻酸钠水溶液(±Fb / BDNF)与不同的钙盐接触,并用作DRG生长的底物。测量了神经突的长度,数量和取向。尽管有或没有Fb / BDNF,氯化物或碳酸盐比无硫酸盐促进的神经突生长明显多于硫酸盐,尽管封装的Fb / BDNF比无细胞刺激的神经突生长明显多。 Fb / BDNF衍生的神经营养蛋白浓度梯度可指导DRG神经突的生长。藻酸盐包封的Fb / BDNF对神经突生长/引导的这种积极作用表明有望增强再生和将轴突导向受损脊髓中的特定靶标。

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