Neuroglial differentiation of adult enteric neuronal progenitor cells as a function of extracellular matrix composition.
Neuroglial differentiation of adult enteric neuronal progenitor cells as a function of extracellular matrix composition.
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DOI：
10.1016/j.biomaterials.2013.05.023
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发表时间：
2013-09
期刊：
影响因子：
14
通讯作者：
Bitar, Khalil N.
中科院分区：
文献类型：
--
作者：
Raghavan, Shreya;Gilmont, Robert R.;Bitar, Khalil N.
肠神经元祖细胞是可以从胎儿、出生后和成人肠道分离的神经嵴来源的干细胞。神经干细胞移植是一种新兴的治疗模式，以取代功能障碍或失去肠神经元在几个无神经节疾病的胃肠道。确定肠神经元祖细胞的适当微环境的动力来自于植入后改善存活率和表型稳定性的需要。细胞外基质成分可以调节干细胞命运和直接分化。体内成年哺乳动物肌间神经节被主要由IV型胶原蛋白、层粘连蛋白和硫酸乙酰肝素蛋白聚糖组成的基质包围。在这些研究中，当在神经ECM基质的各种组合上培养时，诱导从全层兔肠分离的成年哺乳动物肠神经元祖细胞分化。神经元和神经胶质分化作为ECM组合物的函数在涂覆的玻璃盖玻片上进行了研究。多聚赖氨酸包被的盖玻片（对照）支持广泛的神经胶质分化，但支持非常小的神经元分化。单个培养基质（层粘连蛋白、胶原蛋白I和胶原蛋白IV）有利于神经元和胶质细胞的分化。层粘连蛋白或硫酸乙酰肝素的胶原基质的加入改善神经元分化，显着增加神经突的长度，分支和神经元网络的形成开始。神经胶质分化是广泛的控制多聚赖氨酸包被的盖玻片。添加层粘连蛋白或硫酸乙酰肝素的复合胶原基质显着降低神经胶质细胞的免疫荧光。单独和组合评价各种神经ECM组分以研究其对成体肠神经元祖细胞的神经胶质分化的影响。我们的研究结果表明，特定的ECM底物，包括IV型胶原蛋白，层粘连蛋白和硫酸乙酰肝素支持和维持神经元和神经胶质细胞分化到不同程度。在这里，我们确定了一种基质组合物优化组织工程可移植神经支配的胃肠道平滑肌结构，以补救无神经节疾病。
Enteric neuronal progenitor cells are neural crest-derived stem cells that can be isolated from fetal, post-natal and adult gut. Neural stem cell transplantation is an emerging therapeutic paradigm to replace dysfunctional or lost enteric neurons in several aganglionic disorders of the GI tract. The impetus to identify an appropriate microenvironment for enteric neuronal progenitor cells derives from the need to improve survival and phenotypic stability following implantation. Extracellular matrix composition can modulate stem cell fate and direct differentiation. Adult mammalian myenteric ganglia in vivo are surrounded by a matrix composed primarily of Collagen IV, Laminin and a Heparan sulfate proteoglycan. In these studies, adult mammalian enteric neuronal progenitor cells isolated from full thickness rabbit intestines were induced to differentiate when cultured on various combinations of neural ECM substrates. Neuronal and glial differentiation was studied as a function of ECM composition on coated glass coverslips. Poly- lysine coated coverslips (control) supported extensive glial differentiation but very minimal neuronal differentiation. Individual culture substrata (Laminin, Collagen I and Collagen IV) were conducive for both neuronal and glial differentiation. The addition of laminin or heparan sulfate to collagen substrates improved neuronal differentiation, significantly increased neurite lengths, branching and initiation of neuronal network formation. Glial differentiation was extensive on control poly lysine coated coverslips. Addition of laminin or heparan sulfate to composite collagen substrates significantly reduced glial immunofluorescence. Various neural ECM components were evaluated individually and in combination to study their effect of neuroglial differentiation of adult enteric neuronal progenitor cells. Our results indicate that specific ECM substrates that include type IV Collagen, laminin and heparan sulfate support and maintain neuronal and glial differentiation to different extents. Here, we identify a matrix composition optimized to tissue engineer transplantable innervated GI smooth muscle constructs to remedy aganglionic disorders.
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