Engineered neural tissue

  • 文章类型: Journal Article
    Tissue engineering approaches in nerve regeneration often aim to improve results by bridging nerve defects with conduits that mimic key features of the nerve autograft. One such approach uses Schwann cell self-alignment and stabilization within collagen gels to generate engineered neural tissue (EngNT). In this study, we investigated whether a novel blend of fibrin and collagen could be used to form EngNT, as before EngNT design a beneficial effect of fibrin on Schwann cell proliferation was observed. A range of blend formulations was tested in terms of mechanical behavior (gel formation, stabilization, swelling, tensile strength, and stiffness), and lead formulations were assessed in vitro. A 90% collagen 10% fibrin blend was found to promote SCL4.1/F7 Schwann cell viability and supported the formation of aligned EngNT, which enhanced neurite outgrowth in vitro (NG108 cells) compared to formulations with higher and lower fibrin content. Initial in vivo tests in an 8 mm rat sciatic nerve model using rolled collagen-fibrin EngNT rods revealed a significantly enhanced axonal count in the midsection of the repair, as well as in the distal part of the nerve after 4 weeks. This optimized collagen-fibrin blend therefore provides a novel way to improve the capacity of EngNT to promote regeneration following peripheral nerve injury.
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  • 文章类型: Journal Article
    背景:颅内压(ICP)升高伴随着许多神经系统急症,并且缺乏确定细胞病理生理学的模型。这限制了我们识别与从生理到病理ICP的病理进展相关的细胞和分子生物标志物的能力。
    我们开发了一种压力诱发脑损伤的离体模型,它结合了3D神经细胞培养和新开发的压力控制细胞培养培养箱(PC3I)。维持在3D肽缀合的藻酸盐水凝胶中的人星形胶质细胞和神经元经受模拟ICP的生理和病理水平的压力长达48小时,以评估分离压力对细胞活力的最早影响并量化压力诱导的细胞损伤的早期指标。
    结果:与在生理压力下生长的对照细胞培养物相比,持续的病理压力暴露以细胞特异性方式增加了细胞内ATP的释放.18小时的持续压力导致从神经元而不是星形胶质细胞释放的ATP增加。
    细胞培养培养箱在正常大气压下维持培养。基于多个文献检索,我们不知道任何其他细胞培养箱系统可以改变维持原代CNS细胞的压力。
    结论:该模型模拟了脑积水患者颅内压升高的临床特征,并提供了在新生儿脑积水最早进展期间遇到的病理信号的第一个估计。该模型应提供更好地理解与升高的ICP的最早阶段相关的病理生物标志物的手段。
    BACKGROUND: Elevated intracranial pressure (ICP) accompanying a number of neurological emergencies is poorly understood, and lacks a model to determine cellular pathophysiology. This limits our ability to identify cellular and molecular biomarkers associated with the pathological progression from physiologic to pathologic ICP.
    UNASSIGNED: We developed an ex vivo model of pressure-induced brain injury, which combines 3D neural cell cultures and a newly developed Pressure Controlled Cell Culture Incubator (PC3I). Human astrocytes and neurons maintained in 3D peptide-conjugated alginate hydrogels were subjected to pressures that mimic both physiologic and pathologic levels of ICP for up to 48h to evaluate the earliest impacts of isolated pressure on cellular viability and quantify early indicators of pressure-induced cellular injury.
    RESULTS: Compared to control cell cultures grown under physiologic pressure, sustained pathologic pressure exposure increased the release of intracellular ATP in a cell-specific manner. Eighteen hours of sustained pressure resulted in increased ATP release from neurons but not astrocytes.
    UNASSIGNED: Cell culture incubators maintain cultures at normal atmospheric pressure. Based on multiple literature searches, we are not aware of any other cell culture incubator systems that modify the pressure at which primary CNS cells are maintained.
    CONCLUSIONS: This model simulates the clinical features of elevated ICP encountered in patients with hydrocephalus, and provides a first estimate of the pathological signaling encountered during the earliest perid of progression in neonatal hydrocephalus. This model should provide a means to better understand the pathological biomarkers associated with the earliest stages of elevated ICP.
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  • 文章类型: Journal Article
    Traumatic nerve injuries are common conditions treated by hand surgeons, and the optimal treatment of a severed nerve requires providing a healthy wound bed, generous trimming to healthy nerve substance, and a minimal-tension approximation. The gold standard for repair of a critical nerve gap has been the nerve autograft. However, results are generally less favorable than direct suture. Autogenous and synthetic conduits and processed nerve allografts have been developed as less morbid and more convenient alternatives to autografts, but the reported outcomes have been uneven. Engineered neural tissues show great promise in inducing nerve regeneration across a gap.
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  • 文章类型: Journal Article
    人类多能干细胞(hPSC)代表了现代医学中一个令人兴奋的新领域,现在是许多研究人员和媒体关注的焦点。由于干细胞可能有助于疾病建模,药物筛选,甚至是治疗方法。在这次审查中,我们首先关注这些细胞的神经分化。在第二部分中,我们比较了可用的各种细胞类型及其在体外建模中的优势。然后,我们提供了有关两个主要生物医学应用的“最新”报告:(1)药物和毒性筛选以及(2)神经组织替代。最后,我们概述了目前使用分化hPSCs的生物医学研究。
    Human pluripotent stem cells (hPSCs) represent a new and exciting field in modern medicine, now the focus of many researchers and media outlets. The hype is well-earned because of the potential of stem cells to contribute to disease modeling, drug screening, and even therapeutic approaches. In this review, we focus first on neural differentiation of these cells. In a second part we compare the various cell types available and their advantages for in vitro modeling. Then we provide a \"state-of-the-art\" report about two major biomedical applications: (1) the drug and toxicity screening and (2) the neural tissue replacement. Finally, we made an overview about current biomedical research using differentiated hPSCs.
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