Insights Into the Role and Potential of Schwann Cells for Peripheral Nerve Repair From Studies of Development and Injury.
Insights Into the Role and Potential of Schwann Cells for Peripheral Nerve Repair From Studies of Development and Injury.
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DOI：
10.3389/fnmol.2020.608442
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发表时间：
2020
影响因子：
4.8
通讯作者：
Schuurmans C
中科院分区：
文献类型：
--
作者：
Balakrishnan A;Belfiore L;Chu TH;Fleming T;Midha R;Biernaskie J;Schuurmans C
由创伤或疾病引起的外周神经损伤可导致感觉和运动缺陷以及神经性疼痛。尽管声称周围神经有自我修复的能力，但终身残疾是常见的。新的分子和细胞见解已经开始揭示为什么外周神经的修复能力有限。周围神经主要由轴突和许旺细胞组成，许旺细胞是产生髓鞘以促进电脉冲快速传导的支持神经胶质细胞。雪旺氏细胞是成功的神经再生所必需的;它们对损伤做出部分“去分化”反应，重新启动支持神经修复的发育基因的表达。然而，慢性神经损伤、疾病和衰老中发生的许旺细胞功能障碍限制了它们支持内源性修复的能力，从而使患者预后恶化。使用外源性许旺细胞的基于细胞增殖的治疗方法可能是治愈性的，但并非所有许旺细胞都具有“修复”表型，其定义为促进轴突生长、维持增殖表型和使轴突髓鞘再生的能力。两种细胞替代策略正在倡导用于外周神经修复：前瞻性分离用于自体细胞移植的“修复”施旺细胞，这受到供应挑战的阻碍，以及多能干细胞的定向分化或可接近的体细胞向诱导的施旺细胞的谱系转化，具有“无限”供应的潜力。所有的方法都需要一个坚实的理解的分子机制指导雪旺细胞的发展和修复表型，我们在这里审查。这些研究为目前设计基于神经胶质细胞的外周神经再生疗法提供了必要的背景。
Peripheral nerve injuries arising from trauma or disease can lead to sensory and motor deficits and neuropathic pain. Despite the purported ability of the peripheral nerve to self-repair, lifelong disability is common. New molecular and cellular insights have begun to reveal why the peripheral nerve has limited repair capacity. The peripheral nerve is primarily comprised of axons and Schwann cells, the supporting glial cells that produce myelin to facilitate the rapid conduction of electrical impulses. Schwann cells are required for successful nerve regeneration; they partially “de-differentiate” in response to injury, re-initiating the expression of developmental genes that support nerve repair. However, Schwann cell dysfunction, which occurs in chronic nerve injury, disease, and aging, limits their capacity to support endogenous repair, worsening patient outcomes. Cell replacement-based therapeutic approaches using exogenous Schwann cells could be curative, but not all Schwann cells have a “repair” phenotype, defined as the ability to promote axonal growth, maintain a proliferative phenotype, and remyelinate axons. Two cell replacement strategies are being championed for peripheral nerve repair: prospective isolation of “repair” Schwann cells for autologous cell transplants, which is hampered by supply challenges, and directed differentiation of pluripotent stem cells or lineage conversion of accessible somatic cells to induced Schwann cells, with the potential of “unlimited” supply. All approaches require a solid understanding of the molecular mechanisms guiding Schwann cell development and the repair phenotype, which we review herein. Together these studies provide essential context for current efforts to design glial cell-based therapies for peripheral nerve regeneration.
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影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
DOI：
10.1073/pnas.111092198
发表时间：
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