Oligodendrocyte Precursor Cell Viability, Proliferation, and Morphology is Dependent on Mesh Size and Storage Modulus in 3D Poly(ethylene glycol)-Based Hydrogels.
Oligodendrocyte Precursor Cell Viability, Proliferation, and Morphology is Dependent on Mesh Size and Storage Modulus in 3D Poly(ethylene glycol)-Based Hydrogels.
复制标题
少突胶质细胞前体细胞的活力、增殖和形态取决于 3D 聚乙二醇水凝胶的网格尺寸和储能模量。
DOI：
10.1021/acsbiomaterials.7b00374
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发表时间：
2017
影响因子：
5.8
通讯作者：
K. Lampe
中科院分区：
文献类型：
--
作者：
Lauren N. Russell;K. Lampe
中枢神经系统(CNS)中的少突胶质细胞负责产生髓鞘，髓鞘是神经元轴突周围的一层电绝缘层。当髓鞘受损时，神经元无法维持正常的沟通，这可能在患者身上表现为疼痛、活动能力和视力丧失。已有大量研究使用生物材料来促进神经元再生，但尽管髓鞘受损具有广泛的意义，但生物材料环境如何影响少突胶质前体细胞(OPC)的增殖或分化为髓鞘少突胶质细胞，人们知之甚少。这项工作研究了聚乙二醇基水凝胶的储存模数和网目尺寸如何通过两种不同的机制改变，直接影响两种被包裹并在3D中培养的OPC细胞的增殖。两种OPC细胞的存活和增殖依赖于水凝胶的肿胀和硬度，在顺应性较强的凝胶中，ATP浓度增加得更多。OPC在3D水凝胶中倍增，在交联度较低的条件下产生明显更大的球体。更硬、更高交联度的材料会导致OPC受体PDGFRα的表达增加，这表明在顺应性材料中，致力于少突胶质细胞谱系或去分化的细胞较少。在3D基质中掺入层粘连蛋白对细胞的活性或增殖几乎没有影响。这些发现提供了关于网眼大小和硬度如何影响OPC的有价值的信息，在这些情况下，顺应性更好的材料有利于OPC的增殖，而对成熟的少突胶质细胞谱系的承诺较少。这些信息将有助于翻译生物材料的开发，以刺激少突胶质细胞成熟以促进神经再生。
Oligodendrocytes in the central nervous system (CNS) are responsible for generating myelin, an electrically insulating layer around neuronal axons. When myelin is damaged, neurons are incapable of sustaining normal communications, which can manifest in patients as pain and loss of mobility and vision. A plethora of research has used biomaterials to promote neuronal regeneration, but despite the wide implications of a disrupted myelin sheath, very little is known about how biomaterial environments impact proliferation of oligodendrocyte precursor cells (OPCs) or their differentiation into myelinating oligodendrocytes. This work investigates how the storage modulus and mesh size of a polyethylene glycol (PEG)-based hydrogel, varied via two different mechanisms, directly affect the proliferation of two OPC lines encapsulated and cultured in 3D. Viability and proliferation of both OPC lines was dependent on hydrogel swelling and stiffness, where the concentration of ATP increased more in the more compliant gels. OPCs multiplied in the 3D hydrogels, creating significantly larger spheroids in the less cross-linked conditions. Stiffer, more highly cross-linked materials lead to greater expression of PDGFRα, an OPC receptor, indicating that fewer cells were committed to the oligodendrocyte lineage or had dedifferentiated in compliant materials. Laminin incorporation in the 3D matrix was found to have little effect on viability or proliferation. These findings provide valuable information on how mesh size and stiffness affect OPCs where more compliant materials favor proliferation of OPCs with less commitment to a mature oligodendrocyte lineage. Such information will be useful in the development of translational biomaterials to stimulate oligodendrocyte maturation for neural regeneration.