Guiding Oligodendrocyte Precursor Cell Maturation With Urokinase Plasminogen Activator-Degradable Elastin-like Protein Hydrogels
Guiding Oligodendrocyte Precursor Cell Maturation With Urokinase Plasminogen Activator-Degradable Elastin-like Protein Hydrogels
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DOI：
10.1021/acs.biomac.0c00828
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发表时间：
2020-12-01
影响因子：
6.2
通讯作者：
Lampe, Kyle J.
中科院分区：
文献类型：
--
作者：
Meco, Edi;Zheng, W. Sharon;Lampe, Kyle J.
脱髓鞘损伤和疾病，如多发性硬化症，影响着全世界数百万人。少突胶质细胞前体细胞 (OPC) 具有修复脱髓鞘组织的潜力，因为它们既可以自我更新，又可以分化为少突胶质细胞 (OL)，即中枢神经系统 (CNS) 的髓鞘生成细胞。细胞-基质相互作用影响 OPC 分化为 OL，但该过程尚未完全了解。生物材料水凝胶系统有助于阐明细胞-基质相互作用，因为它们可以在体外环境中模拟天然中枢神经系统组织的特定特性。我们研究了 OPC 成熟为 OL 是否受到与尿激酶纤溶酶原激活剂 (uPA) 可降解细胞外基质 (ECM) 相互作用的影响。 uPA 是一种蛋白水解酶，在发育中的大鼠大脑中短暂上调，uPA 表达峰值与体内髓磷脂生成的增加相关。通过双标记马赛克分析技术 (MADM OPC) 分离的 OPC 样细胞在培养物中产生低分子量 uPA。 MADM OPC 被封装在两种相似的弹性蛋白样蛋白 (ELP) 水凝胶系统中：一种是 uPA 可降解的，另一种是不可降解的。封装的 MADM OPC 在 uPA 可降解和不可降解的 ELP 水凝胶中具有相似的活力、增殖和代谢活性。然而，OPC 成熟相关基因的表达表明，uPA 可降解 ELP 水凝胶促进了 MADM OPC 成熟，尽管不足以使这些细胞分化为 OL。
Demyelinating injuries and diseases, like multiple sclerosis, affect millions of people worldwide. Oligodendrocyte precursor cells (OPCs) have the potential to repair demyelinated tissues because they can both self-renew and differentiate into oligodendrocytes (OLs), the myelin producing cells of the central nervous system (CNS). Cell-matrix interactions impact OPC differentiation into OLs, but the process is not fully understood. Biomaterial hydrogel systems help to elucidate cell-matrix interactions because they can mimic specific properties of native CNS tissues in an in vitro setting. We investigated whether OPC maturation into OLs is influenced by interacting with a urokinase plasminogen activator (uPA) degradable extracellular matrix (ECM). uPA is a proteolytic enzyme that is transiently upregulated in the developing rat brain, with peak uPA expression correlating with an increase in myelin production in vivo. OPC-like cells isolated through the Mosaic Analysis with Double Marker technique (MADM OPCs) produced low-molecular-weight uPA in culture. MADM OPCs were encapsulated into two otherwise similar elastin-like protein (ELP) hydrogel systems: one that was uPA degradable and one that was nondegradable. Encapsulated MADM OPCs had similar viability, proliferation, and metabolic activity in uPA degradable and nondegradable ELP hydrogels. Expression of OPC maturation-associated genes, however, indicated that uPA degradable ELP hydrogels promoted MADM OPC maturation although not sufficiently for these cells to differentiate into OLs.