Delivering Mesenchymal Stem Cells in Collagen Microsphere Carriers to Rabbit Degenerative Disc: Reduced Risk of Osteophyte Formation
Delivering Mesenchymal Stem Cells in Collagen Microsphere Carriers to Rabbit Degenerative Disc: Reduced Risk of Osteophyte Formation
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DOI：
10.1089/ten.tea.2013.0498
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发表时间：
2014-05-01
影响因子：
4.1
通讯作者：
Chan, Barbara Pui
中科院分区：
文献类型：
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作者：
Li, Yuk Yin;Diao, Hua Jia;Chan, Barbara Pui
间充质干细胞(MSCs)具有治疗早期椎间盘退变的潜力。然而，在椎间盘内注射期间，即使在水凝胶载体存在的情况下，绝大多数细胞也会泄漏出来。最近的证据表明，环状穿刺术与细胞渗漏有关，并有助于骨赘的形成，这是一种令人不快的副作用。这提示开发合适的载体用于MSCs的盘内输送具有重要意义。我们之前开发了一种胶原微胶囊平台，将MSCs包裹在由胶原纳米纤维网络组成的固体微球中。这些固体但多孔的微球支持MSC的附着、存活、增殖、迁移、分化和基质重塑。在这里，我们假设在胶原微球内注射间充质干细胞将在更好的功能结果和减少副作用方面优于生理盐水中的间充质干细胞。具体地说，我们诱导了兔的椎间盘退变，然后将包裹在胶原微球中或直接悬浮在生理盐水中的自体MSCs注入不同水平的椎间盘。定期监测功能结果，包括水化指数和椎间隙高度，直到6个月。处死后，取受累椎间盘进行组织学、生物化学和生物力学评价。胶原蛋白微球中的MSCs在维持动态力学行为方面优于生理盐水中的MSCs，但在水化、维持椎间盘高度和基质组成方面表现相似。更重要的是，根据大体外观、X线片和组织学检查，与生理盐水相比，胶原微球中运送MSCs显著降低了骨赘形成的风险。这项工作证明了在椎间盘内注射MSCs的过程中使用细胞载体在治疗椎间盘退变中的意义。
Mesenchymal stem cells (MSCs) have the potential to treat early intervertebral disc (IVD) degeneration. However, during intradiscal injection, the vast majority of cells leaked out even in the presence of hydrogel carrier. Recent evidence suggests that annulus puncture is associated with cell leakage and contributes to osteophyte formation, an undesirable side effect. This suggests the significance of developing appropriate carriers for intradiscal delivery of MSCs. We previously developed a collagen microencapsulation platform, which entraps MSCs in a solid microsphere consisting of collagen nanofiber meshwork. These solid yet porous microspheres support MSC attachment, survival, proliferation, migration, differentiation, and matrix remodeling. Here we hypothesize that intradiscal injection of MSCs in collagen microspheres will outperform that of MSCs in saline in terms of better functional outcomes and reduced side effects. Specifically, we induced disc degeneration in rabbits and then intradiscally injected autologous MSCs, either packaged within collagen microspheres or directly suspended in saline, into different disc levels. Functional outcomes including hydration index and disc height were monitored regularly until 6 months. Upon sacrifice, the involved discs were harvested for histological, biochemical, and biomechanical evaluations. MSCs in collagen microspheres showed advantage over MSCs in saline in better maintaining the dynamic mechanical behavior but similar performance in hydration and disc height maintenance and matrix composition. More importantly, upon examination of gross appearance, radiograph, and histology of IVD, delivering MSCs in collagen microspheres significantly reduced the risk of osteophyte formation as compared to that in saline. This work demonstrates the significance of using cell carriers during intradiscal injection of MSCs in treating disc degeneration.