Shendi Dalia, Albrecht Dirk R, Jain Anjana
Nano-Neural Therapeutics Laboratory, Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts.
Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts.
J Biomed Mater Res A. 2017 Feb;105(2):608-618. doi: 10.1002/jbm.a.35930. Epub 2016 Nov 18.
Central nervous system (CNS) injuries and diseases result in neuronal damage and loss of function. Transplantation of neural stem cells (NSCs) has been shown to improve locomotor function after transplantation. However, due to the immune and inflammatory response at the injury site, the survival rate of the engrafted cells is low. Engrafted cell viability has been shown to increase when transplanted within a hydrogel. Hyaluronic acid (HA) hydrogels have natural anti-inflammatory properties and the backbone can be modified to introduce bioactive agents, such as anti-Fas, which we have previously shown to promote NSC survival while suppressing immune cell activity in bulk hydrogels in vitro. Although bulk HA hydrogels have shown to promote stem cell survival, microsphere gels for NSC encapsulation and delivery may have additional advantages. In this study, a flow-focusing microfluidic device was used to fabricate either vinyl sulfone-modified HA (VS-HA) or anti-Fas-conjugated HA (anti-Fas HA) microsphere gels encapsulated with NSCs. The majority of encapsulated NSCs remained viable for at least 24 h in the VS-HA and anti-Fas HA microsphere gels. Moreover, T-cells cultured in suspension with the anti-Fas HA microsphere gels had reduced viability after contact with the microsphere gels compared to the media control and soluble anti-Fas conditions. This approach can be adapted to encapsulate various cell types for therapeutic strategies in other physiological systems in order to increase survival by reducing the immune response. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 608-618, 2017.
中枢神经系统（CNS）损伤和疾病会导致神经元损伤和功能丧失。神经干细胞（NSCs）移植已被证明可改善移植后的运动功能。然而，由于损伤部位的免疫和炎症反应，移植细胞的存活率较低。当在水凝胶中移植时，已证明移植细胞的活力会增加。透明质酸（HA）水凝胶具有天然的抗炎特性，其主链可以被修饰以引入生物活性剂，如抗Fas，我们之前已证明这种生物活性剂在体外的块状水凝胶中可促进神经干细胞存活，同时抑制免疫细胞活性。尽管块状HA水凝胶已显示出可促进干细胞存活，但用于神经干细胞封装和递送的微球凝胶可能具有其他优势。在本研究中，使用流动聚焦微流控装置制备了包裹有神经干细胞的乙烯砜改性HA（VS-HA）或抗Fas共轭HA（抗Fas HA）微球凝胶。大多数包裹在VS-HA和抗Fas HA微球凝胶中的神经干细胞至少在24小时内保持存活。此外，与培养基对照和可溶性抗Fas条件相比，与抗Fas HA微球凝胶悬浮培养的T细胞在与微球凝胶接触后活力降低。这种方法可适用于封装各种细胞类型，用于其他生理系统的治疗策略，以通过减少免疫反应来提高存活率。©2016威利期刊公司。《生物医学材料研究杂志》A部分：105A：608 - 618，2017年。
