Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA.
J Biomed Mater Res A. 2021 Jul;109(7):1247-1255. doi: 10.1002/jbm.a.37118. Epub 2020 Oct 16.
In multiple sclerosis (MS), abnormally activated immune cells responsive to myelin proteins result in widespread damage throughout the central nervous system (CNS) and ultimately irreversible disability. Immunomodulation by delivering dendritic cells (DCs) utilizes a potent and rapid MS disease progression driver therapeutically. Here, we investigated delivering DCs for disease severity attenuation using an experimental autoimmune encephalomyelitis preclinical MS model. DCs treated with interleukin-10 (IL-10) (DC10s) were transplanted using in situ gelling poly(ethylene glycol)-based hydrogel for target site localization. DC delivery increased hydrogel longevity and altered the injection site recruited, endogenous immune cell profile within 2 days postinjection. Furthermore, hydrogel-mediated DC transplantation efficacy depended on the injection-site. DCs delivered to the neck local to MS-associated CNS-draining cervical lymph nodes attenuated paralysis, compared to untreated controls, while delivery to the flank did not alter paralysis severity. This study demonstrates that local delivery of DC10s modulates immune cell recruitment and attenuates disease progression in a preclinical model of MS.
在多发性硬化症 (MS) 中，对髓鞘蛋白有反应的异常激活免疫细胞会导致中枢神经系统 (CNS) 广泛受损，最终导致不可逆转的残疾。通过递送树突状细胞 (DC) 进行免疫调节是一种有效的、快速的 MS 疾病进展驱动治疗方法。在这里，我们使用实验性自身免疫性脑脊髓炎 (EAE) 临床前 MS 模型研究了使用 DC 来减轻疾病严重程度。用白细胞介素 10 (IL-10) 处理的 DC (DC10) 使用原位凝胶化聚乙二醇 (PEG) 基水凝胶进行移植，以实现靶向定位。DC 递送增加了水凝胶的寿命，并在注射后 2 天内改变了注射部位招募的内源性免疫细胞特征。此外，水凝胶介导的 DC 移植效果取决于注射部位。与未治疗的对照组相比，将 DC 递送到颈部局部 MS 相关的 CNS 引流颈淋巴结可减轻瘫痪，而将 DC 递送到侧腹则不会改变瘫痪的严重程度。这项研究表明，在 MS 的临床前模型中，局部递送电刺激 DC10 可调节免疫细胞募集并减轻疾病进展。
