Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.
Mol Neurobiol. 2022 Jun;59(6):3449-3457. doi: 10.1007/s12035-022-02774-x. Epub 2022 Mar 24.
We used recombinant interleukin 23 receptor (RIL-23R)-engineered mesenchymal stem cells (MSCs) to study its therapeutic role in enhancing inflammation of nervous tissue in the mouse model (EAE) of multiple sclerosis (MS). Recombinant IL-23 receptor construct was designed to enter MSCs. The bioactivity of the constructs was assessed by the co-culture of MSCs/CD4 + T cells. The EAE model was induced in mice. After cell transplantation, clinical scores were evaluated, and tissue demyelination was measured by Luxol fast blue staining. The transfection of RIL-23R mRNA improved MSC properties significantly to the inflamed regions of EAE mice, and it performed an increased suppressive function on the T lymphocyte proliferation. Furthermore, in vivo therapy with RIL-23R MSCs in EAE mice showed an enhanced therapeutic action than MSCs, proven by improved myelination and a reduction in the penetration of inflammatory cells into the white matter. Our targeted transplantation procedure of modified MSC can be applied to improve the effectiveness of cellular therapy for multiple sclerosis and other autoimmune disorders.
我们使用重组白细胞介素 23 受体（RIL-23R）工程间充质干细胞（MSCs）来研究其在增强多发性硬化症（MS）小鼠模型（EAE）中神经组织炎症中的治疗作用。设计了重组 IL-23 受体构建体以进入 MSCs。通过 MSC/CD4+T 细胞共培养评估构建体的生物活性。在小鼠中诱导 EAE 模型。细胞移植后，评估临床评分，并通过卢索快速蓝染色测量组织脱髓鞘。RIL-23R mRNA 的转染显着改善了 MSC 特性，使其进入 EAE 小鼠的炎症区域，并对 T 淋巴细胞增殖具有增强的抑制作用。此外，EAE 小鼠中 RIL-23R MSC 的体内治疗显示出比 MSC 更强的治疗作用，这可通过改善髓鞘形成和减少炎症细胞渗透到白质来证明。我们改良的 MSC 靶向移植程序可用于提高细胞治疗多发性硬化症和其他自身免疫性疾病的有效性。
