Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, China.
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
J Cell Physiol. 2020 Feb;235(2):1769-1779. doi: 10.1002/jcp.29095. Epub 2019 Jul 12.
Although much progress has been made in the treatment of gliomas, the prognosis for patients with gliomas is still very poor. Stem cell-based therapies may be promising options for glioma treatment. Recently, many studies have reported that umbilical cord-derived mesenchymal stromal/stem cells (UC-MSCs) are ideal gene vehicles for tumor gene therapy. Interleukin 24 (IL-24) is a pleiotropic immunoregulatory cytokine that has an apoptotic effect on many kinds of tumor cells and can inhibit the growth of tumors specifically without damaging normal cells. In this study, we investigated UC-MSCs as a vehicle for the targeted delivery of IL-24 to tumor sites. UC-MSCs were transduced with lentiviral vectors carrying green fluorescent protein (GFP) or IL-24 complementary DNA. The results indicated that UC-MSCs could selectively migrate to glioma cells in vitro and in vivo. Injection of IL-24-UC-MSCs significantly suppressed tumor growth of glioma xenografts. The restrictive efficacy of IL-24-UC-MSCs was associated with the inhibition of proliferation as well as the induction of apoptosis in tumor cells. These findings indicate that UC-MSC-based IL-24 gene therapy may be able to suppress the growth of glioma xenografts, thereby suggesting possible future therapeutic use in the treatment of gliomas.
尽管在治疗神经胶质瘤方面已经取得了很大的进展，但神经胶质瘤患者的预后仍然非常差。基于干细胞的治疗方法可能是治疗神经胶质瘤的有前途的选择。最近，许多研究报告称，脐带间充质基质/干细胞（UC-MSCs）是肿瘤基因治疗的理想基因载体。白细胞介素 24（IL-24）是一种多效免疫调节细胞因子，对多种肿瘤细胞具有凋亡作用，能够特异性抑制肿瘤生长而不损伤正常细胞。在这项研究中，我们研究了 UC-MSCs 作为靶向递送至肿瘤部位的 IL-24 的载体。UC-MSCs 被携带绿色荧光蛋白（GFP）或 IL-24 cDNA 的慢病毒载体转导。结果表明，UC-MSCs 可以在体外和体内选择性地迁移至神经胶质瘤细胞。IL-24-UC-MSCs 的注射显著抑制了神经胶质瘤异种移植物的生长。IL-24-UC-MSCs 的限制作用与肿瘤细胞增殖的抑制以及凋亡的诱导有关。这些发现表明，基于 UC-MSC 的 IL-24 基因治疗可能能够抑制神经胶质瘤异种移植物的生长，从而为治疗神经胶质瘤提供未来可能的治疗用途。
