Umbilical cord‐derived mesenchymal stromal/stem cells expressing IL‐24 induce apoptosis in gliomas

• Published in: Journal of cellular physiology 2020-02, Vol.235 (2), p.1769-1779
• Main Authors: Fan, Shaochen, Gao, Huasong, Ji, Wei, Zhu, Fengwei, Sun, Lingzheng, Liu, Yuankun, Zhang, Siming, Xu, Yanran, Yan, Yaohua, Gao, Yilu
• Format: Article
• Language: English
• Subjects: Apoptosis; Brain tumors; Cell migration; Cell proliferation; Complementary DNA; Deoxyribonucleic acid; DNA; Fluorescence; Gene therapy; Glioma; Glioma cells; Green fluorescent protein; Immunoregulation; Interleukin 24; Interleukin 24 (IL‐24); Mesenchyme; Stem cells; Tumor cells; Tumors; Umbilical cord; umbilical cord‐derived mesenchymal stromal/stem cells (UC‐MSCs); Xenografts; Xenotransplantation
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29095

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. Umbilical cord‐derived mesenchymal stromal/stem cells (UC‐MSCs) show the ability to migrate to glioma cells in vitro and in vivo. In addition, UC‐MSCs modified to express IL‐24 show an antitumor effect in the treatment of gliomas.