期刊
STEM CELLS AND DEVELOPMENT
卷 25, 期 12, 页码 897-908出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2015.0324
关键词
-
资金
- Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A120446]
- Seoul National University Hospital Research Fund [30-2014-0270]
Stem-cell based gene therapy is a promising novel therapeutic approach for inoperable invasive tumors, including brainstem glioma. Previously, we demonstrated the therapeutic potential of human adipose tissue-derived mesenchymal stem cells (hAT-MSC) genetically engineered to express a secreted form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) against brainstem glioma. However, safety concerns should be comprehensively investigated before clinical applications of hAT-MSC. sTRAIL. At first, we injected stereotactically low (1.2 x 10(5) cells/18 mu L), medium (2.4 x 10(5)/18 mu L), or high dose (3.6 x 10(5)/18 mu L) of hAT-MSC. sTRAIL into the brainstems of immunodeficient mice reflecting the plan of the future clinical trial. Local toxicity, systemic toxicity, secondary tumor formation, and biodistribution of hAT-MSC. sTRAIL were investigated. Next, presence of hAT-MSC. sTRAIL was confirmed in the brain and major organs at 4, 9, and 14 weeks in brainstem glioma-bearing mice. In the 15-week subchronic toxicity test, no serious adverse events in terms of body weight, food consumption, clinical symptom, urinalysis, hematology, clinical chemistry, organ weight, and histopathology were observed. In the 26-week tumorigenicity test, hAT-MSC. sTRAIL made no detectable tumors, whereas positive control U-87 MG cells made huge tumors in the brainstem. No remaining hAT-MSC. sTRAIL was observed in any organs examined, including the brainstem at 15 or 26 weeks. In brainstem glioma-bearing mice, injected hAT-MSC. sTRAIL was observed, but gradually decreased over time in the brain. The mRNA of human specific GAPDH and TRAIL was not detected in all major organs. These results indicate that the hAT-MSC. sTRAIL could be applicable to the future clinical trials in terms of biosafety.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据