In vitro effect of adenovirus-mediated human Gamma Interferon gene transfer into human mesenchymal stem cells for chronic myelogenous leukemia
✍ Scribed by XiaoQing Li; Yue Lu; WenLin Huang; HaiPeng Xu; XiaoQin Chen; QiRong Geng; HuiJie Fan; YinDuo Tan; Gang Xue; XiangLi Jiang
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 331 KB
- Volume
- 24
- Category
- Article
- ISSN
- 0278-0232
- DOI
- 10.1002/hon.779
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
For developing gene therapy for chronic myelogenous leukemia (CML), we evaluated the feasibility of using autologous bone marrow stromal cells (BMSCs) of one CML patient as a target cell population and studied the efficiency of recombinant adenovirus‐mediated human Gamma Interferon (hIFN‐γ) gene transfer into BMSCs. BMSCs can be readily obtained, expanded, and successfully transduced with adenoviral vectors in vitro. We studied the in vitro expression of hIFN‐γ in human BMSCs following transduction with Ad/hIFN‐γ. On transduction of BMSCs at a MOI of 50, the expression and secretion of hIFN‐γ were achieved as high as 5492 ± 660∼50647 ± 4049 ng/10^6^ cells per 24 h over the course of 3 weeks. We further studied the effects of hIFN‐γ produced by transduced BMSCs on the proliferation of the human leukemia cell line K562 cells in vitro, proliferation of K562 cells was markedly inhibited in the experimental groups as compared with the other two control groups after 5 days of coculture. We also found that the percentage of K562 cells in the G~1~ phase of cell cycle can be increased by treatment of hIFN‐γ produced by Ad/hIFN‐γ transduced BMSCs, but the percentage of K562 cells in the S phase of cell cycle can be decreased in the same time. Apoptosis rate of K562 cells in the experimental groups was 30.8 ± 8.5%, as compared with the other two control groups (5.6 ± 1.3% and 5.5 ± 0.8%, respectively) (p < 0.01). Our results indicate that hIFN‐γ gene engineered BMSCs of CML donors could be successfully established and that local production of hIFN‐γ is sufficiently to inhibit the proliferation of K562 cells and induce apoptosis of K562 cells in vitro, suggesting an important potential use in the clinical gene therapy of CML. Copyright © 2006 John Wiley & Sons, Ltd.