Forced expression of indoleamine-2,3-dioxygenase in human umbilical cord-derived mesenchymal stem cells abolishes their anti-apoptotic effect on leukemia cell lines in vitro

• Published in: In vitro cellular & developmental biology. Animal 2013-12, Vol.49 (10), p.752-758
• Main Authors: Yuan, Yin, Lu, Xin, Tao, Chang-li, Chen, Xuan, Shao, Hong-wei, Huang, Shu-lin
• Format: Article
• Language: English
• Subjects: Adenovirus; adverse effects; Analysis of Variance; Animal Genetics and Genomics; Apoptosis; Apoptosis - physiology; Biomedical and Life Sciences; Blotting, Western; Bone marrow; Cell Biology; Cell Culture; Cell Culture Techniques - methods; Cell Line, Tumor; Cell lines; cell proliferation; Chinese culture; Cloning, Molecular; complementary DNA; Cultured cells; Developmental Biology; DNA, Complementary - genetics; Flow Cytometry; Gene Expression Regulation, Enzymologic - physiology; genes; genetic vectors; Hematopoietic stem cells; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; kynurenine; Leukemia; Life Sciences; lymphocytes; Mesenchymal stem cells; Mesenchymal Stromal Cells - enzymology; Mesenchymal Stromal Cells - metabolism; Stem Cells; Stromal cells; T lymphocytes; Umbilical Cord - cytology; viruses
• ISSN: 1071-2690; 1543-706X
• DOI: 10.1007/s11626-013-9667-4

The ability of mesenchymal stem cells (MSCs) to preserve cancer cells potentially constitutes the adverse effect of MSC-based cell therapy in the context of hematologic malignancy. In an effort to reverse this undesirable feature of MSCs, we manipulated human umbilical cord-derived MSCs (UC-MSCs) to express indoleamine-2,3-dioxygenase (IDO), an enzyme that induces immune suppression by inhibiting T cell proliferation and triggering apoptosis in immune cells. Cultures of human UC-MSCs were generated by plastic adherence method. Full-length cDNA of human IDO was cloned into adenovirus shuttle vector. Then, the recombinant virus harboring IDO gene was produced in 293 cells and used to infect UC-MSCs. Expression of IDO protein was detected within infected UC-MSCs, and accumulation of kynurenine was observed in the supernatant. Two human leukemia cell lines, Jurkat and HL-60, were cultured on the monolayer of native or infected UC-MSCs, respectively. It was observed that forced IDO expression abolished the anti-apoptotic effect of UC-MSCs on these leukemia cells and enhanced their proliferation inhibitory effect on activated human lymphocytes as well as leukemia cells. These results suggested that equipping MSCs with IDO could be one of the reasonable strategies to reverse their cancer-supportive effect unfavorable for clinical applications.