Engineering stem cells to secrete enzymes for the conversion of prodrugs. A) Diagram of CD-expressing NSCs localized to tumor cells, and CD conversion of 5-FC to 5-FU, which readily diffuses out of the NSCs to selectively kill the surrounding tumor cells. B,C) H&E-stained brain tumor sections from U251 glioma–bearing mice that received HB1.F3.CD NSCs only (B) or HB1.F3.CD NSCs in combination with 5-FC (C). White arrows indicate tumor region. Reproduced with permission.[282] Copyright 2013, Science. D) Brain injection of NSC1-tk cells coupled with GCV treatment prolonged the life of mice inoculated with U87 glioma cells. Statistical analysis was performed using the log rank test. E) Representative pictures of brain sections show the tumor size of different groups. NSC1-tk brain injection followed by GCV i.p. injection appears to shrink the tumor. Reproduced with permission.[280] Copyright 2012, Nature.