Abstract

Oncolytic Targets Identified by Genetically Engineered hNSCs in a Rodent Model of Spinal Cord Glioma

Yang Teng, Associate Professor, Harvard Medical School

We have developed a rat model of intramedullary spinal cord gliomas (ISCG) and determined whether genetically engineered human neural stem cells (hNSC) could be developed into potent therapies for ISCG. ISCG rats received injection of hNSC.CD-TK, hNSC.CD or hNSC.CD-TK debris adjacent to the tumor epicenter 7 days after glioma cell implantation, followed with daily prodrug administration (5-FC and GCV; i.p. throughout the study). Post-tumor survival was assessed by time lasted before loss of body weight-bearing stepping in the hindlimb. Also evaluated were autonomic functions and tumor growth rate in vivo. ISCG rats with hNSC.CD-TK treatment showed significantly improved survival than controls that received hNSC.CD or hNSC.CD-TK debris (P < 0.05, median rank test), with better maintained autonomic function and reduced tumor growth rate. hNSC.CD-TK cells migrated diffusively into ISCG clusters to mediate targeted oncolytic effect in manners that spared spinal cord projection pathways. Through impeding glioma growth and preserving spinal cord neurobiology, dual gene-engineered hNSC regimen significantly prolonged survival in a rat model that emulated sensorimotor and autonomic dysfunctions of human cervical ISCG. Our findings may provide a stem cell-based multimodal approach to treating ISCG and help formulate a recovery neurobiology-based therapeutic strategy for gliomas.