Atraumatic access to human glioblastoma in a xenograft animal model by cerebral open flow microperfusion

Orthotopic xenograft studies promote the development of targeted/personalized therapies to improve the still poor life expectancy of glioblastoma patients.

We implemented an atraumatic access to glioblastoma with cerebral Open Flow Microperfusion (cOFM) by implantation of xenograft cells in rat brain with intact blood brain barrier (BBB) and subsequent development of a xenograft glioblastoma at the interface between the cOFM probe and surrounding brain tissue. Human glioma U87MG cells were implanted at a well-defined position into immunodeficient Rowett nude rat´s brain via cOFM (cOFM group) and syringe (control group). Characteristics of the mature tumors from both groups were assessed.

For the first time xenograft cells were successfully introduced into rat brain with intact BBB using cOFM, and the tumor tissue developing around the cOFM probe was unaffected by the presence of the probe. Thereby an atraumatic access to the tumor was created. The success rate of glioblastoma development in the cOFM group was high (>70%). The mature cOFM-induced tumors (20-23 days after cell-implantation) resembled the syringe-induced ones and showed typical features of human glioblastoma.

Examining xenograft tumor microenvironment with currently available methods inevitably causes trauma that could affect the reliability of obtained data.

This novel atraumatic access to human glioblastoma in rat brain provides the possibility to collect interstitial fluid from functional tumor tissue in vivo without trauma generation. Thereby, reliable data can be generated promoting drug research, biomarker identification, and enabling investigation of the BBB of an intact tumor.