(W1030-10-63) Atraumatic Access to Xenograft Human Glioblastoma by Cerebral Open Flow Microperfusion

Purpose: Orthotopic xenograft studies strongly promote the development of personalized cancer therapies and can thereby improve the still poor life expectancy of glioblastoma patients. Recently, the tumor microenvironment has increasingly become subject of investigations, as it may have an impact on the cancer progression. However, investigation of the tumor microenvironment with currently available methods inevitably causes trauma that can compromise the reliability of the obtained data. We therefore aimed to implement an atraumatic access to human xenograft glioblastoma with cerebral Open Flow Microperfusion (cOFM) by implantation of xenograft cells in rodent’s brain with intact blood brain barrier (BBB), and subsequent development of a xenograft glioblastoma at the interface between the cOFM probe and the surrounding brain tissue.

Methods: In vitro: Human glioma cells (U87MG) were perfused through the cOFM probe setup at different concentrations and with different flow rates and the glioma cells were then collected in cell culture medium (Dulbecco's Modified Eagle's Medium, DMEM). Their viability after passage through the cOFM probe was tested by Höchst staining and count of living cells 48 hours after having passed the cOFM probe. In vivo: Human glioma cells (U87MG or U118MG) were implanted into the striatum of immune-deficient rodent’s brain via cOFM or via syringe. The tumor growth was monitored over 21 days by magnetic resonance imaging and characteristics of the mature tumors were histologically assessed.

Results: In vitro: More than 96% of human glioma cells survived the passage through the cOFM probe. In vivo: Xenograft glioma cells were successfully implanted into rodent brain with intact BBB by means of cOFM probes. Histological assessments confirmed that the tumor tissue that developed around the cOFM probe was unaffected by the presence of the probe, thus creating an atraumatic access to the tumor. The mature cOFM-induced tumors resembled the syringe-induced ones and showed typical features of human glioblastoma such as palisading nuclei.

Conclusion: A novel atraumatic access to human glioblastoma in rodent was created which provides the possibility to collect interstitial fluid from functional tumor tissue in vivo without trauma generation. Thereby, reliable data can be generated that are strongly promoting drug research, biomarker identification, and enabling investigation of the BBB of a functional tumor.

Acknowledgements: The authors declare no conflict of interest.
All experiments with animals were performed in accordance with the EU Directive 2010/63/EU and with permission of the Federal Ministry of Education, Science and Research of the Republic of Austria under the animal application number BMWFW-66.010/0071-WF/V/3b/2017 and 2022-0.429.379.