Abstract
ObjectiveIn this work we set to develop and to validate a new in vivo frameless orthotopic Diffuse Intrinsic Pontine Glioma (DIPG) model based in the implantation of a guide-screw system.MethodsIt consisted of a guide-screw also called bolt, a Hamilton syringe with a 26-gauge needle and an insulin-like 15-gauge needle. The guide screw is 2.6 mm in length and harbors a 0.5 mm central hole which accepts the needle of the Hamilton syringe avoiding a theoretical displacement during insertion. The guide-screw is fixed on the mouse skull according to the coordinates: 1mm right to and 0.8 mm posterior to lambda. To reach the pons the Hamilton syringe is adjusted to a 6.5 mm depth using a cuff that serves as a stopper. This system allows delivering not only cells but also any kind of intratumoral chemotherapy, antibodies or gene/viral therapies.ResultsThe guide-screw was successfully implanted in 10 immunodeficient mice and the animals were inoculated with DIPG human cell lines during the same anesthetic period. All the mice developed severe neurologic symptoms and had a median overall survival of 95 days ranging the time of death from 81 to 116 days. Histopathological analysis confirmed tumor into the pons in all animals confirming the validity of this model.ConclusionHere we presented a reproducible and frameless DIPG model that allows for rapid evaluation of tumorigenicity and efficacy of chemotherapeutic or gene therapy products delivered intratumorally to the pons.
Highlights
We presented a reproducible and frameless Diffuse Intrinsic Pontine Glioma (DIPG) model that allows for rapid evaluation of tumorigenicity and efficacy of chemotherapeutic or gene therapy products delivered intratumorally to the pons
Diffuse Intrinsic Pontine Gliomas (DIPGs) represent the most frequent tumor among brainstem gliomas and constitute a real challenge for everyone devoted to the treatment of pediatric brain tumors[1,2]
To validate the development of a frameless reproducible brainstem tumor model we injected the DIPG TP54 cells using our guide-screw system into the pons of nude mice (N = 10) according to the protocol described above
Summary
Diffuse Intrinsic Pontine Gliomas (DIPGs) represent the most frequent tumor among brainstem gliomas and constitute a real challenge for everyone devoted to the treatment of pediatric brain tumors[1,2]. Unlike other brainstem tumors that benefit from surgical treatment such as focal pontine gliomas, exophytic, tectal or cervicomedullary tumors, DIPG due to its diffuse nature and anatomic extension within the pons, remains a fatal neoplasm[4]. The main advantage of using stereotaxy consists of precise access to the pons region throughout a biopsy needle aimed to a specific region in the brainstem according to previous standard coordinates. To perform studies with a high number of animals, such as survival studies with new therapeutic strategies or delivery of gene therapy agents, which need to be injected intratumorally, stereotaxy is extremely time-consuming, even in the hands of experienced researchers. If serial subsequent injections need to be performed there is the risk that they do not fall exactly in the same place
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