Table 8 Advantages and disadvantages of various models for meningiomas

Heterotopic xenograft

Implantation/xenografting of either cells or whole tumor pieces in a site other than intracranial/intraspinal

• Flank/subcutaneous

Implantation/xenografting of either cells or whole tumor pieces subcutaneously either via scalpel or injection. Matrigel can be utilized for a fixed position

Easy to implant, easy to measure and follow growth, inexpensive

Caliper measurements are estimates due to artefacts from skin and fatty tissue

• Subrenal

Surgically implantation of cells in the subrenal capsule. For technique see [127]

More accurate measurements compared to subcutaneous technique

Implantation and measurements require surgery and strain of the animals

Orthotopic xenograft

Implantation/xenografting of either cells or whole tumor pieces at dura attached areas intracranially and intraspinally

• Superficial

Implantation superficially most often through a burr hole in the frontal region

Easy to locate, low risk of bleeding perioperatively

Risk of cell reflux, if not careful

• Skull base

Implantation at the skull base most often through a burr hole in the frontal region

Fixed position, low risk of cell reflux

Depending on head angle of animals during implantation different placements on skull base

Higher risk of bleeding

• Post-glenoid foramen

Natural cavity in rodents

Located on the rostral area of the opening of the external acoustic meatus

Different angles for different sites from cerebrum, cerebellum to brain stem and basal cistern [182]

Can be performed via subcutaneous injection, short procedure time, accessible to researchers without surgical skills [182]

Requires a sharp needle, increased risk of bleeding, handheld injection

Xenografted material

• The use of patient-derived primary material

Patient-derived samples obtained through surgery without immortalization. Benign tumors in particular are prone to senescence

Recapitulates each individual tumor more accurately to be used in personal targeted therapy

Varying TTRs between and within each patient derived tumor

Mix of host DNA and human xenograft

• Using cell suspension

Injection of a suspension of cells

Easy to control number of cells used. Produces similar conditions for all animals in drug trials

Has to develop from cell suspension to tumor -Morphological changes can occur

Only most viable cells survive culture

• Using whole tumor pieces

Implantation of whole tumor pieces from surgical specimens

Xenograft is morphologically representable to parent tumor

Difficult to make sure representable pieces of tumor is implanted and that it is consistent throughout animals

• The use of established/commercially available material

Immortalized patient-derived cells

Often purchasable through biobanks or cell companies such as ATCC (American Type Culture Collection)

Near 100% tumor-take rate—need for a small number of animals

Homogeneous tumors across all studies

Can perform genomic alterations to cells to study differences [79]

Growth patterns do not represent primary meningiomas due to immortalization and homogenous cell population

• Syngeneic cell implantation

Use of cells deriving from the same species—in this setting murine meningioma to murine host

High tumor-take rate in immunocompetent animals

Assessment of mice derived tumors—Possible problems in translating to humans

Genetically Engineered Models

Knock-out or knock-in of genes through genetic manipulation (i.e. Cre-recombinase or RCAS/TVA)

Valuable tools for preclinical drug testing and for studying the underlying oncogenic drivers and molecular pathways in tumors

Expensive, labor intensive, other pathologies connected to genetic lesion

Corneal implantation

Implantation of tumor material in corneal pocket

Easy assessment of vessel growth through fundoscopy

Heterotopic model, loss of microenvironment