Optimized creation of glioblastoma patient derived xenografts for use in preclinical studies.
Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in adults, highlighting the need for novel treatment strategies. Patient derived xenografts (PDX) represent a valuable tool to accomplish this task.



PDX were established by implanting GBM tissue subcutaneously. Engraftment success was compared between NMRI Foxn1nuand NOD/SCID as well as between fresh and cryopreserved tissue. Established PDX were analyzed histologically and molecularly. Five PDX were experimentally treated with different drugs to assess their potential for preclinical drug testing.



Establishment of PDX was attempted for 36 consecutive GBM cases with an overall success rate of 22.2% in NMRI Foxn1numice. No difference was observed between fresh or cryopreserved (20-1057 days) tissue in direct comparison (n = 10 cases). Additionally, engraftment was better in NOD/SCID mice (38.8%) directly compared to NMRI Foxn1numice (27.7%) (n = 18 cases). Molecular data and histology of the PDX compare well to the primary GBM. The experimental treatment revealed individual differences in the sensitivity towards several clinically relevant drugs.



The use of vitally frozen GBM tissue allows a more convenient workflow without efficiency loss. NOD/SCID mice appear to be better suited for initial engraftment of tumor tissue compared to NMRI Foxn1numice.
Children's Hospital, University Medicine Rostock, Ernst-Heydemann-Str. 8, 18057, Rostock, Germany.
Doreen
D
William
Department of Surgery, Molecular Oncology and Immunotherapy, University Medicine Rostock, Schillingallee 35, 18057, Rostock, Germany.
Christina Susanne
CS
Mullins
Institute of Pathology, University Medicine Rostock, Strempelstr. 14, 18057, Rostock, Germany.
Björn
B
Schneider
Experimental Pharmacology and Oncology Berlin-Buch GmbH, Robert-Roessle-Str. 10, 13125, Berlin-Buch, Germany.
Andrea
A
Orthmann
Institute of Pathology, University Medicine Rostock, Strempelstr. 14, 18057, Rostock, Germany.
Nora
N
Lamp
Department of Surgery, Molecular Oncology and Immunotherapy, University Medicine Rostock, Schillingallee 35, 18057, Rostock, Germany.
Mathias
M
Krohn
Experimental Pharmacology and Oncology Berlin-Buch GmbH, Robert-Roessle-Str. 10, 13125, Berlin-Buch, Germany.
Annika
A
Hoffmann
Children's Hospital, University Medicine Rostock, Ernst-Heydemann-Str. 8, 18057, Rostock, Germany.
Carl-Friedrich
CF
Classen
Department of Surgery, Molecular Oncology and Immunotherapy, University Medicine Rostock, Schillingallee 35, 18057, Rostock, Germany. michael.linnebacher@med.uni-rostock.de.
Michael
M
Linnebacher
D000328:Adult; D000368:Aged; D000818:Animals; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D013194:Staining and Labeling; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
Engraftment rate; Glioblastoma multiforme; PDX; Preclinical mouse models; Therapy