Use of Tissue Specimens from Stereotactic Biopsies for Patient-Derived GBM Organoid-Based Drug Testing

<i>IDH</i>-wildtype glioblastoma (GBM) represents the most common malignant form of brain tumor and is still incurable despite comprehensive therapeutic efforts. Due to tumor location and patient condition, open surgical resection of recurrent GBM is not always feasible. In these cases,...

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Main Authors: Amélie Wöllner, Adrian Paul, Maddalena Arquilla, Junguo Cao, Catharina Lotsch, Gerhard Jungwirth, Lena Jassowicz, Andreas von Deimling, Andreas W. Unterberg, Sandro M. Krieg, Martin Jakobs, Rolf Warta, Christel Herold-Mende
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Language:English
Published: MDPI AG 2025-05-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/10/701
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author Amélie Wöllner
Adrian Paul
Maddalena Arquilla
Junguo Cao
Catharina Lotsch
Gerhard Jungwirth
Lena Jassowicz
Andreas von Deimling
Andreas W. Unterberg
Sandro M. Krieg
Martin Jakobs
Rolf Warta
Christel Herold-Mende
author_facet Amélie Wöllner
Adrian Paul
Maddalena Arquilla
Junguo Cao
Catharina Lotsch
Gerhard Jungwirth
Lena Jassowicz
Andreas von Deimling
Andreas W. Unterberg
Sandro M. Krieg
Martin Jakobs
Rolf Warta
Christel Herold-Mende
author_sort Amélie Wöllner
collection DOAJ
description <i>IDH</i>-wildtype glioblastoma (GBM) represents the most common malignant form of brain tumor and is still incurable despite comprehensive therapeutic efforts. Due to tumor location and patient condition, open surgical resection of recurrent GBM is not always feasible. In these cases, frame-based stereotactic biopsies represent a less invasive technique to obtain tissue samples for diagnostics. However, whether this material would also be sufficient to prepare tumor organoids (TOs) and perform drug screenings has not been addressed so far. In this study, we present our highly optimized workflow for generating standardized patient-derived GBM TOs from single-cell suspensions using limited biopsy-derived material. We highlight crucial steps within the procedure, such as reliable cell counting, viable cell recovery, enzymatic digestion, and the requirement of an extracellular matrix as a scaffold. Furthermore, we showcase the potential of personalized drug testing as a promising application of GBM TOs. In conclusion, we successfully developed a robust workflow that effectively utilizes the limited material derived from stereotactic biopsies to reproducibly form standardized TOs. Moreover, we demonstrate that biopsy-derived TOs represent a valuable tool for testing drug vulnerabilities in a personalized setting, which might be especially useful in the case of non-resectable GBM.
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spelling doaj-art-a263c54aea784834bf13768d35e09a8a2025-08-20T03:47:53ZengMDPI AGCells2073-44092025-05-01141070110.3390/cells14100701Use of Tissue Specimens from Stereotactic Biopsies for Patient-Derived GBM Organoid-Based Drug TestingAmélie Wöllner0Adrian Paul1Maddalena Arquilla2Junguo Cao3Catharina Lotsch4Gerhard Jungwirth5Lena Jassowicz6Andreas von Deimling7Andreas W. Unterberg8Sandro M. Krieg9Martin Jakobs10Rolf Warta11Christel Herold-Mende12Division of Experimental Neurosurgery, Department of Neurosurgery, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Experimental Neurosurgery, Department of Neurosurgery, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Experimental Neurosurgery, Department of Neurosurgery, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Experimental Neurosurgery, Department of Neurosurgery, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Experimental Neurosurgery, Department of Neurosurgery, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Experimental Neurosurgery, Department of Neurosurgery, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Experimental Neurosurgery, Department of Neurosurgery, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Neuropathology, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Experimental Neurosurgery, Department of Neurosurgery, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Experimental Neurosurgery, Department of Neurosurgery, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, GermanyDivision for Stereotactic Neurosurgery, Department of Neurosurgery, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Experimental Neurosurgery, Department of Neurosurgery, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Experimental Neurosurgery, Department of Neurosurgery, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany<i>IDH</i>-wildtype glioblastoma (GBM) represents the most common malignant form of brain tumor and is still incurable despite comprehensive therapeutic efforts. Due to tumor location and patient condition, open surgical resection of recurrent GBM is not always feasible. In these cases, frame-based stereotactic biopsies represent a less invasive technique to obtain tissue samples for diagnostics. However, whether this material would also be sufficient to prepare tumor organoids (TOs) and perform drug screenings has not been addressed so far. In this study, we present our highly optimized workflow for generating standardized patient-derived GBM TOs from single-cell suspensions using limited biopsy-derived material. We highlight crucial steps within the procedure, such as reliable cell counting, viable cell recovery, enzymatic digestion, and the requirement of an extracellular matrix as a scaffold. Furthermore, we showcase the potential of personalized drug testing as a promising application of GBM TOs. In conclusion, we successfully developed a robust workflow that effectively utilizes the limited material derived from stereotactic biopsies to reproducibly form standardized TOs. Moreover, we demonstrate that biopsy-derived TOs represent a valuable tool for testing drug vulnerabilities in a personalized setting, which might be especially useful in the case of non-resectable GBM.https://www.mdpi.com/2073-4409/14/10/701glioblastomapatient-derived tumor organoidsstereotactic biopsyprecision medicine
spellingShingle Amélie Wöllner
Adrian Paul
Maddalena Arquilla
Junguo Cao
Catharina Lotsch
Gerhard Jungwirth
Lena Jassowicz
Andreas von Deimling
Andreas W. Unterberg
Sandro M. Krieg
Martin Jakobs
Rolf Warta
Christel Herold-Mende
Use of Tissue Specimens from Stereotactic Biopsies for Patient-Derived GBM Organoid-Based Drug Testing
Cells
glioblastoma
patient-derived tumor organoids
stereotactic biopsy
precision medicine
title Use of Tissue Specimens from Stereotactic Biopsies for Patient-Derived GBM Organoid-Based Drug Testing
title_full Use of Tissue Specimens from Stereotactic Biopsies for Patient-Derived GBM Organoid-Based Drug Testing
title_fullStr Use of Tissue Specimens from Stereotactic Biopsies for Patient-Derived GBM Organoid-Based Drug Testing
title_full_unstemmed Use of Tissue Specimens from Stereotactic Biopsies for Patient-Derived GBM Organoid-Based Drug Testing
title_short Use of Tissue Specimens from Stereotactic Biopsies for Patient-Derived GBM Organoid-Based Drug Testing
title_sort use of tissue specimens from stereotactic biopsies for patient derived gbm organoid based drug testing
topic glioblastoma
patient-derived tumor organoids
stereotactic biopsy
precision medicine
url https://www.mdpi.com/2073-4409/14/10/701
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