Deciphering Human Glioblastoma Invasion Using a Developmental Mature Rat Brain Organoid Model

Wenjing Zhou; Frits A. Thorsen; Konrad Grützmann; Boris Mihaljevic; Barbara van Loon; Jubayer A. Hossain; Anna Golebiewska; Simone Niclou; Magnar Bjørås; Saverio Tardito; Justin Vareecal Joesph; Elena Martinez-Garcia; Taral R. Lunavat; Halala Sdik Saed; Marzieh Bahador; Minghzi Han; Carina Fabian; Hrvoje Miletic; Xingang Li; Jian Wang; Gunnar Dittmar; Olivier Keunen; Katharina Sarnow; Barbara Klink; Rolf Bjerkvig; Georgia Kanli; Petr Nazarov; Stephanie G. Schwab; Johannes Meiser; Christian Jäger; Jakub Mieczkowski

doi:10.2139/ssrn.4248356

Deciphering Human Glioblastoma Invasion Using a Developmental Mature Rat Brain Organoid Model

Wenjing Zhou, Frits A. Thorsen, Konrad Grützmann, Boris Mihaljevic, Barbara van Loon, Jubayer A. Hossain, Anna Golebiewska, Simone Niclou, Magnar Bjørås, Saverio Tardito, Justin Vareecal Joesph, Elena Martinez-Garcia, Taral R. Lunavat, Halala Sdik Saed, Marzieh Bahador, Minghzi Han, Carina Fabian, Hrvoje Miletic, Xingang Li, Jian WangGunnar Dittmar, Olivier Keunen, Katharina Sarnow, Barbara Klink, Rolf Bjerkvig, Georgia Kanli, Petr Nazarov, Stephanie G. Schwab, Johannes Meiser, Christian Jäger, Jakub Mieczkowski

Research output: Working paper › Preprint

Abstract

To model neurological diseases using brain organoids (BOs), there is a need for the development of terminally differentiated structures that reflect the structural and cellular complexity of mature brain tissue. Here we describe the developmental path of rat brain organoids (rBOs) into terminally differentiated brain structures. These organoids were compared to BOs derived from induced human pluripotent stem cells (iPSC) at the transcriptomic, proteomic and metabolomic level, showing that the rBOs present a higher degree of brain maturation. We further show that the rBOs can be used as an ex vivo avatar co-culture system to decipher important glioblastoma invasion parameters such as invasive cellular heterogeneity between patient-derived glioblastoma cells where key invasion parameters such as speed of single cell invasion and replacement of brain tissue by tumor cells can be measured and quantified in real-time. Finally, we show how this model can be used to assess therapeutic interventions, among others, directed toward neuro-gliomal α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor communication.

Original language	English
DOIs	https://doi.org/10.2139/ssrn.4248356
Publication status	Published - 15 Nov 2022

Publication series

Name	DEVELOPMENTAL-CELL-D-22-00801

Keywords

Brain organoids
glioblastoma
invasion
inhibition

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Zhou, W., Thorsen, F. A., Grützmann, K., Mihaljevic, B., van Loon, B., Hossain, J. A., Golebiewska, A., Niclou, S., Bjørås, M., Tardito, S., Joesph, J. V., Martinez-Garcia, E., Lunavat, T. R., Saed, H. S., Bahador, M., Han, M., Fabian, C., Miletic, H., Li, X., ... Mieczkowski, J. (2022). Deciphering Human Glioblastoma Invasion Using a Developmental Mature Rat Brain Organoid Model. (DEVELOPMENTAL-CELL-D-22-00801). https://doi.org/10.2139/ssrn.4248356

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title = "Deciphering Human Glioblastoma Invasion Using a Developmental Mature Rat Brain Organoid Model",

abstract = "To model neurological diseases using brain organoids (BOs), there is a need for the development of terminally differentiated structures that reflect the structural and cellular complexity of mature brain tissue. Here we describe the developmental path of rat brain organoids (rBOs) into terminally differentiated brain structures. These organoids were compared to BOs derived from induced human pluripotent stem cells (iPSC) at the transcriptomic, proteomic and metabolomic level, showing that the rBOs present a higher degree of brain maturation. We further show that the rBOs can be used as an ex vivo avatar co-culture system to decipher important glioblastoma invasion parameters such as invasive cellular heterogeneity between patient-derived glioblastoma cells where key invasion parameters such as speed of single cell invasion and replacement of brain tissue by tumor cells can be measured and quantified in real-time. Finally, we show how this model can be used to assess therapeutic interventions, among others, directed toward neuro-gliomal α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor communication.",

keywords = "Brain organoids, glioblastoma, invasion, inhibition",

author = "Wenjing Zhou and Thorsen, {Frits A.} and Konrad Gr{\"u}tzmann and Boris Mihaljevic and {van Loon}, Barbara and Hossain, {Jubayer A.} and Anna Golebiewska and Simone Niclou and Magnar Bj{\o}r{\aa}s and Saverio Tardito and Joesph, {Justin Vareecal} and Elena Martinez-Garcia and Lunavat, {Taral R.} and Saed, {Halala Sdik} and Marzieh Bahador and Minghzi Han and Carina Fabian and Hrvoje Miletic and Xingang Li and Jian Wang and Gunnar Dittmar and Olivier Keunen and Katharina Sarnow and Barbara Klink and Rolf Bjerkvig and Georgia Kanli and Petr Nazarov and Schwab, {Stephanie G.} and Johannes Meiser and Christian J{\"a}ger and Jakub Mieczkowski",

year = "2022",

month = nov,

day = "15",

doi = "10.2139/ssrn.4248356",

language = "English",

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Zhou, W, Thorsen, FA, Grützmann, K, Mihaljevic, B, van Loon, B, Hossain, JA, Golebiewska, A, Niclou, S, Bjørås, M, Tardito, S, Joesph, JV, Martinez-Garcia, E, Lunavat, TR, Saed, HS, Bahador, M, Han, M, Fabian, C, Miletic, H, Li, X, Wang, J, Dittmar, G , Keunen, O, Sarnow, K, Klink, B, Bjerkvig, R, Kanli, G , Nazarov, P, Schwab, SG, Meiser, J, Jäger, C & Mieczkowski, J 2022 'Deciphering Human Glioblastoma Invasion Using a Developmental Mature Rat Brain Organoid Model' DEVELOPMENTAL-CELL-D-22-00801. https://doi.org/10.2139/ssrn.4248356

TY - UNPB

T1 - Deciphering Human Glioblastoma Invasion Using a Developmental Mature Rat Brain Organoid Model

AU - Zhou, Wenjing

AU - Thorsen, Frits A.

AU - Grützmann, Konrad

AU - Mihaljevic, Boris

AU - van Loon, Barbara

AU - Hossain, Jubayer A.

AU - Golebiewska, Anna

AU - Niclou, Simone

AU - Bjørås, Magnar

AU - Tardito, Saverio

AU - Joesph, Justin Vareecal

AU - Martinez-Garcia, Elena

AU - Lunavat, Taral R.

AU - Saed, Halala Sdik

AU - Bahador, Marzieh

AU - Han, Minghzi

AU - Fabian, Carina

AU - Miletic, Hrvoje

AU - Li, Xingang

AU - Wang, Jian

AU - Dittmar, Gunnar

AU - Keunen, Olivier

AU - Sarnow, Katharina

AU - Klink, Barbara

AU - Bjerkvig, Rolf

AU - Kanli, Georgia

AU - Nazarov, Petr

AU - Schwab, Stephanie G.

AU - Meiser, Johannes

AU - Jäger, Christian

AU - Mieczkowski, Jakub

PY - 2022/11/15

Y1 - 2022/11/15

N2 - To model neurological diseases using brain organoids (BOs), there is a need for the development of terminally differentiated structures that reflect the structural and cellular complexity of mature brain tissue. Here we describe the developmental path of rat brain organoids (rBOs) into terminally differentiated brain structures. These organoids were compared to BOs derived from induced human pluripotent stem cells (iPSC) at the transcriptomic, proteomic and metabolomic level, showing that the rBOs present a higher degree of brain maturation. We further show that the rBOs can be used as an ex vivo avatar co-culture system to decipher important glioblastoma invasion parameters such as invasive cellular heterogeneity between patient-derived glioblastoma cells where key invasion parameters such as speed of single cell invasion and replacement of brain tissue by tumor cells can be measured and quantified in real-time. Finally, we show how this model can be used to assess therapeutic interventions, among others, directed toward neuro-gliomal α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor communication.

AB - To model neurological diseases using brain organoids (BOs), there is a need for the development of terminally differentiated structures that reflect the structural and cellular complexity of mature brain tissue. Here we describe the developmental path of rat brain organoids (rBOs) into terminally differentiated brain structures. These organoids were compared to BOs derived from induced human pluripotent stem cells (iPSC) at the transcriptomic, proteomic and metabolomic level, showing that the rBOs present a higher degree of brain maturation. We further show that the rBOs can be used as an ex vivo avatar co-culture system to decipher important glioblastoma invasion parameters such as invasive cellular heterogeneity between patient-derived glioblastoma cells where key invasion parameters such as speed of single cell invasion and replacement of brain tissue by tumor cells can be measured and quantified in real-time. Finally, we show how this model can be used to assess therapeutic interventions, among others, directed toward neuro-gliomal α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor communication.

KW - Brain organoids

KW - glioblastoma

KW - invasion

KW - inhibition

U2 - 10.2139/ssrn.4248356

DO - 10.2139/ssrn.4248356

M3 - Preprint

T3 - DEVELOPMENTAL-CELL-D-22-00801

BT - Deciphering Human Glioblastoma Invasion Using a Developmental Mature Rat Brain Organoid Model

ER -

Deciphering Human Glioblastoma Invasion Using a Developmental Mature Rat Brain Organoid Model

Abstract

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