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Adv. Healthc. Mater., Mar 12 2025, | https://doi.org/10.1002/adhm.202404821
A Neuroimmune-Oncology Microphysiological Analysis Platform (NEO-MAP) for Evaluating Astrocytic Scar Formation and Microgliosis in Glioblastoma Microenvironment
Yen N. Diep 1,2,3, Hee Jung Park 4, Xiaohui Zhu 1,2, Jin Ho Nam 4, Jin-Kyoung Shim 5,6, Jong Hee Chang 5, Dang Du Nguyen 1,2,3, Inki Kim 1,2,3, Dong-Gyu Jo 1,7,8,9, Luke P. Lee 1,2,10,11, Mijin Yun 4, Hansang Cho 1,2,3
1Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
2Department of Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
3Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
4Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
5Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
6Brain Tumor Translational Research Laboratory, Severance Biomedical Research Institute, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
7School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
8Biomedical Institute for Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
9Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, 06351, Republic of Korea.
10Harvard Medical School, Division of Engineering in Medicine and Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
11Department of Bioengineering, Department of Electrical Engineering and Computer Science, University of California, Berkeley, CA, 94720, USA.
Y.N.D and H.J.P. contributed equally to this work.
Corresponding Authors: Luke P. Lee, Mijin Yun, Hansang Cho
1Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
2Department of Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
3Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
4Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
5Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
6Brain Tumor Translational Research Laboratory, Severance Biomedical Research Institute, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
7School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
8Biomedical Institute for Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
9Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, 06351, Republic of Korea.
10Harvard Medical School, Division of Engineering in Medicine and Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
11Department of Bioengineering, Department of Electrical Engineering and Computer Science, University of California, Berkeley, CA, 94720, USA.
Y.N.D and H.J.P. contributed equally to this work.
Corresponding Authors: Luke P. Lee, Mijin Yun, Hansang Cho
Abstract
Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor, characterized by its heterogeneity in cellular components, including reactive astrocytes and microglia. Since neuroimmune responses like astrogliosis and microgliosis gain recognition as vital factors in brain tumor progression, there is a growing need for clinically relevant models that assess the interactions between astrocytes, microglia, and GBM. Here, a NEuroimmune-Oncology Microphysiological Analysis Platform (NEO-MAP) is presented as a "new map" to observe astrocytic scar formation and microgliosis in response to GBM. NEO-MAP based on pathophysiological principles is designed to replicate the GBM-glia interactions, multi-phenotypic microglia activities, scar-forming astrocytes with chondroitin sulfate proteoglycans (CSPGs) in the extracellular matrix, and the biophysical characteristics of the astrocytic scar barrier. The NEO-MAP reveals that inhibiting mTORC2 in GBM promotes the proinflammatory transformation of astrocytes and enhanced astrocytic scar formation. Astrocytes that form scars prompted microglia to change from the M2 to M1 phenotype, enhancing chemotherapy sensitivity. Tissues from GBM patients show a significant correlation between reduced mTORC2 activity and increased astrogliosis, alongside a decrease in M2-polarized microgliosis, aligning with the NEO-MAP findings. Overall, the NEO-MAP is foreseen as a clinically significant tool for exploring tumor-glia interactions, opening avenues for drug development aimed at the tumor microenvironment.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-14)
- 국내(교신)+국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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