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Adv. Healthc. Mater., Feb 06 2024, | https://doi.org/10.1002/adhm.202304371 Brain-Decellularized ECM-Based 3D Myeloid Sarcoma Platform: Mimicking Adaptive Phenotypic Alterations in the Brain

Heejeong Yoon ¹, Joo H Kang ¹, Seung Woo Cho¹, Chun Gwon Park ^2,3, Dong-Wook Kim ^4,5, Tae-Eun Park ¹

¹Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.

²Department of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea.

³Department of Intelligent Precision Healthcare Convergence, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea.

⁴Department of Hematology, Hematology Center, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu, 11750, Republic of Korea.

⁵Leukemia Omics Research Institute, Eulji University, Uijeongbu, 11750, Republic of Korea.

CORRESPONDING AUTHORS : Dong-Wook Kim, Tae-Eun Park

Abstract

Leukemia circulates in the bloodstream and induces various symptoms and complications. Occasionally, these cells accumulate in non-marrow tissues, forming a tumor-like myeloid sarcoma (MS). When the blast-stage leukemia cells invade the brain parenchyma, intracranial MS occurs, leading to a challenging prognosis owing to the limited penetration of cytostatic drugs into the brain and the development of drug resistance. The scarcity of tissue samples from MS makes understanding the phenotypic changes occurring in leukemia cells within the brain environment challenging, thereby hindering development of effective treatment strategies for intracranial MS. This study presents a novel 3D in vitro model mimicking intracranial MS, employing a hydrogel scaffold derived from the brain-decellularized extracellular matrix in which suspended leukemia cells are embedded, simulating the formation of tumor masses in the brain parenchyma. This model reveals marked phenotypic changes in leukemia cells, including altered survival, proliferation, differentiation, and cell cycle regulation. Notably, proportion of dormant leukemia stem cells increases and expression of multidrug resistance genes is upregulated, leading to imatinib resistance, mirroring the pathological features of in vivo MS tissue. Furthermore, suppression of ferroptosis is identified as an important characteristic of intracranial MS, providing valuable insights for the development of targeted therapeutic strategies.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-21)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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