Brain-Decellularized ECM-Based 3D Myeloid Sarcoma Platform: Mimicking Adaptive Phenotypic Alterations in the Brain.
Heejeong YoonJoo H KangSeung Woo ChoChun Gwon ParkDong-Wook KimTae-Eun ParkPublished in: Advanced healthcare materials (2024)
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.
Keyphrases
- induced apoptosis
- mass spectrometry
- multiple sclerosis
- bone marrow
- acute myeloid leukemia
- extracellular matrix
- resting state
- white matter
- ms ms
- cell cycle arrest
- stem cells
- cell cycle
- functional connectivity
- signaling pathway
- endoplasmic reticulum stress
- gene expression
- poor prognosis
- immune response
- cerebral ischemia
- drug delivery
- oxidative stress
- physical activity
- dendritic cells
- high throughput
- multidrug resistant
- mesenchymal stem cells
- gram negative
- subarachnoid hemorrhage
- cell therapy
- optical coherence tomography