Development of a 3D ex vivo model of brain-leukemia interaction to study the role of activin A in the central nervous system microenvironment

被引：0

作者：

Erica Dander ^{[1
]}

Francesca Pischiutta ^{[2
]}

Noemi Di Marzo ^{[1
]}

Rosaria Pascente ^{[2
]}

Nicolò Panini ^{[3
]}

Alessandra Fallati ^{[5
]}

Andrea Biondi ^{[1
]}

Elisa R. Zanier ^{[1
]}

Giovanna D’Amico ^{[4
]}

机构：

[1] Fondazione IRCCS San Gerardo dei Tintori,Tettamanti Center

[2] Istituto di Ricerche Farmacologiche Mario Negri IRCCS,Departement of Acute Brain and Cardiovascular Injury

[3] Istituto di Ricerche Farmacologiche Mario Negri IRCCS,Departement of Oncology

[4] Fondazione IRCCS San Gerardo dei Tintori,Pediatrics

[5] Human Technopole,undefined

来源：

Scientific Reports | / 15卷 / 1期

关键词：

Acute lymphoblastic leukemia; Leukemia microenvironment; Organotypic brain slices; 3-dimensional model; Activin A;

D O I：

10.1038/s41598-025-03877-w

中图分类号：

学科分类号：

摘要：

B-cell type acute lymphoblastic leukemia (B-ALL) is the most common type of childhood malignancy. Although the survival rate nowadays exceeds 90%, central nervous system (CNS) involvement is associated with a poor outcome. Experimental models are needed to study the interaction between leukemia cells and the brain microenvironment to unravel new targets for drug intervention. We developed a novel three-dimensional (3D) ex vivo model utilizing murine organotypic cortical brain slices microinjected with human B-ALL cells, serving as a platform for investigating the influence of Activin A, a pro-leukemic factor, on leukemia invasion into the CNS. After injection, B-ALL cells exponentially increased in the cortical slices, promoting tissue mortality and an anti-inflammatory microenvironment phenotype, as demonstrated by morphological and gene expression alterations in microglia and astrocytes. Of note, Activin A pretreatment increased leukemia proliferation and exacerbated the effects on the microenvironment. Overall, our model presents an ideal platform for investigating the cross-talk between tumors and the brain microenvironment and the influence of disease-modifying factors. Moreover, it could facilitate drug screening across a spectrum of CNS cancers, meanwhile reducing animal usage.

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