Microenvironment matters: In vitro 3D bone marrow niches differentially modulate survival, phenotype and drug responses of acute myeloid leukemia (AML) cells.

Autor: Cheung HL; School of Biomedical Science, Institute of Tissue Engineering and Regenerative Medicine, And Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pok Fu Lam Road, Hong Kong SAR, China; Advanced Biomedical Instrumentation Centre, Hong Kong Science Park, Shatin, New Territories, Hong Kong SAR, China., Wong YH; School of Biomedical Science, Institute of Tissue Engineering and Regenerative Medicine, And Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pok Fu Lam Road, Hong Kong SAR, China; Advanced Biomedical Instrumentation Centre, Hong Kong Science Park, Shatin, New Territories, Hong Kong SAR, China., Li YY; School of Biomedical Science, Institute of Tissue Engineering and Regenerative Medicine, And Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pok Fu Lam Road, Hong Kong SAR, China., Yang X; Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pok Fu Lam Road, Hong Kong SAR, China., Ko LH; School of Biomedical Science, Institute of Tissue Engineering and Regenerative Medicine, And Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China., Tan Kabigting JE; Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pok Fu Lam Road, Hong Kong SAR, China., Chan KC; Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Leung AYH; Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Chan BP; School of Biomedical Science, Institute of Tissue Engineering and Regenerative Medicine, And Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pok Fu Lam Road, Hong Kong SAR, China; Advanced Biomedical Instrumentation Centre, Hong Kong Science Park, Shatin, New Territories, Hong Kong SAR, China. Electronic address: bpchan@cuhk.edu.hk.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2025 Jan; Vol. 312, pp. 122719. Date of Electronic Publication: 2024 Jul 27.
DOI: 10.1016/j.biomaterials.2024.122719
Abstrakt: Acute myeloid leukemia (AML) is a deadly form of leukemia with ineffective traditional treatment and frequent chemoresistance-associated relapse. Personalized drug screening holds promise in identifying optimal regimen, nevertheless, primary AML cells undergo spontaneous apoptosis during cultures, invalidating the drug screening results. Here, we reconstitute a 3D osteogenic niche (3DON) mimicking that in bone marrow to support primary AML cell survival and phenotype maintenance in cultures. Specifically, 3DON derived from osteogenically differentiated mesenchymal stem cells (MSC) from healthy and AML donors are co-cultured with primary AML cells. The AML cells under the AML_3DON niche showed enhanced viability, reduced apoptosis and maintained CD33 + CD34 - phenotype, associating with elevated secretion of anti-apoptotic cytokines in the AML_3DON niche. Moreover, AML cells under the AML_3DON niche exhibited low sensitivity to two FDA-approved chemotherapeutic drugs, further suggesting the physiological resemblance of the AML_3DON niche. Most interestingly, AML cells co-cultured with the healthy_3DON niche are highly sensitive to the same sample drugs. This study demonstrates the differential responses of AML cells towards leukemic and healthy bone marrow niches, suggesting the impact of native cancer cell niche in drug screening, and the potential of re-engineering healthy bone marrow niche in AML patients as chemotherapeutic adjuvants overcoming chemoresistance, respectively.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The authors (Barbara Pui Chan, Hoi Lam Cheung, Anskar Yu Hung Leung and Jessica Evangeline Tan Kabigting) hold a patent associated with the current work.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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