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Three-Dimensional Microfluidic Tri-Culture Model of the Bone Marrow Microenvironment for Study of Acute Lymphoblastic Leukemia

Bruce, Allison ; Evans, Rebecca ; Mezan, Ryan ; Shi, Lin ; Moses, Blake S ; Martin, Karen H ; Gibson, Laura F ; Yang, Yong Zhao, Feng

PloS one, 2015-10, Vol.10 (10), p.e0140506-e0140506 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Three-Dimensional Microfluidic Tri-Culture Model of the Bone Marrow Microenvironment for Study of Acute Lymphoblastic Leukemia
Autor: Bruce, Allison ; Evans, Rebecca ; Mezan, Ryan ; Shi, Lin ; Moses, Blake S ; Martin, Karen H ; Gibson, Laura F ; Yang, Yong
Zhao, Feng
Assuntos: Acute lymphatic leukemia ; Acute lymphoblastic leukemia ; Acute lymphocytic leukemia ; Biocompatibility ; Biomedical materials ; Bone marrow ; Bone Marrow - pathology ; Bone Marrow Cells - cytology ; Cancer ; Cancer therapies ; Care and treatment ; Cell Communication - physiology ; Cell culture ; Cell Culture Techniques - methods ; Cell interactions ; Cell Line, Tumor ; Cell Survival ; Chemical engineering ; Chemotherapy ; Coculture Techniques - methods ; Collagen ; Cytarabine ; Diagnosis ; Drug resistance ; Extracellular matrix ; Fibroblasts ; Flow velocity ; Gene expression ; Genotype & phenotype ; Health aspects ; Humans ; In vivo methods and tests ; Leukemia ; Lymphatic leukemia ; Mesenchymal Stromal Cells - cytology ; Metastasis ; Microenvironments ; Microfluidics ; Microfluidics - instrumentation ; Microfluidics - methods ; Morphology ; Neurosciences ; Osteoblasts ; Osteoblasts - cytology ; Phenotypes ; Plastics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Risk factors ; Shear stress ; Stability ; Static models ; Stiffness ; Stromal cells ; Substrates ; Three dimensional models ; Tumor cells ; Tumor Microenvironment ; Tumors ; Two dimensional models
É parte de: PloS one, 2015-10, Vol.10 (10), p.e0140506-e0140506
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Conceived and designed the experiments: YY LFG. Performed the experiments: AB RE LS BSM. Analyzed the data: AB RE RM KHM YY. Contributed reagents/materials/analysis tools: KHM LFG YY. Wrote the paper: YY LFG.
Competing Interests: The authors have declared that no competing interests exist.
Descrição: Acute lymphoblastic leukemia (ALL) initiates and progresses in the bone marrow, and as such, the marrow microenvironment is a critical regulatory component in development of this cancer. However, ALL studies were conducted mainly on flat plastic substrates, which do not recapitulate the characteristics of marrow microenvironments. To study ALL in a model of in vivo relevance, we have engineered a 3-D microfluidic cell culture platform. Biologically relevant populations of primary human bone marrow stromal cells, osteoblasts and human leukemic cells representative of an aggressive phenotype were encapsulated in 3-D collagen matrix as the minimal constituents and cultured in a microfluidic platform. The matrix stiffness and fluidic shear stress were controlled in a physiological range. The 3-D microfluidic as well as 3-D static models demonstrated coordinated cell-cell interactions between these cell types compared to the compaction of the 2-D static model. Tumor cell viability in response to an antimetabolite chemotherapeutic agent, cytarabine in tumor cells alone and tri-culture models for 2-D static, 3-D static and 3-D microfluidic models were compared. The present study showed decreased chemotherapeutic drug sensitivity of leukemic cells in 3-D tri-culture models from the 2-D models. The results indicate that the bone marrow microenvironment plays a protective role in tumor cell survival during drug treatment. The engineered 3-D microfluidic tri-culture model enables systematic investigation of effects of cell-cell and cell-matrix interactions on cancer progression and therapeutic intervention in a controllable manner, thus improving our limited comprehension of the role of microenvironmental signals in cancer biology.
Editor: United States: Public Library of Science
Idioma: Inglês

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Three-Dimensional Microfluidic Tri-Culture Model of the Bone Marrow Microenvironment for Study of Acute Lymphoblastic Leukemia

Bruce, Allison ; Evans, Rebecca ; Mezan, Ryan ; Shi, Lin ; Moses, Blake S ; Martin, Karen H ; Gibson, Laura F ; Yang, Yong Zhao, Feng

United States: Public Library of Science

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