4 research outputs found
Are we ready to integrate 3D culture systems in acute myeloid leukemia and bone marrow microenvironment research?
No full textAcute myeloid leukemia (AML) is the most aggressive adult leukemia and results in a dismal 5-year survival rate of less than 30%. While research has primarily focused on identifying intrinsic mutations driving leukemogenesis, the role of the bone marrow microenvironment (BMME) in disease progression remains poorly understood. For this purpose, conventional 2D cultures inadequately replicate the complex BMME interactions crucial for the maintenance of normal hematopoiesis and leukemia pathogenesis. In recent years, 3D cultures or microphysiological systems (MPS), have emerged as promising tools for in vitro modeling of the human BMME. These approaches provide a promise for a more physiologically relevant platform for investigating the mechanistic underpinnings of AML interactions with BMME components, as well as exploring chemoresistance mechanisms and facilitating drug discovery efforts. This review discusses the considerations in biomaterials, biophysical, and biochemical factors to develop the BMME in vitro for AML studies, the state-of-the-art 3D models of the BMME, and the challenges and prospects of adopting MPS for AML research
DataSheet1_Bone Marrow Microenvironment-On-Chip for Culture of Functional Hematopoietic Stem Cells.PDF
No full textHematopoiesis takes place in the bone marrow and is supported by a complex cellular and molecular network in the bone marrow microenvironment. Commonly used models of the human bone marrow microenvironment include murine models and two-dimensional and three-dimensional tissue cultures. While these model systems have led to critical advances in the field, they fail to recapitulate many aspects of the human bone marrow. This has limited our understanding of human bone marrow pathophysiology and has led to deficiencies in therapy for many bone marrow pathologies such as bone marrow failure syndromes and leukemias. Therefore, we have developed a modular murine bone marrow microenvironment-on-chip using a commercially available microfluidic platform. This model includes a vascular channel separated from the bone marrow channel by a semi-porous membrane and incorporates critical components of the bone marrow microenvironment, including osteoblasts, endothelial cells, mesenchymal stem cells, and hematopoietic stem and progenitor cells. This system is capable of maintaining functional hematopoietic stem cells in vitro for at least 14 days at frequencies similar to what is found in the primary bone marrow. The modular nature of this system and its accessibility will allow for acceleration of our understanding of the bone marrow.</p
