Bone Marrow Microenvironment-On-Chip for Culture of Functional Hematopoietic Stem Cells

被引:17
作者
Sharipol, Azmeer [1 ,2 ]
Lesch, Maggie L. [3 ]
Soto, Celia A. [2 ,4 ]
Frisch, Benjamin J. [1 ,2 ,4 ,5 ]
机构
[1] Univ Rochester, Dept Biomed Engn, Rochester, NY 14627 USA
[2] Univ Rochester, Med Ctr, Ctr Musculoskeletal Res, Rochester, NY 14627 USA
[3] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY USA
[4] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14627 USA
[5] Univ Rochester, Med Ctr, Wilmot Canc Inst, Rochester, NY 14627 USA
关键词
bone marrow; hematopoietic stem cell; bone marrow microenvironment; bone marrow on a chip; tissue engineering; 3D chip; osteoblast; mesenchymal stem cell; LEUKEMIA; INHIBITION; MODEL;
D O I
10.3389/fbioe.2022.855777
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Hematopoiesis 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.
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页数:15
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