Space constraints govern fate of hematopoietic stem and progenitor cells in vitro

被引:20
作者
Mueller, Eike [1 ]
Grinenko, Tatyana [2 ]
Pompe, Tilo [1 ,3 ]
Waskow, Claudia [2 ]
Werner, Carsten [1 ]
机构
[1] Leibniz Inst Polymer Res Dresden, Max Bergmann Ctr Biomat, D-01069 Dresden, Germany
[2] Tech Univ Dresden, Inst Immunol, Regenerat Hematopoiesis & Anim Models Hematopoies, D-01307 Dresden, Germany
[3] Univ Leipzig, Inst Biochem, D-04103 Leipzig, Germany
关键词
ECM; In vivo test; Microstructure; Stem cell; BONE-MARROW; LONG-TERM; STEM/PROGENITOR CELLS; ADHESION MOLECULES; ARTIFICIAL NICHES; CD34(+) CELLS; ENGRAFTMENT; EXPRESSION; CYTOKINES; MOBILIZATION;
D O I
10.1016/j.biomaterials.2015.02.095
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Deciphering exogenous cues that determine stem cell fate decisions is a persisting challenge of cell biology and bioengineering. In an effort to unravel the role of spatial constraints in the cell-instructive characteristics of bone marrow microenvironments, murine hematopoietic stem and progenitor cells (HSPC) were exposed to fibronectin-coated microcavities in vitro. Microcavity sizes were chosen to allow for the inclusion of either individual or multiple cells. Repopulation experiments using lethally irradiated mice showed that the maintenance of functional HSPC in culture critically depends on cavity dimensions. Short-term repopulating hematopoietic stem cells (ST-HSC) were found to be best supported within single-cell sized compartments while long-term repopulating HSC (LT-HSC) were maintained within both cavity sizes. In sum, the reported data reveal spatial restriction to be a simple but powerful means for directing HSPC fate ex vivo. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:709 / 715
页数:7
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