Combined influence of biophysical and biochemical cues on maintenance and proliferation of hematopoietic stem cells

被引：45
作者：
Gvaramia, David [1 ]
Mueller, Eike [2 ]
Mueller, Katrin [4 ]
Atallah, Passant [1 ]
Tsurkan, Mikhail [1 ]
Freudenberg, Uwe [1 ]
Bornhaeuser, Martin [4 ]
Werner, Carsten [1 ,3 ]
机构：
[1] Max Bergmann Ctr Biomat, Leibniz Inst Polymer Res Dresden, D-01069 Dresden, Germany
[2] Swiss Fed Labs Mat Sci & Technol, Empa, Lab Biointerfaces, CH-9014 St Gallen, Switzerland
[3] Tech Univ Dresden, Ctr Regenerat Therapies Dresden, D-01307 Dresden, Germany
[4] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Med Clin 1, Dresden, Germany
来源：
BIOMATERIALS | 2017年 / 138卷
关键词：
Hematopoietic stem cell; 3D microenvironment; Substrate stiffness; Heparin; Cell fate; PROGENITOR CELLS; SUBSTRATE ELASTICITY; IN-VITRO; 3-DIMENSIONAL HYDROGELS; FATE; DIFFERENTIATION; EXPANSION; NICHES; MICROENVIRONMENTS; BIOMATERIALS;
D O I：
10.1016/j.biomaterials.2017.05.023
中图分类号：
R318 [生物医学工程];
学科分类号：
0831 ;
摘要：
Homeostasis of hematopoietic stem and progenitor cells (HSPC) is controlled by a combination of biochemical and biophysical environmental cues in the bone marrow (BM) niche, where a tight balance of quiescence and proliferation of HSPC is maintained. Specifically, alongside soluble factors and extracellular matrix (ECM) proteins, spatial confinement and ECM stiffness have been recognized to be critical for regulation of HSPC fate. Here we employ a modular, glycosaminoglycan (GAG)-based biohybrid hydrogel system to balance proliferation of human HSPC and maintenance of quiescent hematopoietic stem cells (HSC) through simultaneous regulation of exogenous biochemical and biophysical cues. Our results demonstrate that HSPC respond to increased spatial confinement with lowered proliferation and cell cycling, which results in higher frequency of quiescent LTC-IC (long-term culture initiating cells), while GAG-rich 3D environments further support maintenance of the cells. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码：108 / 117
页数：10
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