Hematopoietic stem and progenitor cells in adhesive microcavities

被引:47
作者
Kurth, Ina [1 ]
Franke, Katja [1 ]
Pompe, Tilo [1 ]
Bornhaeuser, Martin [2 ,3 ]
Werner, Carsten [1 ,3 ]
机构
[1] Max Bergmann Ctr Biomat, Leibniz Inst Polymer Res, D-01069 Dresden, Germany
[2] Univ Klinikum Carl Gustav Carus, Med Klin & Poliklin 1, D-01307 Dresden, Germany
[3] Ctr Regenerat Therapies Dresden, D-01307 Dresden, Germany
关键词
EX-VIVO EXPANSION; CORD BLOOD-CELLS; BONE-MARROW; FIBRONECTIN; PROLIFERATION; NICHES; MICROENVIRONMENT; DIFFERENTIATION; EXPRESSION; RECEPTORS;
D O I
10.1039/b903711j
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The homeostasis of hematopoietic stern and progenitor cells (HSC) in the bone marrow is regulated by a complex interplay of exogenous signals, including extracellular matrix (ECM) molecules, cell-cell contacts, and cytokines. To investigate the influence of spatial restriction and adhesive interactions on HSC fate decisions, we prepared a set of fibronectin-coated micrometer-sized cavities. Analysis of human CD133 + HSCs isolated after culture on these surfaces revealed that proliferation and differentiation is decreased when HSCs are supported by substrates with small microcavities. Single cell analysis of adherent cells also revealed decreased DNA synthesis and higher levels of HSC marker expression inside the smaller cavities. Increasing the cytokine concentration highlighted the tight balance of adhesion related signals and soluble cues acting on HSC fate decisions. Our results suggest that confining human HSCs in ECM-coated microcavities is a possible method to maintain these cells in a quiescent and immature state, an important advantage for several HSC applications.
引用
收藏
页码:427 / 434
页数:8
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