骨髓龛模拟物通过整合素信号调节 HSPC 功能。

Bone marrow niche-mimetics modulate HSPC function via integrin signaling.

机构信息

Medical Clinic I, University Hospital Carl Gustav Carus, Dresden, Saxony, 01307, Germany.

Biotechnology Center, Technische Universität Dresden, Dresden, Saxony, 01307, Germany.

出版信息

Sci Rep. 2017 May 31;7(1):2549. doi: 10.1038/s41598-017-02352-5.

The bone marrow (BM) microenvironment provides critical physical cues for hematopoietic stem and progenitor cell (HSPC) maintenance and fate decision mediated by cell-matrix interactions. However, the mechanisms underlying matrix communication and signal transduction are less well understood. Contrary, stem cell culture is mainly facilitated in suspension cultures. Here, we used bone marrow-mimetic decellularized extracellular matrix (ECM) scaffolds derived from mesenchymal stromal cells (MSCs) to study HSPC-ECM interaction. Seeding freshly isolated HSPCs adherent (AT) and non-adherent (SN) cells were found. We detected enhanced expansion and active migration of AT-cells mediated by ECM incorporated stromal derived factor one. Probing cell mechanics, AT-cells displayed naïve cell deformation compared to SN-cells indicating physical recognition of ECM material properties by focal adhesion. Integrin αIIb (CD41), αV (CD51) and β3 (CD61) were found to be induced. Signaling focal contacts via ITGβ3 were identified to facilitate cell adhesion, migration and mediate ECM-physical cues to modulate HSPC function.

骨髓（BM）微环境为造血干细胞和祖细胞（HSPC）的维持和由细胞-基质相互作用介导的命运决定提供了关键的物理线索。然而，基质通讯和信号转导的机制还不太清楚。相反，干细胞培养主要在悬浮培养中进行。在这里，我们使用源自间充质基质细胞（MSC）的骨髓模拟脱细胞细胞外基质（ECM）支架来研究 HSPC-ECM 相互作用。发现了新分离的 HSPCs 贴壁（AT）和非贴壁（SN）细胞的接种。我们检测到，基质衍生的因子 1 介导的 ECM 可增强 AT 细胞的扩增和活性迁移。探测细胞力学，与 SN 细胞相比，AT 细胞显示出幼稚细胞的变形，表明细胞对 ECM 材料特性的物理识别通过粘着斑。发现整合素αIIb（CD41）、αV（CD51）和β3（CD61）被诱导。通过 ITGβ3 鉴定信号转导的粘着斑以促进细胞黏附、迁移，并介导 ECM 物理线索调节 HSPC 功能。