Bone marrow niche-mimetics modulate HSPC function via integrin signaling

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 naive cell deformation compared to SN-cells indicating physical recognition of ECM material properties by focal adhesion. Integrin alpha IIb (CD41), alpha V (CD51) and beta 3 (CD61) were found to be induced. Signaling focal contacts via ITG beta 3 were identified to facilitate cell adhesion, migration and mediate ECM-physical cues to modulate HSPC function.