IGFBP3 deposited in the human umbilical cord mesenchymal stem cell-secreted extracellular matrix promotes bone formation.

摘要: The extracellular matrix (ECM) contains rich biological cues for cell recruitment, proliferationm, and even differentiation. osteoinductive potential of scaffolds could be enhanced through human bone marrow mesenchymal stem (hBMSC) directly depositing ECM on surface scaffolds. However, the role mechanism umbilical cord cells (hUCMSC)-secreted in formation remain unknown. We tested properties a hUCMSC-secreted construct (hUCMSC-ECM) large femur defect severe combined immunodeficiency (SCID) mouse model. hUCMSC-ECM improved colonization endogenous MSCs regeneration, similar to hUCMSC-seeded scaffold superior substrate. Besides, promigratory molecular expressions homing cells, including CCR2 TβRI. Furthermore, increased number migrated by nearly 3.3 ± 0.1-fold, relative As most abundant cytokine deposited hUCMSC-ECM, insulin-like growth factor binding protein 3 (IGFBP3) promoted hBMSC migration TβRI/II- CCR2-dependent mechanisms. integrating shRNA-mediated silencing Igfbp3 that down-regulated IGFBP3 expression approximately 60%, reduced hBMSCs 47%. In vivo, recruited 10-fold more initiate compared knock-down inhibited 60% MSC regeneration capacity. This research demonstrates is an important molecule therapeutic improving IGFBP3-dependent mechanism.