Scheme of the proposed model. At steady-state conditions, HSPCs reside in proximity to “niche” supportive Nestin⁺ MSCs. FGF-2 is expressed locally in low levels, allowing low-key steady-state maintenance of HSPCs. CXCL12 is expressed at high levels, keeping HSPCs in a quiescent state. After FGF-2 treatment, a dual increase in the Nestin⁺ MSC and the HSPC pool size occurs. Stromal CXCL12 levels are reduced via mir-31 up-regulation, allowing HSPCs to exit from their quiescent state and begin cycling. Stromal SCF levels are up-regulated, activating c-Kit, which is highly expressed by FGF-2–stimulated HSPCs. Activated c-Kit expands the pool of HSPCs and increases LTR-HSC capacity by decreasing intracellular ROS levels and activating stem cell–maintaining factors such as STAT5.