Considerable interest surrounds the use of stem/progenitor cells (SCs) in tissue regeneration and repair. A variety of potential therapeutic cell types have been identified, including adult bone marrow (BM)-derived haematopoietic (HSC) and mesenchymal stem cells (MSC). Experimental studies suggest that HSCs and MSCs are able to alleviate inflammation and subsequently contribute to tissue repair. Local recruitment of injected SCs by the microcirculation of injured tissue is a likely prerequisite for repair. Limited recruitment of SCs subsequent to systemic infusion has been partly used to explain the poor clinical success of cellular therapy. The molecular adhesive mechanisms that underpin SC recruitment and retention in injured tissue remain poorly understood. Understanding these mechanisms may allow identification of strategies that can enhance SC recruitment and may improve the efficacy of SC-based therapies. HSCs express a variety of surface adhesion molecules (e.g. CD49d, CD18, CD44) that are important in mediating their recruitment to injured tissues. Our intravital microscopy studies, conducted on different murine organs, demonstrate tissue-specific recruitment of HSCs to the injured microvasculature. For instance, recruitment of HSCs in ischemically injured liver is dependent on the integrin sub-unit CD49d, while recruitment of HSCs in ischemically injured gut is dependent on the integrin sub-unit CD18. Additionally, a role for the non-integrin glycoprotein CD44 appears critical in mediating HSC recruitment to injured kidney. Since these adhesion molecules are essential for stem-endothelial cell interactions, modification of their surface expression, affinity for endothelial counterligands or avidity (clustering) may facilitate or impede recruitment of HSCs into specific tissues. In addition to direct manipulation of adhesion molecules, chemokine pre-treatment strategies have promise in enhancing HSC recruitment to injured tissues. HSC pre-treatment with chemokines such as CXCL12 (SDF-1α) or KC (murine functional IL-8 homologue) significantly enhances their recruitment into the microvasculature of the ischemically injured intestine. Pre-treatment of HSCs with either CXCL12 or the reactive oxygen species, hydrogen peroxide (H2O2), can increase cell adhesion in the ischemically injured intestine. Crucially, these factors are released into the local microenvironment following ischemic tissue injury. Pre-treatment strategies may enhance adhesion via a number of mechanisms, including enhanced integrin clustering. Indeed, we have demonstrated that our HSC pre-treatment strategies are able to enhance surface integrin clustering. For instance, H2O2 (100μM; 1hr) significantly increases surface clustering of integrins CD18 and CD49d without affecting HSC viability or function (still capable of differentiation into mature hematopoietic cells). Interestingly, pre-treatment strategies may also modify SC kinetics through non-adhesion molecule related mechanisms. For instance, we have data to show that CXCL12 pre-treatment increases HSC deformability, as demonstrated using a micropipette aspiration method. This has important clinical implications as non-specific entrapment is considered a major obstacle for systemic SC delivery. Non-specific entrapment may reduce the pool of circulating transplanted SCs available for recruitment. An additional biological approach to enhancing SC recruitment involves utilising platelet-derived microparticles (PMPs). PMPs are the predominant subtype of microparticle found in peripheral blood, with numbers increased in patients with inflammatory disorders. PMPs can ‘coat’ neutrophils and increase leukocyte-endothelial interactions. Based on this phenomena, we demonstrated that coating HSCs with PMPs prior to infusion in mice enhanced their recruitment in chronically injured colitis colon. We have recently performed parallel intravital studies to investigate the kinetics of MSC homing in vivo. Preliminary studies suggest distribution of MSCs post-infusion is not increased in injured tissue compared to healthy controls – this differs from HSC data. Our understanding of the molecular mechanisms underlying SC homing to sites of injury is increasing and allowing us to develop strategies that can modulate their adhesion. Our ongoing studies have demonstrated that enhancing HSC presence confers a greater anti-inflammatory effect within the local microcirculation. While it is easy to presume that enhanced SC recruitment may be beneficial in models of injury, we should be wary that an “over-recruitment” may have deleterious effects. Certainly, MSCs can behave pro-fibrotically and may worsen the local tissue milieu in conditions of injury. Whether enhancing local MSC presence proves beneficial or detrimental is currently being investigated. Supported by the British Heart Foundation