Abstract P1070: In Vivo Autotransplantation Of Spleen-derived Endothelial Progenitor Cells To Promote Angiogenesis In Ischemic Sites

Abstract

Since mononuclear cells were first illuminated as potential endothelial progenitor cells (EPCs), bone marrow (BM) was extracted and processed as BM-derived EPCs for autotransplantation to the ischemic sites in previous studies. Still, numerous clinical trials based on this strategy showed only marginal effects, and the small number of BM-derived EPCs was suggested as a possible limitation. Meanwhile, spleen contains abundant mononuclear cells which can inherently target the ischemic sites, and these cells can be primed by hypoxia. If only they can be primed in vivo, spleen-derived EPCs can be inherently autotransplanted to ischemic sites with various advantages such as plentiful cell number, non-invasive extraction and delivery of these cells. In this study, splenic mononuclear cells were utilized to promote angiogenesis in ischemic sites. In vivo priming of splenic mononuclear cells, their inherent targeting and therapeutic effect on ischemic sites were sequentially explored towards the 'in vivo autotransplantation'. For hypoxic priming, the effect of hypoxia and hypoxic-mimetic agent (cobalt chloride) on isolated splenic mononuclear cells were comparable in both priming methods, regarding the morphology changes and the increase in expression of EPC markers. In align with these in vitro results, both hypoxic-mimetic agent-loaded nanoparticle delivery to spleen and splenic artery ligation resulted in increased expression of EPC markers in mice spleen. Moreover, the proportion and actual numbers of the cells presenting EPC marker were significantly higher in primed splenic cells than in BM cells. After the priming, these primed cells not only maintained the inherent targeting ability but also gained the ability to promote angiogenesis. Consequently, these primed cells presented therapeutic effects as evidenced by higher expression of angiogenic markers with enhanced blood flow recovery in mouse hindlimb ischemia model, compared with untreated or BM-derived EPCs' autotransplantation for conventional strategy. For EPC-based treatment of ischemia, 'In vivo autotransplantation' is simple and non-invasive strategy which can overcome the previous limitations of insufficient cell numbers.