Cell therapies to treat critical limb ischaemia have demonstrated only modest results in clinical trials, and this has been partly attributed to poor cell retention following their delivery directly into the ischaemic limb. The aim of this study was to determine whether alginate encapsulation of therapeutic pro-angio/arteriogenic macrophages enhances their retention and ultimately improves limb perfusion. A reproducible GMP-compliant method for generating 300 µm alginate capsules was developed to encapsulate pro-angio/arteriogenic macrophages. Longitudinal analysis revealed no detrimental effect of encapsulation on cell number or viability in vitro, and macrophages retained their pro-angio/arteriogenic phenotype. Intramuscular delivery of encapsulated macrophages into the murine ischaemic hindlimb demonstrated increased cell retention compared with injection of naked cells (P = 0.0001), and that this was associated both enhanced angiogenesis (P = 0.02) and arteriogenesis (P = 0.03), and an overall improvement in limb perfusion (P = 0.0001). Alginate encapsulation of pro-angio/arteriogenic macrophages enhances cell retention and subsequent limb reperfusion in vivo. Encapsulation may therefore represent a means of improving the efficacy of cell-based therapies currently under investigation for the treatment of limb ischaemia.

用于治疗严重肢体缺血的细胞疗法在临床试验中仅显示出适度的结果，这部分归因于细胞直接进入缺血肢体后细胞滞留不良。本研究的目的是确定治疗性促血管/动脉生成巨噬细胞的海藻酸盐包封是否增强了它们的保留并最终改善了肢体灌注。开发了一种可重现的 GMP 兼容方法来生成 300 µm 藻酸盐胶囊，以封装促血管/动脉巨噬细胞。纵向分析显示封装对体外细胞数量或活力没有不利影响，巨噬细胞保留了它们的促血管/动脉生成表型。P  = 0.0001），这与增强的血管生成（P  = 0.02）和动脉生成（P  = 0.03）以及肢体灌注的整体改善（P  = 0.0001）有关。海藻酸盐包裹促血管/动脉巨噬细胞可增强体内细胞滞留和随后的肢体再灌注。因此，封装可能代表了一种提高目前正在研究的用于治疗肢体缺血的基于细胞的疗法的功效的手段。