While encapsulation of cells within protective nanoporous gel cocoons increases cell retention and pro-survival integrin signaling, the influence of cocoon size and intra-capsular cell-cell interactions on therapeutic repair are unknown. Here, we employ a microfluidic platform to dissect the impact of cocoon size and intracapsular cell number on the regenerative potential of transplanted heart explant-derived cells. Deterministic increases in cocoon size boosted the proportion of multicellular aggregates within cocoons, reduced vascular clearance of transplanted cells and enhanced stimulation of endogenous repair. The latter being attributable to cell-cell stimulation of cytokine and extracellular vesicle production while also broadening of the miRNA cargo within extracellular vesicles. Thus, by tuning cocoon size and cell occupancy, the paracrine signature and retention of transplanted cells can be enhanced to promote paracrine stimulation of endogenous tissue repair.

虽然将细胞包封在保护性纳米多孔凝胶茧中可增加细胞滞留率和生存前整合素信号传导，但茧大小和囊内细胞间相互作用对治疗修复的影响尚不清楚。在这里，我们采用微流控平台来剖析茧大小和荚膜内细胞数量对移植的心脏外植体细胞再生潜力的影响。确定性增加茧的大小会增加茧中多细胞聚集体的比例，减少移植细胞的血管清除率，并增强对内源性修复的刺激。后者可归因于细胞因子对细胞因子的刺激和细胞外囊泡的产生，同时也扩大了细胞外囊泡内的miRNA货物。因此，通过调整茧的大小和细胞的占有率，