Kanda Pushpinder, Benavente-Babace Ainara, Parent Sandrine, Connor Michie, Soucy Nicholas, Steeves Alexander, Lu Aizhu, Cober Nicholas David, Courtman David, Variola Fabio, Alarcon Emilio I, Liang Wenbin, Stewart Duncan J, Godin Michel, Davis Darryl R
University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine, University of Ottawa, Ottawa, K1Y4W7, Canada.
Department of Physics, University of Ottawa, K1N6N5, Canada.
Biomaterials. 2020 Jul;247:120010. doi: 10.1016/j.biomaterials.2020.120010. Epub 2020 Apr 2.
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.
虽然将细胞包裹在保护性纳米多孔凝胶茧中可增加细胞保留率和促生存整合素信号传导，但茧大小和囊内细胞间相互作用对治疗性修复的影响尚不清楚。在此，我们采用微流控平台来剖析茧大小和囊内细胞数量对移植的心脏外植体来源细胞再生潜力的影响。茧大小的确定性增加提高了茧内多细胞聚集体的比例，减少了移植细胞的血管清除率，并增强了对内源性修复的刺激。后者归因于细胞间对细胞因子和细胞外囊泡产生的刺激，同时也拓宽了细胞外囊泡内的miRNA负载。因此，通过调节茧大小和细胞占有率，可以增强移植细胞的旁分泌特征和保留率，以促进对内源性组织修复的旁分泌刺激。
