Secretome signature of cardiopoietic cells echoed in rescued infarcted heart proteome,STEM CELLS Translational Medicine

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Secretome signature of cardiopoietic cells echoed in rescued infarcted heart proteome
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2021-05-28 , DOI: 10.1002/sctm.20-0509
D Kent Arrell _{1,

2,

3} , Ruben J Crespo-Diaz _{1,

2,

3,

4} , Satsuki Yamada _{1,

2,

5} , Ryounghoon Jeon _{1,

2} , Armin Garmany _{1,

2,

6} , Sungjo Park _{1,

2} , Jeffrey P Adolf _{1,

2} , Christopher Livia _{1,

2,

6} , Matthew L Hillestad _{1,

2} , Jozef Bartunek ₇ , Atta Behfar _{1,

2,

3,

8} , Andre Terzic _{1,

2,

3,

9}

Affiliation

Stem cell paracrine activity is implicated in cardiac repair. Linkage between secretome functionality and therapeutic outcome was here interrogated by systems analytics of biobanked human cardiopoietic cells, a regenerative biologic in advanced clinical trials. Protein chip array identified 155 proteins differentially secreted by cardiopoietic cells with clinical benefit, expanded into a 520 node network, collectively revealing inherent vasculogenic properties along with cardiac and smooth muscle differentiation and development. Next generation RNA sequencing, refined by pathway analysis, pinpointed miR-146 dependent regulation upstream of the decoded secretome. Intracellular and extracellular integration unmasked commonality across cardio-vasculogenic processes. Mirroring the secretome pattern, infarcted hearts benefiting from cardiopoietic cell therapy restored the disease proteome engaging cardiovascular system functions. The cardiopoietic cell secretome thus confers a therapeutic molecular imprint on recipient hearts, with response informed by predictive systems profiling.

中文翻译：

心肌细胞的分泌组特征在挽救的梗塞心脏蛋白质组中得到回响

干细胞旁分泌活动与心脏修复有关。分泌组功能和治疗结果之间的联系在这里被生物库人类心脏生成细胞的系统分析所质疑，这是一种先进临床试验中的再生生物制品。蛋白质芯片阵列识别出 155 种由心肌细胞差异分泌的具有临床益处的蛋白质，扩展成一个 520 个节点的网络，共同揭示了固有的血管生成特性以及心脏和平滑肌的分化和发育。通过通路分析完善的下一代 RNA 测序确定了已解码分泌组上游的 miR-146 依赖性调节。细胞内和细胞外整合揭示了心血管发生过程的共性。反映分泌组模式，受益于心脏生成细胞疗法的梗塞心脏恢复了参与心血管系统功能的疾病蛋白质组。因此，心脏生成细胞分泌组赋予受体心脏治疗性分子印记，反应由预测系统分析提供。

更新日期：2021-05-28

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