Circulating exosomes derived from transplanted progenitor cells aid the functional recovery of ischemic myocardium

作者：Progyaparamita Saha, Sudhish Sharma, Laxminarayana Korutla, Srinivasa Raju Datla, Farnaz Shoja‐Taheri, Rachana Mishra, Grace Bigham, Malini Sarkar, David Morales, Gregory J. Bittle, Muthukumar Gunasekaran, Chetan Ambastha, Mir Yasir Arfat, Deqiang Li, Andreas Habertheuer, Robert W. Hu, Manu O. Platt, Peixin Yang, Michael Davis, Prashanth Vallabhajosyula, Sunjay Kaushal · 发表于：Science Translational Medicine · 年份：2019 · DOI：10.1126/scitranslmed.aau1168 · 被引用次数：95 · 研究领域：Extracellular vesicles in disease、Transplantation: Methods and Outcomes、Cardiac Structural Anomalies and Repair

cardiac progenitor cells (CPCs), both derived from the right atrial appendage of adults undergoing cardiopulmonary bypass. CPCs outperformed the CDCs in cell-based and in vivo regenerative assays. To noninvasively monitor the activity of transplanted CDCs or CPCs in vivo, we purified progenitor cell-specific exosomes from recipient total plasma exosomes. Seven days after transplantation, the concentration of plasma CPC-specific exosomes increased about twofold compared to CDC-specific exosomes. Computational pathway analysis failed to link CPC or CDC cellular messenger RNA (mRNA) with observed myocardial recovery, although recovery was linked to the microRNA (miRNA) cargo of CPC exosomes purified from recipient plasma. We further identified mechanistic pathways governing specific outcomes related to myocardial recovery associated with transplanted CPCs. Collectively, these findings demonstrate the potential of circulating progenitor cell-specific exosomes as a liquid biopsy that provides a noninvasive window into the conditional state of the transplanted cells. These data implicate the surveillance potential of cell-specific exosomes for allogeneic cell therapies.