THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA;UNIVERSITY OF MARYLAND, BALTIMORE;KAUSHAL, Sunjay;SHARMA, Sudhish;VALLABHAJOSYULA, Prashanth;SAHA, Progyaparamita
The stem cell field is hindered by the inability to noninvasively monitor transplanted cells within a target organ in a repeatable, time sensitive, and condition specific manner. It was hypothesized that the quantitation and intraexosomal cargo characterization of circulating transplanted cell specific exosomes would enable a reliable, noninvasive surveillance platform to reflect the conditional activity of their cellular counterparts. To test this hypothesis, use was made of a human-into-rat-xenogeneic myocardial infarction model involving two well-studied progenitor cell types: cardiosphere-derived cells (CDCs) and c-kit+cardiac progenitor cells (CPCs), derived from the same right atrial appendage of adult humans. To noninvasively monitor the activity of transplanted CDCs or CPCs in vivo, recipient plasma exosomes were purified using antibodies to human leukocyte antigen (HLA) surface molecules only expressed on human exosome surface. After 7 days post-transplantation, a 2.5 fold increase in concentration of plasma CPC-specific exosomes was observed when compared to CDC-specific exosomes. Computational pathway analysis failed to link CPC or CDC cellular mRNA with observed myocardial recovery. However, myocardial recovery was strongly linked to the miRNA cargo of CPC exosomes purified from recipient plasma. In addition, mechanistic pathways governing myocardial recovery were identified to specific outcomes by the 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.Le domaine des cellules souches est gêné par l'incapacité à surveiller de manière non invasive des cellules transplantées dans un organe cible d'une manière reproductible, chronosensible et spécifique à la pathologie. On a avancé l'hypothèse que la quantification et la caractérisation de cargaison intraexosomale d'exosomes circul
