title: Human Induced Pluripotent Stem Cell-Derived Microvesicles Transmit RNAs and Proteins to Recipient Mature Heart Cells Modulating Cell Fate and Behavior.
abstract: Microvesicles (MVs) are membrane-enclosed cytoplasmic fragments released by normal and activated cells that have been described as important mediators of cell-to-cell communication. Although the ability of human induced pluripotent stem cells (hiPSCs) to participate in tissue repair is being increasingly recognized, the use of hiPSC-derived MVs (hiPSC-MVs) in this regard remains unknown. Accordingly, we investigated the ability of hiPSC-MVs to transfer bioactive molecules including mRNA, microRNA (miRNA), and proteins to mature target cells such as cardiac mesenchymal stromal cells (cMSCs), and we next analyzed effects of hiPSC-MVs on fate and behavior of such target cells. The results show that hiPSC-MVs derived from integration-free hiPSCs cultured under serum-free and feeder-free conditions are rich in mRNA, miRNA, and proteins originated from parent cells; however, the levels of expression vary between donor cells and MVs. Importantly, we found that transfer of hiPSC components by hiPSC-MVs impacted on transcriptome and proteomic profiles of target cells as well as exerted proliferative and protective effects on cMSCs, and enhanced their cardiac and endothelial differentiation potential. hiPSC-MVs also transferred exogenous transcripts from genetically modified hiPSCs that opens new perspectives for future strategies to enhance MV content. We conclude that hiPSC-MVs are effective vehicles for transferring iPSC attributes to adult somatic cells, and hiPSC-MV-mediated horizontal transfer of RNAs and proteins to injured tissues may be used for therapeutic tissue repair. In this study, for the first time, we propose a new concept of use of hiPSCs as a source of safe acellular bioactive derivatives for tissue regeneration.
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Bobis-Wozowicz
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kmiotek
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.|Malopolska Centre of Biotechnology, Krakow, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Sekula
authors.affiliation: Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Kedracka-Krok
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kamycka
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Adamiak
authors.affiliation: Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.|Malopolska Centre of Biotechnology, Krakow, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Jankowska
authors.affiliation: Department of Medical Genetics, Chair of Pediatrics, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Madetko-Talowska
authors.affiliation: Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.|Malopolska Centre of Biotechnology, Krakow, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Sarna
authors.affiliation: Department of Pediatric Cardiac Surgery, Polish-American Children's Hospital, Krakow, Poland.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Bik-Multanowski
authors.affiliation: Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kolcz
authors.affiliation: Polish Stem Cell Bank, Warsaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Boruczkowski
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Madeja
authors.affiliation: Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of Kansas Medical Center, Kansas City, KS 66160, Kansas, USA.
authors.forename: Buddhadeb
authors.initials: B
authors.lastname: Dawn
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Ewa K
authors.initials: EK
authors.lastname: Zuba-Surma
mesh_terms: D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D016895:Culture Media, Serum-Free; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Cell signaling; Induced pluripotent stem cells; Microvesicles; Paracrine activity; Tissue regeneration