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Embryonic Stem Cell Derived Exosomes Enhance Cardiac Stem Cell Differentiation into Heart Cells

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Date Issued:
2018
Abstract/Description:
Transplantation of embryonic stem (ES) cells into the ischemic and infarcted heart has proven to repopulate cardiac cell populations, attenuate structural cardiac remodeling, and rescue cardiac function. Unfortunately, the pluripotency of ES cells increases risk of teratoma formation in vivo. Exosomes, smaller in comparison to ES cells, are cell free carriers of miRNA, proteins, and lipids, and do not suggest risk of teratoma formation. Exosomes have been proposed to mediate and attenuate regeneration following myocardial infarction (MI), however, the role of exosomes derived from ES cells (ES-Exo) in activating resident cardiac stem cells (CSCs) to undergo cardiac differentiation is not established. In the present study, Stem cell antigen 1 positive (Sca-1+ve) CSCs were isolated, incubated with exosomes, and evaluated for differentiation into the major heart cell types in vitro. Observations of in vitro cardiac differentiation were further established in an in vivo model of MI. Ligation of the coronary artery, or a sham surgery was performed in C57BL/6 mice 8-12 weeks of age. Mice were split among four study groups: sham, MI, MI + H9c2-Exo (a cell line control), (&) MI + ES-Exo. ES-Exo were transplanted via intramyocardial (IM) injection immediately following coronary artery ligation. At day 14 (D14), echocardiography was used to evaluate cardiac function. Differentiation into the major heart cells was determined by sarcomeric ?-actin (cardiomyocytes) and smooth muscle ?-actin (vascular smooth muscle cells) immunostaining. Hematoxylin and Eosin and Masson's Trichrome staining assessed cardiomyocyte hypertrophy and fibrosis, respectively. Immunostaining for major heart cellular markers revealed significant activation of resident Sca-1+ve CSCs to undergo cardiac differentiation after ES-Exo treatment. Cardiomyocyte hypertrophy and myocardial fibrosis were significantly increased following coronary artery ligation. Results from histological staining revealed significantly decreased levels of hypertrophy and fibrosis in hearts transplanted with ES-Exo following coronary ligation. In summary, our findings advocate ES-Exo as a viable treatment option to repopulate the myocardium with viable heart cells, attenuate cardiac remodeling, and rescue cardiac function.
Title: Embryonic Stem Cell Derived Exosomes Enhance Cardiac Stem Cell Differentiation into Heart Cells.
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Name(s): Hammond, Jamillah, Author
Singla, Dinender, Committee Chair
Masternak, Michal, Committee Member
Davidson, Victor, Committee Member
University of Central Florida, Degree Grantor
Type of Resource: text
Date Issued: 2018
Publisher: University of Central Florida
Language(s): English
Abstract/Description: Transplantation of embryonic stem (ES) cells into the ischemic and infarcted heart has proven to repopulate cardiac cell populations, attenuate structural cardiac remodeling, and rescue cardiac function. Unfortunately, the pluripotency of ES cells increases risk of teratoma formation in vivo. Exosomes, smaller in comparison to ES cells, are cell free carriers of miRNA, proteins, and lipids, and do not suggest risk of teratoma formation. Exosomes have been proposed to mediate and attenuate regeneration following myocardial infarction (MI), however, the role of exosomes derived from ES cells (ES-Exo) in activating resident cardiac stem cells (CSCs) to undergo cardiac differentiation is not established. In the present study, Stem cell antigen 1 positive (Sca-1+ve) CSCs were isolated, incubated with exosomes, and evaluated for differentiation into the major heart cell types in vitro. Observations of in vitro cardiac differentiation were further established in an in vivo model of MI. Ligation of the coronary artery, or a sham surgery was performed in C57BL/6 mice 8-12 weeks of age. Mice were split among four study groups: sham, MI, MI + H9c2-Exo (a cell line control), (&) MI + ES-Exo. ES-Exo were transplanted via intramyocardial (IM) injection immediately following coronary artery ligation. At day 14 (D14), echocardiography was used to evaluate cardiac function. Differentiation into the major heart cells was determined by sarcomeric ?-actin (cardiomyocytes) and smooth muscle ?-actin (vascular smooth muscle cells) immunostaining. Hematoxylin and Eosin and Masson's Trichrome staining assessed cardiomyocyte hypertrophy and fibrosis, respectively. Immunostaining for major heart cellular markers revealed significant activation of resident Sca-1+ve CSCs to undergo cardiac differentiation after ES-Exo treatment. Cardiomyocyte hypertrophy and myocardial fibrosis were significantly increased following coronary artery ligation. Results from histological staining revealed significantly decreased levels of hypertrophy and fibrosis in hearts transplanted with ES-Exo following coronary ligation. In summary, our findings advocate ES-Exo as a viable treatment option to repopulate the myocardium with viable heart cells, attenuate cardiac remodeling, and rescue cardiac function.
Identifier: CFE0007188 (IID), ucf:52254 (fedora)
Note(s): 2018-08-01
M.S.
Medicine, Biomedical Sciences
Masters
This record was generated from author submitted information.
Subject(s): Myocardial Infarction Cardiac Regeneration Stem Cell Exosomes
Persistent Link to This Record: http://purl.flvc.org/ucf/fd/CFE0007188
Restrictions on Access: campus 2023-08-15
Host Institution: UCF

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