neuroblastoma or primary neurons in the hippocampus improved amyloid plaque
burden by clearing them by microglia [18]. These results provide the evidence of
exosomes’ potential for non-invasive therapeutic use of exosomes in neurological
disorders including CNS demyelinating disease like multiple sclerosis and neurodegenerative disease like AD.
9.2.2 Cardiovascular System
Heart and cardiovascular system work for blood circulation under the highly
synchronized regulation of myocardial contraction. Cardiomyocytes, smooth
muscle cells, endothelial cells, fibroblasts and cardiac stem cells contribute to the
organization and maintenance of the system. For the well-regulated circulation,
cell-to-cell communication is really important. Traditionally, paracrine effect via
growth-factor, endocrine effect via adiponectin, direct cell-to-cell contact via gap
junction, and adhesion molecules like integrin have been regarded as important
players for this effective cell-to-cell communication. Recently, exosomes have
been implicated as another mediator of cell-to-cell communication in myocardial
system in either physiology or pathological condition such as reperfusion injury.
Paracrine effect of pluripotent cells like MSC or cardiac progenitor cells
(CPC) via exosomal delivery to ischemic injured myocardium has been tested in
several studies in vivo.
Intravenously injected MSC-derived exosomes reduced infarct size in mice
model of cardiac ischemic reperfusion injury [19], which was mediated by transfer
of glycolytic enzymes enriched in MSC-derived exosomes that enhanced glycolytic
flux and adenosine triphosphate (ATP) production by complementation of depleted
energetic enzymes in reperfused myocardium [20]. Additionally, membrane-bound
CD73 on MSC-derived exosomes hydrolyzed adenosine monophosphate degraded
from ATPs and adenosine diphosphates in injured cardiomyocytes, to adenosine,
and subsequently interrupted activation of reperfusion injury salvage kinase (RISK)
pathway participating in apoptosis of reperfused myocardium [21]. Meanwhile,
CPC-derived exosomes which are highly enriched in miRNAs including miR-451,
miR-210, miR-132, and miR-146a-3p protected ischemic myocardium via inhibition of apoptosis of cardiomyoblasts in mice model of acute ischemic reperfusion
injury [22, 23]. Cardioprotective effect of exosomes was also mediated by heat
shock protein (HSP) 70 on exosomes by activation of a pathway downstream of
toll-like receptor 4—extracellular signal regulated protein kinases (ERK) 1/2—p38
mitogen-activated protein kinase (p38MAPK)—phosphorylation of HSP27 [24].
A recent meta-analysis study proved the therapeutic and protective effect of
MSC-derived exosomes on cardiac ischemic reperfusion injury [25].
9 Endogenous Radionanomedicine: Validation of Therapeutic Potential
171
burden by clearing them by microglia [18]. These results provide the evidence of
exosomes’ potential for non-invasive therapeutic use of exosomes in neurological
disorders including CNS demyelinating disease like multiple sclerosis and neurodegenerative disease like AD.
9.2.2 Cardiovascular System
Heart and cardiovascular system work for blood circulation under the highly
synchronized regulation of myocardial contraction. Cardiomyocytes, smooth
muscle cells, endothelial cells, fibroblasts and cardiac stem cells contribute to the
organization and maintenance of the system. For the well-regulated circulation,
cell-to-cell communication is really important. Traditionally, paracrine effect via
growth-factor, endocrine effect via adiponectin, direct cell-to-cell contact via gap
junction, and adhesion molecules like integrin have been regarded as important
players for this effective cell-to-cell communication. Recently, exosomes have
been implicated as another mediator of cell-to-cell communication in myocardial
system in either physiology or pathological condition such as reperfusion injury.
Paracrine effect of pluripotent cells like MSC or cardiac progenitor cells
(CPC) via exosomal delivery to ischemic injured myocardium has been tested in
several studies in vivo.
Intravenously injected MSC-derived exosomes reduced infarct size in mice
model of cardiac ischemic reperfusion injury [19], which was mediated by transfer
of glycolytic enzymes enriched in MSC-derived exosomes that enhanced glycolytic
flux and adenosine triphosphate (ATP) production by complementation of depleted
energetic enzymes in reperfused myocardium [20]. Additionally, membrane-bound
CD73 on MSC-derived exosomes hydrolyzed adenosine monophosphate degraded
from ATPs and adenosine diphosphates in injured cardiomyocytes, to adenosine,
and subsequently interrupted activation of reperfusion injury salvage kinase (RISK)
pathway participating in apoptosis of reperfused myocardium [21]. Meanwhile,
CPC-derived exosomes which are highly enriched in miRNAs including miR-451,
miR-210, miR-132, and miR-146a-3p protected ischemic myocardium via inhibition of apoptosis of cardiomyoblasts in mice model of acute ischemic reperfusion
injury [22, 23]. Cardioprotective effect of exosomes was also mediated by heat
shock protein (HSP) 70 on exosomes by activation of a pathway downstream of
toll-like receptor 4—extracellular signal regulated protein kinases (ERK) 1/2—p38
mitogen-activated protein kinase (p38MAPK)—phosphorylation of HSP27 [24].
A recent meta-analysis study proved the therapeutic and protective effect of
MSC-derived exosomes on cardiac ischemic reperfusion injury [25].
9 Endogenous Radionanomedicine: Validation of Therapeutic Potential
171