9.2.3 Acute Kidney Injury
Acute kidney injury (AKI) is a disease which is characterized by acute tubular
injury inducing rapid loss of renal function mainly caused by ischemic reperfusion
injury [26]. Several animal studies showed that MSCs have treatment effect to AKI
[27, 28]. Recent evidence has suggested that the effect of MSCs on AKI recovery
relies on paracrine mechanism rather than transdifferentiation of MSCs [29–33].
Exosomes derived from MSCs stimulated proliferation and enhanced resistance of
tubular cells to apoptosis in vitro [34]. In vivo study proved treatment effect of
MSC-derived exosomes on the recovery of AKI via RNA-dependent paracrine
effect [34, 35]. Injection of MSC-derived exosomes into kidney repaired
cisplatin-induced AKI in mice by ameliorating apoptosis by suppressing activation
of the p38MAPK pathway, promoting cell proliferation via activation of the ERK 1/
2 pathway [36]. A meta-analysis concluded that cell-free treatment using
MSC-derived exosomes was better than MSC-conditioned media [37]. Not only
MSC-derived exosomes, endothelial colony-forming cells (ECFC)-derived exosomes also had a protective effect on AKI in mice [38]. PTEN/Akt pathway in
endothelial cells was targeted by miR-486-5p transferred from human cord blood
ECFC via exosomes, which induced the protective effect against AKI [39].
9.3 Tumor
Exosomes participate in intercellular communication even in cancer cells.
Exosomes carry various molecules of nucleic acid, lipid, and protein, and affect
pathological pathways of cancer cells including tumorigenesis, tumor growth,
angiogenesis, metastasis, drug resistance, immune escape, tumor-stroma interaction, and tumor thrombosis [40]. Various molecules of proteins and nucleic acids
contained in exosomes have been evaluated to develop novel diagnostic and
prognostic marker for various types of cancer. The idea to use exosomes as
anti-tumor vaccines or drug cargo for targeted drug delivery has been evaluated
even in clinical trials (Table 9.1, modified from Lener et al. J Extracellular Vesicles
2015) [41].
9.3.1 Anti-tumor Vaccination
Extracellular vesicles derived from antigen presenting cells contain MHC-peptide
complexes stimulated immune response [42]. Safety, feasibility, and efficacy of
vaccination of autologous DC-derived exosomes loaded with tumor antigens were
tested in patients with non-small cell lung cancer (NSCLC) or melanoma in phase I
clinical trials [43, 44]. In phase II clinical trials, administration of autologous
172
S. Ha and D. S. Lee
Acute kidney injury (AKI) is a disease which is characterized by acute tubular
injury inducing rapid loss of renal function mainly caused by ischemic reperfusion
injury [26]. Several animal studies showed that MSCs have treatment effect to AKI
[27, 28]. Recent evidence has suggested that the effect of MSCs on AKI recovery
relies on paracrine mechanism rather than transdifferentiation of MSCs [29–33].
Exosomes derived from MSCs stimulated proliferation and enhanced resistance of
tubular cells to apoptosis in vitro [34]. In vivo study proved treatment effect of
MSC-derived exosomes on the recovery of AKI via RNA-dependent paracrine
effect [34, 35]. Injection of MSC-derived exosomes into kidney repaired
cisplatin-induced AKI in mice by ameliorating apoptosis by suppressing activation
of the p38MAPK pathway, promoting cell proliferation via activation of the ERK 1/
2 pathway [36]. A meta-analysis concluded that cell-free treatment using
MSC-derived exosomes was better than MSC-conditioned media [37]. Not only
MSC-derived exosomes, endothelial colony-forming cells (ECFC)-derived exosomes also had a protective effect on AKI in mice [38]. PTEN/Akt pathway in
endothelial cells was targeted by miR-486-5p transferred from human cord blood
ECFC via exosomes, which induced the protective effect against AKI [39].
9.3 Tumor
Exosomes participate in intercellular communication even in cancer cells.
Exosomes carry various molecules of nucleic acid, lipid, and protein, and affect
pathological pathways of cancer cells including tumorigenesis, tumor growth,
angiogenesis, metastasis, drug resistance, immune escape, tumor-stroma interaction, and tumor thrombosis [40]. Various molecules of proteins and nucleic acids
contained in exosomes have been evaluated to develop novel diagnostic and
prognostic marker for various types of cancer. The idea to use exosomes as
anti-tumor vaccines or drug cargo for targeted drug delivery has been evaluated
even in clinical trials (Table 9.1, modified from Lener et al. J Extracellular Vesicles
2015) [41].
9.3.1 Anti-tumor Vaccination
Extracellular vesicles derived from antigen presenting cells contain MHC-peptide
complexes stimulated immune response [42]. Safety, feasibility, and efficacy of
vaccination of autologous DC-derived exosomes loaded with tumor antigens were
tested in patients with non-small cell lung cancer (NSCLC) or melanoma in phase I
clinical trials [43, 44]. In phase II clinical trials, administration of autologous
172
S. Ha and D. S. Lee