6.4 Biomedical Application of EVs
Over the past decades, there have been extensive researches carried out on EVs
as a potential diagnostic biomarker discovery and a therapeutic development
[51–53]. Disease-associated EVs are known to shuttle disease specific biomolecules such as abnormal RNAs and oncoproteins to the recipient cells, leading to
the reprogramming of recipient target cells. Since abnormal cells continuously
release the EVs which circulate in the blood stream, EVs that are likely to contain
disease-related markers can be simply isolated from the biofluids such as blood
and urine: EVs isolated from biofluids are harnessed as promising circulating
diagnostic biomarkers without invasive manner. In tumor development and progress, cells require multistage process of tumorigenesis: EVs as intercellular
communicators, facilitate tumorigenesis by transferring their chemokine receptors,
oncogenes, and oncoproteins. Recent studies demonstrated that differences
between their vesicular protein and nucleic acid cargos of cancer EVs and normal
cell-derived EVs make possible for EV-based cancer diagnostics [54–56]. It is
becoming increasingly clear that EV-associated miRNAs are potential diagnostic
and prognostic indicators against many different types of cancer by providing
evidence that vesicular miRNAs are positively correlated with the advanced
cancer stages [57, 58].
EVs hold the great promise in wide range of therapeutic application in alternative regenerative medicine, drug delivery system, and biosensing platform
including radionanomedicine. More details on EV-based therapeutic potential are
reviewed in the following Chap. 9, “Validation of Therapeutic Potential”. As for the
harnessing of EVs as drug delivery carrier, because original job of EVs is to deliver
the bioactive molecules to relevant target recipient cells in our body, EVs can be
used as drug delivery conveyor by loading exogenous chemical or nucleic acid
drugs into the EVs. When compared with other drug delivery systems, EV-based
drug delivery conveyer has substantial advantages such as the drug loading capacity
to vesicular lumen, long half-life in blood stream, membrane penetration ability,
intrinsic homing capability, and feasible membrane modification to increase blood
half-life and targeting capacity. The short interfering RNA (siRNA)-loaded EVs are
effective to induce cancer cell death via post-transcriptional gene silencing [59, 60].
Therapeutic functions of EVs have been reported predominantly in stem cells,
which exhibit the ability to induce angiogenic programs in quiescent endothelial
cells [61, 62], suppress apoptosis and stimulate cell proliferation [63, 64], deliver
immunomodulatory signals, as well as recruit and/or reprogram cells that are
required for tissue regeneration [24]. Stem cell-based therapy has also been
intensively investigated in its potential use for the treatment of degenerative diseases. However, many challenges, such as undesirable cancer formation and ethical
issues still remains as unsolved risk factors. Because stem cell-derived EVs harbor
the biofunctional molecules of stem cells, those EVs have been considered as
alternative therapeutic drug to stem cell therapeutics. Especially, the therapeutic
134
C. Lee et al.
Over the past decades, there have been extensive researches carried out on EVs
as a potential diagnostic biomarker discovery and a therapeutic development
[51–53]. Disease-associated EVs are known to shuttle disease specific biomolecules such as abnormal RNAs and oncoproteins to the recipient cells, leading to
the reprogramming of recipient target cells. Since abnormal cells continuously
release the EVs which circulate in the blood stream, EVs that are likely to contain
disease-related markers can be simply isolated from the biofluids such as blood
and urine: EVs isolated from biofluids are harnessed as promising circulating
diagnostic biomarkers without invasive manner. In tumor development and progress, cells require multistage process of tumorigenesis: EVs as intercellular
communicators, facilitate tumorigenesis by transferring their chemokine receptors,
oncogenes, and oncoproteins. Recent studies demonstrated that differences
between their vesicular protein and nucleic acid cargos of cancer EVs and normal
cell-derived EVs make possible for EV-based cancer diagnostics [54–56]. It is
becoming increasingly clear that EV-associated miRNAs are potential diagnostic
and prognostic indicators against many different types of cancer by providing
evidence that vesicular miRNAs are positively correlated with the advanced
cancer stages [57, 58].
EVs hold the great promise in wide range of therapeutic application in alternative regenerative medicine, drug delivery system, and biosensing platform
including radionanomedicine. More details on EV-based therapeutic potential are
reviewed in the following Chap. 9, “Validation of Therapeutic Potential”. As for the
harnessing of EVs as drug delivery carrier, because original job of EVs is to deliver
the bioactive molecules to relevant target recipient cells in our body, EVs can be
used as drug delivery conveyor by loading exogenous chemical or nucleic acid
drugs into the EVs. When compared with other drug delivery systems, EV-based
drug delivery conveyer has substantial advantages such as the drug loading capacity
to vesicular lumen, long half-life in blood stream, membrane penetration ability,
intrinsic homing capability, and feasible membrane modification to increase blood
half-life and targeting capacity. The short interfering RNA (siRNA)-loaded EVs are
effective to induce cancer cell death via post-transcriptional gene silencing [59, 60].
Therapeutic functions of EVs have been reported predominantly in stem cells,
which exhibit the ability to induce angiogenic programs in quiescent endothelial
cells [61, 62], suppress apoptosis and stimulate cell proliferation [63, 64], deliver
immunomodulatory signals, as well as recruit and/or reprogram cells that are
required for tissue regeneration [24]. Stem cell-based therapy has also been
intensively investigated in its potential use for the treatment of degenerative diseases. However, many challenges, such as undesirable cancer formation and ethical
issues still remains as unsolved risk factors. Because stem cell-derived EVs harbor
the biofunctional molecules of stem cells, those EVs have been considered as
alternative therapeutic drug to stem cell therapeutics. Especially, the therapeutic
134
C. Lee et al.