Page 50 - Exosomes - wound healing power

Int. J. Mol. Sci. 2021, 22, 3130 10 of 15
Int. J. Mol. Sci. 2021, 22, x FOR PEER REVIEW 10 of 15

Figure 4. Schematic representation of engineering approaches towards clinical applications.
Figure 4. Schematic representation of engineering approaches towards clinical applications.
6. Current Limitations of EVs/Exs-Based Therapeutic Strategies
The combination of gene editing technics to create modified EVs/Exs with addition
of biomaterials such as hydrogel encapsulation and composite-loaded wound dressing
Cell-free EVs/Exs-based therapeutics permit to avoid some limitations of SC-based
are highly promising for management of chronic skin inflammation. However, these con-
strategies including eventual rejection and short persistence while almost acting in a similar
cepts are still at their infancy and call upon furthering investigations to reach the clinical
manner as whole cells. Despite considerable advances in the field, successful clinical
translation of EVs/Exs-based nanomedicine to help patients suffering from chronic skin
translation of these promising therapeutic strategies is still facing various challenges.
The low
inflammation. productivity of pure EVs/EVs is among the first concerns because therapy
requires large amounts. The poor yield after isolation, could indeed limit sufficient pro-
6. Current Limitations of EVs/Exs-Based Therapeutic Strategies
duction for large-scale development for therapy. Some conditions like hypoxia or pH
modifications can increase EVs/Exs yield, but such cells conditioning prior to EVs/Exs
Cell-free EVs/Exs-based therapeutics permit to avoid some limitations of SC-based
isolation could modify their “cargo” and decrease their purity. To what extent EVs/Exs
strategies including eventual rejection and short persistence while almost acting in a sim-
should be pure depends on the experimental question and end usage. High purity is a
ilar manner as whole cells. Despite considerable advances in the field, successful clinical
must to attribute a function, but less purity and higher quantity are in general required for
translation of these promising therapeutic strategies is still facing various challenges.
most therapeutic strategies where function is paramount not the definitive association of
The low productivity of pure EVs/EVs is among the first concerns because therapy
function with EVs/Exs. Several studies also indicated that the composition of the EVs/Exs
requires large amounts. The poor yield after isolation, could indeed limit sufficient pro-
“cargo” be it proteins or RNAs can be different and depends on different purification
duction for large-scale development for therapy. Some conditions like hypoxia or pH
methods [97]. miRNA and potentially other molecules from the EVs/Exs “cargo” could
modifications can increase EVs/Exs yield, but such cells conditioning prior to EVs/Exs iso-
cause undesirable effects, such as tumorigenesis, which may be caused by differences
lation could modify their “cargo” and decrease their purity. To what extent EVs/Exs
contaminating products. Thus, EVs/Exs collected with different methods, could differ
should be pure depends on the experimental question and end usage. High purity is a
in many aspects and properties, and there is no one-size-fits all procedure; mainly a bal-
must to attribute a function, but less purity and higher quantity are in general required
ance between purity and quantity in function of EVs/Exs end-use to preserve particles
for most therapeutic strategies where function is paramount not the definitive association
properties and reduce the risk of adverse effects.
of function with EVs/Exs. Several studies also indicated that the composition of the
The eventual misallocation of EVs/Exs at sites other than the intended target upon
EVs/Exs “cargo” be it proteins or RNAs can be different and depends on different purifi-
administration is another current concern calling upon furthering the understanding of
cation methods [97]. miRNA and potentially other molecules from the EVs/Exs “cargo”
EVs/Exs bio-distribution to increase benefit and avoid undesired effects. The biology of
could cause undesirable effects, such as tumorigenesis, which may be caused by differ-
miRNA is complex, and a given molecule could induce distinct and even opposite effects
ences contaminating products. Thus, EVs/Exs collected with different methods, could dif-
in different tissues. It means that administration of EVs/Exs therapy needs improvement
fer in many aspects and properties, and there is no one-size-fits all procedure; mainly a
to permit specific organs targeting.