Page 462 - IJB-9-2

International Journal of Bioprinting Bioprinting of exosomes

content, and function . The biogenesis of EXOs occurs and metabolic diseases . More recently, EXOs have also
[1]
[14]
through a series of events that is initiated through the shown great potential as regenerative biotherapeutics [4,5] ,
formation of primary endocytic vesicles facilitated by the immunomodulatory factors [18,19] , and drug delivery
inward budding of the plasma membrane . The fusion vehicles due to their unparalleled ability for intracellular
[20]
[2]
of multiple endocytic vesicles results in the formation of crosstalk. For example, EXOs derived from cardiac progenitor
early endosomes that mature into late endosomes and cells have been shown to modulate gene expression in cardiac
eventually multivesicular bodies (MVBs), which are fibroblasts and endothelial cells, exerting a cardioprotective
subsequently released into the extracellular space . EXOs and pro-angiogenic effect in infarcted hearts in vivo .
[4]
[2]
have been found to play a significant role in intercellular In another instance, the internalization of bone marrow
communication and a wide gamut of physiological mesenchymal stem cell (BMMSC) EXOs by chondrocytes
[3]
processes, including tissue repair [4,5] , maintenance of stem harvested from patients with osteoarthritis demonstrated
cell phenotype , immune response , and pathological that tumor necrosis factor-alpha-induced inflammatory
[7]
[6]
processes, such as cardiovascular disease , ocular effects were inhibited, while the production of collagen (Col)
[8]
conditions , neurodegeneration , and autoimmune II and proteoglycans (PGs) was upregulated by these cells
[10]
[9]
disorders [11,12] . Over the past decade, EXOs have garnered in vitro . The EXO-mediated transfer of microRNA-23b-
[21]
widespread attention as emerging diagnostic biomarkers 3p that is secreted from mechanically stimulated Schwann
of diseases and as potential cell-free nanotherapeutics for cells has also been shown to promote neurite outgrowth
[2]
the treatment of various pathological conditions [13,14] . in vitro and enhance axonal regeneration in a sciatic nerve
[22]
EXOs have long served as novel biomarkers in clinical injury rat model in vivo . Furthermore, studies have
diagnostics on account of their contents, including proteins revealed that MSC-derived EXOs exert anti-inflammatory
and nucleic acids, such as deoxyribonucleic acid (DNA), effects by suppressing macrophage activation through the
messenger ribonucleic acids (mRNAs), and microRNAs inhibition of nuclear factor kappa B (NF-kB) signaling
(miRNAs), which serve as reliable predictors of disease cascade to modulate foreign body responses to implanted
[18,19]
progression . Studies have shown that in certain types of biomaterials in vivo . More recently, EXOs have been
[2]
cancers, tumor cells release EXOs at a significantly higher engineered to deliver exogenous therapeutic moieties to
amount compared to normal cells [15,16] . Moreover, the recipient cells for use as targeted drug delivery vehicles in
[23,24]
exosomal cargo released by unhealthy cells possesses a various applications, including cancer . Moreover, EXOs
unique expression signature that is specific to a particular have been investigated as biotherapeutics in numerous
[14]
pathological condition . Owing to this distinctive clinical trials for addressing a wide range of conditions .
[17]
attribute, EXOs have been widely considered crucial for Additionally, several companies are actively investigating
clinical diagnosis of various pathological conditions, clinical grade EXOs for the treatment of various clinical
including cancer and other neurodegenerative, infectious, indications, as presented in Table 1.
Table 1. List of major companies developing therapeutic EXOs for various clinical indications
Company Product Cell source Indication Clinical trial
Aegle Therapeutics AGLE 102 BMMSCs Dystrophic epidermolysis bullosa Phase 1/2a
Exopharm Plexaris Platelets Wound healing Phase 1
United Therapeutics UNEX-42 BMMSCs Bronchopulmonary dysplasia Phase 1
Direct Biologics ExoFlo BMMSCs ARDS Investigational new drug
Organicell Zofin Perinatal COPD, COVID-19, osteoarthritis Phase 1/2
exoIL-12 Engineered MSCs Cutaneous T-cell lymphoma Phase 1
Codiak Biosciences exoSTING Solid tumors Phase 1
exoASO-STAT6 Myeloid-rich cancers Phase 1
Avalon Globocare AVA-201 Engineered MSCs Oral cancers Phase 1
Evox Therapeutics DeliverEx platform with Engineered MSCs Niemann–Pick disease type C Pre-clinical
transmembrane protein cargo
Ilias Biologics ILB-202 Engineered MSCs Acute inflammatory diseases Phase 1
Capricor CAP-2003 Cardiospheres Duchenne muscular dystrophy Pre-clinical
Abbreviations: ARDS, acute respiratory distress syndrome; BMMSC, bone marrow-derived mesenchymal stem cells; COPD, chronic obstructive pulmo-
nary disease; COVID-19, coronavirus disease 2019; MSC, mesenchymal stem cells.

Volume 9 Issue 2 (2023) 454 https://doi.org/10.18063/ijb.690