Applications, challenges and prospects of mesenchymal stem cell exosomes in regenerative medicine

Abstract

Recent advances in the identification and application of different stem cell types have offered alternative therapeutic approaches for clinicians. The lack of successful engraftment, migration into the injured site, loss of functionality and viability, ethical issues, shortage of donated allogeneic stem cells and the possibility of transmission of infectious are the main challenges associated with direct cell transplantation. The discovery and research on exosomes have led to the rise of hopes for the alleviation of different pathologies in regenerative medicine. Exo are nano-sized extracellular vesicles (40–150 nm) and released by each type. These nanoparticles participate in cell-to-cell communication in a paracrine manner. It is thought that the application of Exo can circumvent several drawbacks related to whole-cell therapies. Because of their appropriate size and stability, Exo are touted as therapeutic bullets transferring signaling factors into the acceptor cells in a paracrine manner. Despite these advantages, technologies associated with Exo isolation and purification are challenging because of heterogeneity in exosomal size and cargo. The lack of standard GMP-grade protocols is the main hurdle that limits the extensive application of Exo in the clinical setting. Here, the authors aimed to inspire a logical and realistic vision about problems associated with Exo application in regenerative medicine.

Chronic obstructive pulmonary disease and asthma: mesenchymal stem cells and their extracellular vesicles as potential therapeutic tools

“…In general, these MSCs express surface markers, such as CD105, CD90, and CD73, but not CD34, CD45, CD19, CD11b, CD79α, and CD14 [ 36 – 38 ]. MSCs pose broad anti-inflammatory, immunoregulatory and regenerative features [ 39 – 42 ]. It has been elucidated that EVs secreted from MSCs have key role in mediating biological processes, for example blood coagulation, stem cell differentiation, immunomodulation, and regeneration as well as angiogenesis and etc.…”

Application of exosomes in the diagnosis and treatment of pancreatic diseases

“…Among the extracellular vesicles released from mammalian cells (namely, exosomes, microvesicles, and apoptotic vesicles), exosomes are the most broadly investigated. Exosomes originate from the membranes of multivesicular bodies; they appear as double-layer phospholipid membrane structures in electron microscopy, of diameters ranging from 40 to 150 nm [ 25 ]. Under physiological or pathological conditions, exosomes can transfer bioactive molecules such as DNA, RNAs, and proteins locally or remotely from donor cells to recipient cells [ 26 ].…”

Emerging role of exosomes in the pathology of chronic obstructive pulmonary diseases; destructive and therapeutic properties

“…Lack of enough knowledge related to whole Exo dose (single or repeat injection), route and time of administration, lack of standard GMP protocol, and the possibility of side effects limit the extensive application of Exo in COPD patients. Besides, standard methods have not been introduced for Exo isolation and purification, leading to heterogeneity in Exo population and content [ 150 ].…”