Current developments and therapeutic potentials of Exosomes from Induced pluripotent stem cells (iPSCs)-derived mesenchymal stem cells (iMSCs)

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells derived from adult human tissues that have the ability to proliferate in vitro and maintain their multipotency, making them attractive cell sources for regenerative medicine. However, MSCs reportedly show limited proliferative capacity with inconsistent therapeutic outcomes due to their heterogeneous nature. On the other hand, induced pluripotent stem cells (iPSC) have emerged as an alternative source for the production of various specialized cell types via their ability to differentiate from all three primary germ layers, leading to applications in regenerative medicine, disease modeling, and drug therapy. Notably, iPSCs can differentiate into MSCs in monolayer, commonly referred to as induced mesenchymal stem cells (iMSCs). These cells show superior therapeutic qualities compared with adult MSCs as the applications of the latter are restricted by passage number and autoimmune rejection when applied in tissue regeneration trials. Furthermore, increasing evidence shows that the therapeutic properties of stem cells are a consequence of the paracrine effects mediated by their secretome such as from exosomes, a type of extracellular vesicle secreted by most cell types. Several studies that investigated the potential of exosomes in regenerative medicine and therapy have revealed promising results. Therefore, this review focuses on the recent findings of exosomes secreted from iMSCs as a potential noncell-based therapy.

Application of stem cells in regeneration medicine

“…[193][194][195] Exosomes are products of the paracrine mechanism of stem cells, are more rapidly utilized than stem cells themselves, and have a wide range of clinical applications. [196][197][198] Regev-Rudzki N et al 194 examined the therapeutic effects of MSC-Exos during fracture healing in a CD9−/− mouse model and found that MSC-Exos were effective in promoting fracture healing. Zhang et al 199 reported results of implanting human embryonic-derived exosomes in a rat model of cartilage defect and found that exosome treatment resulted in the complete recovery of cartilage and subchondral bone by the 12th week.…”

“…Exosomes are tiny vesicles secreted by living cells 191,192 that carry relevant proteins, lipids, nucleic acids, and other substances derived from late endonucleosomal multivesicular bodies, which play an important role in intercellular information transfer 193–195 . Exosomes are products of the paracrine mechanism of stem cells, are more rapidly utilized than stem cells themselves, and have a wide range of clinical applications 196–198 . Regev‐Rudzki N et al 194 .…”

“… 193 , 194 , 195 Exosomes are products of the paracrine mechanism of stem cells, are more rapidly utilized than stem cells themselves, and have a wide range of clinical applications. 196 , 197 , 198 Regev‐Rudzki N et al. 194 examined the therapeutic effects of MSC‐Exos during fracture healing in a CD9−/− mouse model and found that MSC‐Exos were effective in promoting fracture healing.…”