Current Trends and Future Outlooks of Dental Stem-Cell-Derived Secretome/Conditioned Medium in Regenerative Medicine

Abstract

Constructing biological substitutes that mimic the structure, architecture, and function of different tissues and organs is the ultimate goal of regenerative medicine. Adult mesenchymal stem/progenitor cells (MSCs) are considered the most widely researched cells in regenerative applications, yet several obstacles that challenge the safe and effective clinical translation of MSC-based therapies still exist. MSCs could partially exert their reparative and regenerative impact through a paracrine effect, mediated by the release of bioactive and trophic factors known as secretome, rather than the actual presence of the engrafted cells in the target site. In addition, MSCs have shown the ability to secrete these various bioactive molecules in their surrounding media (the conditioned media (CM)). MSC-secretome/CM is a set of proteins, lipids, nucleic acids, and trophic factors such as cytokines, chemokines, hormones, growth factors, and extracellular vesicles (EVs). Compared to nondental MSC secretome, dental MSC secretome/CM revealed a higher expression of proliferation-related, metabolic, transcriptional proteins and chemokines, as well as neurotrophins. Dental MSC secretome/CM exhibited experimentally tremendous biological effects, including immunomodulatory, anti-inflammatory, neuroprotective, osteogenic, angiogenic, and antiapoptotic effects, as well as the modulation of oxidative stresses. These aforementioned biological effects greatly explain the increasing interest in dental MSC secretome/CM as an acellular regenerative strategy for the treatment of various clinical diseases/injuries while alleviating the limitations and safety concerns associated with MSC-based therapies.KeywordsCell-free therapyConditioned mediumDental stem cellsExosomesExtracellular vesicles