Mesenchymal stromal/stem cells (MSCs) as non-hematopoietic stem cells are located in the stroma of the bone marrow and make up 0.001–0.01% of the total number of nucleated cells in the bone marrow. Although human MSCs are isolated from adipose tissue, liver, spleen, thymus, umbilical cord blood, placenta, Wharton’s jelly, brain, lungs, dental pulp, palatine tonsils, peripheral blood, and other sources, they are mainly present in the bone marrow. MSCs do not have identical markers, probably due to species diversity, different tissue sources and cultivation conditions. MSCs obtained from different sources are similar in phenotype, but differ in function.
MSCs perform their role in the bone marrow by means of direct cross-cell interactions, as well as the secretion of soluble factors of a wide spectrum of action. MSCs can migrate into damaged tissues and, thanks to their ability to differentiate into various cell lines, as well as due to the secretion of soluble molecules, they can regenerate these damaged tissues. MSCs enhance angiogenesis and inhibit fibrosis by means of angiogenic and antifibrotic factors, respectively.
Exosomes
Due to the endosomal origin of exosomes, they all include membrane-bound proteins such as tetraspanins, MHC-I and MHC-II, heat shock proteins, GTPases and proteins involved in the biogenesis of multivesicular bodies. In addition, metabolic enzymes were identified in exosomes.
Certain protein components depend on the origin of exosomes and may change depending on physiological changes. In addition to proteins, exosomes are enriched with a set of cytokines, some lipid rafts, such as phosphoglycerides, cholesterol, ceramides, fatty acyl chains, as well as mRNA, microRNA, non-coding RNA, tRNA, rRNA, and rarely DNA.
Therapeutic effect of exosomes obtained from MSCs
Mesenchymal stem cells improve the recovery of damaged tissues and also modulate immune reactions.
Thus, the isolation and identification of exosomes from MSC culture media have made them a popular choice for cell-free therapy in research and clinical trials that may have clinical applications in the near future. Intravenous injection of exosomes secreted from human umbilical cord MSCs has a supportive effect on weight loss and does not have a harmful effect on kidney or liver function. These exosomes (MSC-DE) also have anti-apoptotic and anti-inflammatory effects, counteract heart remodeling, heart regeneration, neovascularization and anti-vascular remodeling of the cardiovascular system. MSC-EVs protect cardiac tissue from ischemic damage through angiogenesis-promoting effects. In addition, exosomes obtained from MSCs reduce myocardial ischemia/reperfusion injury in mouse models. Exosomes obtained from BM-MSC protect kidneys from ischemia-reperfusion injury by reducing inflammatory reactions and apoptosis in rats. MicroRNA-enriched exosomes probably play a crucial role in cellular functions such as homeostasis and hematopoiesis.
Researches in recent years show that MSC exosomes can play a key role in the regeneration and repair of damaged tissues, as well as in the modulation of immune responses. Exosomes are capable of carrying various biomolecules, such as microRNAs and proteins, which can regulate the functions of host cells and participate in many physiological and pathological processes. The presented review highlights the potential of exosomes as a tool for the development of new cell-free therapy strategies in a number of clinical applications, including cardioprotection, nephroprotection, as well as in the treatment of neurodegenerative diseases and external skin damage. In conclusion, MSC exosomes open new horizons in cell-free therapy, promising more effective and safe methods of treating various diseases.
