During the past 30 years, there has been a tremendous growth worldwide in the use of biologics for regeneration of tissue. Currently available biologics include platelet rich plasma, platelet rich fibrin, bone marrow aspirate, lipoaspirate, amniotic derived products and exosomes.
The efficacy of these products is due to the synergy of stem cells, growth factors, cytokines and other bioactive substances such as exosomes.
The clinical application of stem cells in regenerative medicine has been substantially investigated. These cells are readily available by bone marrow aspirate and lipoaspirate. Stem cells migrate to the site of injury and exert their therapeutic effect by interaction with other cells in the area to repair and rejuvenate the tissues.
However, stem cells although once thought to be the epitome of regenerative treatments, have several disadvantages.
Stem cells can have genetic instability and contain chromosomal aberrations. Intravenous administration has been found in some cases to trap cells into the lung microvasculature. Stem cells has been rejected by the host and found to cause tumorigenicity.
Stem cells, in recent studies, may exhibit their ability to regenerate not by differentiation but by their secretion of bioactive molecules such as growth factors, cytokines and exosomes. This secretion and subsequent interaction lead to a cascade of pathways that influence cell division, differentiation and regeneration of tissue. Research into the mechanism of action of cell based treatments such as stem cells, has revealed that intercellular signaling mediates the therapeutic effect. The biologically active molecules generated by the therapeutic cells, either stem cells or non-stem cells, are the actual driving force behind their effect.
The three major types of molecules secreted by the stem cells are growth factors, cytokines and exosomes.
Growth factors are a group of bioactive peptides and proteins secreted by the stem cells and others that when activated induce pathways which initiate migration, proliferation and differentiation.
Cytokines are proteins responsible for the regulation of inflammation, immune response, tissue remodeling and differentiation.
Cytokines and growth factors have overlapped actions and their interaction has immense potential for research in regenerative applications.
Exosomes are secreted by the stem cells and act as paracrine mediators between the stem cell and the target area providing a microenvironment for the damaged tissue.
Exosomes are extremely small. They were once thought to be cellular debris and waste. They are formed from the invagination of the cellular membrane. Exosomes are present in body fluids including the blood plasma and mesenchymal stem cells. In this regard, exosomes derived from stem cells can be used as a therapeutic alternative to stem cells with the same
regenerative qualities. The use of exosomes has a higher safety profile. They have a low immunogenic profile and therefore cannot form tumors. Their extremely small size allows migration to large target organs without getting trapped in the microvasculature.
Considering the benefits of cell free exosomes and the potential disadvantages of whole stem cells therapy, exosomes provide a cell free innovative treatment for clinical applications.
Studies have indicated that mesenchymal stem cells may play a role in tissue repair however these cells demonstrated poor survival and low grafting potential in damaged tissue areas. Further studies have demonstrated that beneficial effects of stem cell applications in repair are attributable to paracrine signaling which includes secreted vesicles such as exosomes. Furthermore, several studies indicate that exosomes secreted by mesenchymal stem cells can replace the MSC therapies in various injury and disease models. Investigations have reveled exosomes secreted by placental umbilical cord MSC play a significant role in wound healing and tissue regeneration.
Exosomes carry intracellular cargo into the extracellar environment. They carry proteins, lipids and the most significant, messenger RNA. It is the RNA that acts as the mediator of cellular communication and a component of various signaling pathways.
Exosomes have a modulatory potential and play a critical role in many diverse biological processes. Exosomes have tremendous therapeutic potential for disorders such as wound healing, neurological damages, cardiovascular dysfunction and musculoskeletal applications. Exosomes are being investigated as drug delivery vehicles to destroy tissue such as cancer.
Juventix Regenerative Medical is an industry leader in the regenerative medical field. We are proud to announce our collaboration with Evolutionary Biologics of New York and offer exosomes and other regenerative biologic products.
Dr. Robert McGrath
Mesenchymal Stem Cell Derived Exosomes: Applications in Regenerative Medicine
Cells 2021 Aug;10(8):1959 PMID 34440728
Current Knowledge and Future Perspectives on Mesenchymal Stem Cell Derived Exosomes as a New Therapeutic Agent
Int J Mol Sci 2020 Jan 22;21(3): 727 PMID 31979113
Cell free Stem Cell Derived Extract Formulation for Regenerative Medicine Applications
Int J Mol Sci 2020 Dec; 21(24): 9364 PMID 33316880
Frontier Review of the Molecular Mechanisms and Current Approaches of Stem Cell Derived Exosomes
Cells 2023 Mar 26;12(7):1018 PMID 37048091