Mesenchymal Stem Cell Exosomes to Treat Disc Degeneration
First generation stem cell therapies involve sourcing immune privileged cells from sources such as umbilical cord blood, or a patient's own cells from fat tissue or similar, expanding the cells in culture, and then injecting them. Only minimal modifications are permitted to cells prior to transplantation in the US, before it would be classed as a therapy that must go through the IND process with the FDA for specific approval. Outside the US, in the medical tourism market, a range of approaches are undertaken with the goal of altering cultured cell behavior to improve patient outcomes. Unfortunately very little of this is backed by published human trial data.
This class of cell therapy produces little to no engraftment of the transplanted cells. Benefits result from the signals generated by the transplanted cells in the short time before they die. The primary outcome is a reduction in inflammatory signaling, dampening the chronic inflammation associated with aging and disease, with some hope of improved tissue maintenance and regeneration. Beneficial outcomes beyond a reduction in inflammation have proven to be quite unreliable, however.
Given that signaling is the mechanism, and that a sizable fraction of molecular traffic between cells is carried in extracellular vesicles such as exosomes, researchers and clinicians have increasingly focused on harvesting these vesicles as a basis for therapy. It is much easier (and thus cheaper) to store, transport, and use exosomes than to store, transport, and use cells. Based on the evidence to date, the outcomes are broadly similar.
Mechanism of Action of Mesenchymal Stem Cell-Derived Exosomes in the Intervertebral Disc Degeneration Treatment and Bone Repair and Regeneration
Exosomes are bilayered extracellular functional vesicles released by different cells with a diameter ranging between 40-120 nm. Exosomes carry out their functions by fusing with cell membranes or binding membrane proteins of the recipient cells. They contain functional proteins, nucleic acids (mRNA, miRNA, lncRNA, etc.) and lipids, and are carriers of intercellular communication between donor and recipient cells. Exosomes originate from a wide range of sources, and almost all cells can secrete exosomes. The exosomes secreted under normal and pathological conditions are different, even for the same cells.
Currently, exosomes are widely viewed as effective therapeutic components derived from mesenchymal stem cells (MSCs), and the secretion of exosomes is an important way for MSCs to promote the repair of surrounding tissue injuries. There is ongoing research into the benefits of therapy with MSC-Exos for IDD, as well as bone defects and injuries. The core underlying pathophysiologic mechanism of intervertebral disc degeneration (IDD) are abnormalities and a reduced number of nucleus pulposus cells (NPCs). The functional substance in MSC-Exos can regulate the cell metabolism and function by transferring to NPCs, endplate chondrocytes and annulus fibrosus cells, thus inhibiting IDD. Additionally, MSC-Exos also showed great therapeutic potential in terms of repair in bone defects and injuries via promoting osteogenic differentiation and angiogenesis and regulating the immune response, and similar results have been illustrated with respect to its therapeutic and preventive effects against cartilage injuries and osteoporosis.
Furthermore, the application of novel biomaterials such as hydrogels could prolong the duration of exosomes at the bone injury site and maintain the function and stability of intracapsular proteins and miRNA. In order to enable MSCs to play a better role in repairing tissue injury, studies should continue the exploration of new methods to promote the delivery of bioactive substances in exosomes more efficient and novel biomaterials that can maintain the physiological state of MSC-Exos.