First generation stem cell transplants have not as yet produced the reliably improved regeneration that was hoped for, but they do suppress chronic inflammation for some months. This effect is mediated by cell signaling on the part of the transplanted cells in the short time that they survive after transplantation. Much of that signaling is carried by exosomes and other classes of extracellular vesicle, and hence similar outcomes result from therapies based on delivery of exosomes harvested from cultured stem cells.
One of the effects of the unresolved inflammatory signaling characteristic of aging is a suppression of stem cell activity, such as in the cell populations responsible for producing new neurons in the brain. Neurogenesis is essential to brain maintenance, as well as memory and learning. From what is known to date, greater neurogenesis appears to be beneficial at any age. Thus one of the ways in which first generation stem cell and exosome therapies might act to improve cognitive function in older people is via suppression of inflammation leading to improved neurogenesis in the aging brain.
Brain aging is a significant cause of most neurodegenerative diseases and is often irreversible and lacks an effective treatment, leading to a dramatic decline in quality of life. As with other organ systems, brain function gradually declines during the aging, mainly in learning and memory functions. Some studies point out that age-related cognitive decline is characterized by a considerable reduction or even death of neurons in the brain. In the hippocampus (and perhaps in other brain areas), neuronal death can partially compensated by neuronal generation. However, neuronal production is significantly impaired with age. In the adult mammalian hippocampus, new neurons are derived from the stem cell and progenitor cell divisions, a process known as adult neurogenesis.
In recent years, evidence has accumulated that neurogenesis can restore a more youthful state during aging. In addition, increased adult neurogenesis contributes to a variety of human diseases, including cognitive impairment and neurodegenerative diseases. Neuroinflammation has been shown to alter neurogenesis in adults. Various inflammatory components, such as immune cells, cytokines, or chemokines, regulate neural stem cells’ survival, proliferation, and maturation. During normal brain aging, increased inflammatory activity is caused by the activation of glial cells.
It has been shown that mesenchymal stem cells (MSCs) can stimulate neurogenesis and angiogenesis and delay neuronal cell death. At the same time, their secreted exosomes are smaller in size and cause less immune response in the body, which is a hot topic of current research. This manuscript describes how MSCs and their derived exosomes promote brain neurogenesis and thereby delay aging by improving brain inflammation.