“Stem Cells and Depression. Despite efforts to improve the pharmacological treatment of depression, about one-third of patients with depression do not respond to conventional antidepressant therapy. In recent years, other non-pharmacological therapies have been studied, including the use of mesenchymal stem cell therapies to treat depression.
Stem Cells and Depression
Experimental data support that mesenchymal stem cell therapy could be considered a potential treatment for depression, based on its anti-inflammatory and neurotrophic properties. However, some clinical trials involving the treatment of depression with stem cells are underway, with no published results yet, as expressed in the article published by the World Journal of Psychiatry on September 19, 2021.
INFLAMMATION THAT TRIGGERS DEPRESSION
A colossal research effort has been made in the last 60 years to unravel and understand the neurobiological processes underlying depression. In 1968, Carrol in his article Pituitary-Adrenal Function in Depression expressed the following: ‘Chronic stress modulates the inflammatory process that plays a crucial role in the neurobiological aspects underlying depression. However, this research strategy has not led to the development of antidepressant medications.’
Stem Cells and Depression
Interest in the role of immune and inflammatory mechanisms in depression is a natural consequence of studies on the HPA axis. Since cortisol can modulate these responses. Also, consistent data on the role of psychological stress in the development of depression involve alterations in immune functions, mainly due to chronic inflammatory states.
The link between emotional stress, depression, and inflammation seems to imply evolutionary issues. Several lines of evidence suggest that metabolic, endocrine, and immune responses co-evolved, aiding animal surveillance. This is because animals need to actively seek food, exposing themselves to injuries or predation, and also need to defend themselves against pathogens.
In addition to triggering a fight or flight response, stress is characterized by increases in heart rate, blood pressure, cortisol, and catecholamines. It also activates inflammatory pathways in peripheral blood mononuclear cells. However, when exposure to stress is continuous and unresolved, metabolic and physiological responses are triggered, contributing to the formation of chronic inflammatory states.
STEM CELL-BASED THERAPIES FOR NEUROINFLAMMATORY DISORDERS
Stem cell therapies have become a standard for the treatment of inflammatory processes and neurological disorders, both subacute and chronic. Research has suggested the potential use of adult stem cell therapy for various neurological conditions. Conditions such as multiple sclerosis, autoimmune encephalomyelitis, Alzheimer’s disease, other dementia conditions, Parkinson’s disease, and epilepsy. Most studies emphasize the immunomodulatory nature of adult stem cells. With their therapeutic efficacy related to neurological diseases, particularly triggering anti-inflammatory states.
For example
In epilepsy, convulsive activity can induce proinflammatory molecules, affecting the severity and frequency of seizures. Transplantation of bone marrow mononuclear cells (BMMC) or human umbilical cord blood mononuclear cells. In experimental epilepsy, models induced significant improvements in neurological function.
After a seizure, brain injury induces a highly regulated cascade of biological events. Characterized by the release of cytokines, chemokines, and protectins in the neuronal microenvironment. Which was attenuated by adult stem cell transplantation, and decreased inflammatory states. And promoted tissue repair through cell-cell interactions and paracrine effects. Moreover, some evidence showed that adult stem cells stimulate angiogenesis and endothelial repair through paracrine actions. In Alzheimer’s disease, MSCs have been shown to reduce IL-1, IL-2, TNFa, and IFN-γ in serum. And oxidative stress, demonstrating an anti-inflammatory effect.
Among the most relevant mechanisms of action of stem cells is the release of extracellular vesicles. Carrying soluble factors, microRNAs, and organelles. Initially, the release of extracellular vesicles was thought to be an elimination mechanism. This mechanism would allow cells to eliminate proteins and other unwanted molecules.
Several studies have described the beneficial actions of MSCs by delivering exosomes instead of cells. Therefore, MSCs or exosome transplantation could offer an efficient and safe non-pharmacological therapy for treating neurological conditions.
CLINICAL TRIALS IN DEPRESSED PATIENTS
The results of different experimental studies strongly support the potential therapeutic use of stem cells in the treatment of depression. However, although data from experimental models have shown beneficial effects on depression, there are still gaps to explore. We need more studies to clarify if any type of MSC could be as effective and safe as an antidepressant therapy.
As technology and knowledge involving all aspects of cell-based products continue to develop. The easier it is to identify the best alternative (cells or exosomes). To test as an antidepressant treatment, the lower the costs and the more established the routines become.
I invite you to delve deeper into this fascinating topic by reading our article ‘What Are Stem Cells?'”
