Mesenchymal stem cell potential in hormone balancing and depression treatment

People commonly refer to depressive disorders as depression. This condition affects how the mind functions and can completely alter the patient’s perception, behavior, and thoughts. Depression can affect patients of all ages and may manifest as either a persistent or episodic condition. The stages of depression can last for several weeks or throughout one’s lifetime.

Depression and Its Consequences

This depressive condition can significantly impact a patient’s quality of life, potentially leading to its complete deterioration [1, 2]. Depression can plummet an individual from the peak of their career to the lowest societal point. Moreover, depression can strike suddenly without warning signs. It is a prevalent condition worldwide, with approximately 264 million people experiencing depression globally. About 17 million people suffer from depression each year [3]. and the prevalence of severe depressive disorders is twice as high in women as in men. Unfortunately, people often do not take psychological disorders as seriously as physical ailments because they cannot see them with the naked eye. Some of the most common symptoms include low energy and/or fatigue, difficulty concentrating, insomnia or excessive sleep, loss of interest in hobbies and activities, and thoughts of death or suicide [4].

Mechanisms of Depression

Neurotransmitters are chemicals in the brain responsible for transmitting messages between nerve cells. If neurotransmitters do not function normally, your brain may not receive the necessary commands, leading to the development of depression  [5].

Emotional or physical trauma can cause depression in patients. Sad memories can persistently induce depression in patients, and emotional trauma during childhood may lead to later-life depression [6].

The lack or excess of hormones can contribute to depression for various reasons. Postpartum depression is a common phenomenon for new mothers due to the significant hormonal changes during pregnancy. The absence of many hormones present during the gestation period can easily lead to the development of postpartum depression [7]. Some researchers hypothesize that there is a depression gene that patients may inherit from their parents.

Current Treatment Methods

Treatment options for major depressive disorders are quite limited and often do not address underlying issues. Patients usually need to try various medications or treatment methods before finding one that effectively treats their symptoms. Many patients become dependent on medications throughout their lives.

Therapy

One of the most common treatment methods for depression is therapy. Therapy can help some patients gradually alleviate symptoms related to trauma. Patients can overcome their issues and traumas by recognizing problems and changing negative thoughts into positive ones. This treatment method demonstrates its effectiveness in treating depressive patients. Therapy can last for only a few weeks or a lifetime, depending on the individual. Some patients may only need a few sessions to alleviate depression and address their issues.

Medication

If therapy is ineffective, many healthcare professionals will recommend long-term or short-term medication. Antidepressant medications have shown that they can treat depressive symptoms. These medications actually help change the chemicals in the patient’s brain. People typically take antidepressant medications on a daily basis. Pharmaceutical companies released imipramine, a tricyclic antidepressant, and iproniazid, a monoamine oxidase inhibitor, as the first antidepressant medications in 1957 [8]. Despite efforts to improve depression treatment with medication, about one-third of patients do not respond to conventional antidepressant medications. The mechanism of action of the currently available antidepressant medications may explain the limitations of their effectiveness.

Using Stem Cells in Treatment for Depression

Researchers believe that mesenchymal stem cells (MSCs) help maintain optimal brain function. Additionally, these stem cells may contribute to reducing depression [9]. The multi-potential properties of MSCs make them a worthy consideration for developing clinical applications. Stem cells have the ability to generate more nerve cells, leading to increased connectivity in the brain. Some studies have also observed the anti-inflammatory activity of MSCs. While most antidepressant medications act on the monoamine transmission regulation mechanism, many patients still experience residual symptoms, and the remission rate is low.

Stem cells play a fantastic role in reducing inflammation throughout the body. They are also excellent at promoting cell regeneration. Stem cells release anti-inflammatory factors and growth factors wherever they go. This makes stem cells an incredibly attractive option for depressed patients [10]. The hope is that stem cells can improve the condition of the brain and alleviate depressive symptoms. If a patient is depressed due to increased inflammation, stem cells injected into the bloodstream may improve their condition. A small study on mice showed that stem cells could reduce brain inflammation [9]. Researchers injected stem cells into mice, and within three weeks, brain inflammation significantly decreased. A similar therapeutic approach could be used to combat inflammation in depressed patients.

Researchers have also actively discussed directly injecting stem cells into the hippocampus. In older patients, stem cells in the hippocampus are not as robust as those in younger patients. Injecting stem cells is a more effective option and an attractive choice for improving depressive symptoms. Newly injected stem cells may generate new nerve cells in the brain. The underlying issue may be that stem cells in the brain are simply not strong or young enough to repair damage. As patients age, the stem cells in their bodies are not as robust as when they were young. Stem cell pills will be an appealing treatment option for the public as it does not require invasive treatment.

Pre-clinical and Clinical Trials in Depression Treatment

A small molecule derived from stem cells, NSI-189, administered orally, has shown effectiveness in a few patients with major depressive disorder (MDD) [11]. This molecule is the first potential antidepressant that does not act on monoamines but promotes the development of new nerve cells in the hippocampus. To assess the safety and absorption capacity of NSI-189, Dr. Fava and his team selected 24 MDD patients [12]. The patients were randomly assigned in a 3:1 ratio to receive the active drug at one of three doses (40 mg once daily, 40 mg twice daily, or 40 mg three times daily; n = 6 patients each) or placebo (n = 2 patients) for 28 days. During the treatment period, the clinic monitored them and later discharged them, with regular follow-up visits for another 8 weeks.

The researchers found that NSI-189 was well-absorbed, and they did not identify any serious side effects for any of the tested doses. Four measures were used to assess clinical efficacy: the Symptoms of Depression Questionnaire (SDQ), the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impressions-Improvement (CGI-I), and the Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ). Treatment with NSI-189 resulted in a reduction in depressive symptoms and cognitive improvement across all measures, with significant improvement in SDQ and CPFQ, and a moderate to large effect size for all measures.

Results from various experimental studies strongly support the potential use of stem cells in depression treatment. However, while data from experimental models have shown beneficial effects in depression, there are still gaps to be explored. Deeper studies are necessary to clarify whether any type of MSC can be effective and safe as an antidepressant therapy. The first clinical trials involving cell-based products or exosomes for treating depression have been registered on international platforms to address these gaps. The search at Clintrial.gov used keywords such as “depression,” “major depressive disorder,” and “cell therapy.” Currently, four clinical trials (Phase 1 and 2) are being evaluated for the safety, efficacy, and absorption capacity of using MSCs and exosomes (NCT02675556; NCT03522545; NCT03265808; NCT04202770). However, most results are not yet available as these studies are still in the patient recruitment stage.

Mesenchymal Stem Cells Bring Hope for Depression

Recent drug-based depression treatment methods primarily target the monoamine neurotransmitter system. This approach has a slow onset of efficacy, taking weeks to months before clinical improvement. On the other hand, psychopharmacology is undergoing an exciting period. Importantly, when combined with current breakthroughs in gene-editing tools and the use of stem cells, it brings innovative and differentiated options to the disease model and the exploration of depression treatments. In experimental models, different MSCs have shown promising therapeutic capabilities in reversing depression-like behavior. There are still a limited number of pre-clinical studies.

As technology and knowledge related to all aspects of cell or cell-based products develop, determining the best alternative (stem cells or exosomes) for testing as a depression treatment becomes easier, more cost-effective, and better established in the process. Several open questions regarding the effectiveness of using mesenchymal stem cells in depression treatment require assessment through more clinical studies.

References:

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