Obsessive-compulsive disorder
Obsessive-compulsive disorder (OCD) is often characterized by excessive behaviors related to cleanliness, including grooming, which is represented across most animal species. In mice, behaviors such as compulsive grooming and hair removal—similar to behaviors in humans with OCD or trichotillomania—are associated with a specific mutation. Chen et al40 reported that the transplantation of bone marrow stem cells into mice with this mutation (bone marrow–derived microglia specifically home to the brain) rescues their pathological phenotype by repairing native neurons.
The autoimmune, inflammatory, and neurodegenerative changes that are prevalent in OCD may be remedied by stem cell treatment in a fashion described throughout this article.
Other conditions
The Box41-50 describes a possible role for stem cells in the treatment or prevention of several types of substance use disorders.
Box
Stem cells and substance use disorders
Researchers have begun to explore stem cells as a potential treatment for several substance use disorders, including those involving alcohol, cocaine, and opioids, as well as their interactions with cannabinoids.
Alcohol use disorder. In a 2017 study, Israel et al41 gave intra-cerebral injections of mesenchymal stem cells (MSCs) to rats that were bred to have a high alcohol intake. The MSC injections resulted in drastic reductions in the rats’ alcohol consumption. A single intracerebroventricular MSC administration inhibited relapse-like drinking by up to 85% for 40 days.
It is beyond unlikely that direct brain injections would be used to treat alcohol use disorder in humans. To address this problem, researchers aggregated MSCs into smaller spheroid shapes, which reduced their size up to 75% and allowed them to be injected intravenously to reach the brain in a study conducted in rats.42 Within 48 hours of a single treatment, the rats had reduced their intake of alcohol by 90%. The IV administration of antiinflammatory MSCs in human trials will be the next step to verify these results.
Alcohol research using human stem cells is also being conducted as a model system to understand the neural mechanisms of alcohol use disorder.43
Cocaine use disorder. In a grant proposal, Yadid and Popovtzer44 suggested that cocaine addiction affects neurogenesis, especially in the dentate gyrus, ventral tegmental area, nucleus accumbens, and prefrontal cortex; it damages mitochondrial RNA, brain-derived neurotrophic factor (BDNF), glutamate transporter (excitatory amino acid transporter; EAAT), and interleukin-10. MSCs have a predilection to these areas and influence neurogenesis. Currently, there are no FDAapproved medications for the safe and effective treatment of cocaine addiction. MSCs can home to pathological areas in the brain, release growth factors, and serve as cellular delivery tools in various brain disorders. Moreover, restoration of basal glutamate levels via the EAAT has been proposed as a promising target for treating cocaine dependence. Therefore, MSCs differentiated to express EAATs may have a combined long-term effect that can attenuate cocaine craving and relapse.44
Neural stem cells undergo a series of developmental processes before giving rise to newborn neurons, astrocytes, and oligodendrocytes in adult neurogenesis. During the past decade, studies of adult neurogenesis modulated by addictive drugs have highlighted the role of stem cells. These drugs have been shown to regulate the proliferation, differentiation, and survival of adult cells in different manners, which results in the varying consequences of adult neurogenesis.45 Reversal of these influences by healthy stem cells can be a worthy goal to pursue.
Opioid use disorder. Opiate medications cause a loss of newly born neural progenitors in the subgranular zone of the dentate gyrus by either modulating proliferation or interfering with differentiation and maturation.46 Opiates were the first medications shown to negatively impact neurogenesis in the adult mammalian hippocampus.47,48 The restoration of hippocampal function may positively affect the prognosis of a patient who is addicted.
Cannabinoids. Cannabinoids’ influence on the brain and on stem cells is controversial. On one hand, deteriorated neurogenesis results in reduced long-term potentiation in hippocampal formation. These cellular and physiological alterations lead to decreased short-term spatial memory and increased depressionlike behaviors.49 On the other hand, there is emerging evidence that cannabinoids improve neurogenesis and CNS plasticity, at least in the adult mouse.50 Through normalization of immune function, and restoration of the brain and the body, stem cells may assist in better health and in treatment of cannabis use disorder.
Chronic pain is a neuropsychiatric condition that involves the immune system, inflammation, vascularization, trophic changes, and other aspects of the CNS function in addition to peripheral factors and somatic pain generators. Treatment of painful conditions with the aid of stem cells represents a large and ever-developing field that lies outside of the scope of this article.51
Experimental, but promising
It is not easy to accept revolutionary new approaches in medicine. Endless research and due diligence are needed to prove a concept and then to work out specific applications, safeguards, and limitations for any novel treatments. The stem cell terrain is poorly explored, and one needs to be careful when venturing there. Presently, the FDA appropriately sees treatment with stem cells as experimental and investigational, particularly in the mental health arena. Stem cells are not approved for treatment of any specific condition. At the same time, research and clinical practice suggest stem cell treatment may someday play a more prominent role in health care. Undoubtedly, psychiatry will eventually benefit from the knowledge and application of stem cell research and practice.
Related Resources
- De Los Angeles A, Fernando MB, Hall NAL, et al. Induced pluripotent stem cells in psychiatry: an overview and critical perspective. Biol Psychiatry. 2021;90(6):362-372.
- Heider J, Vogel S, Volkmer H, et al. Human iPSC-derived glia as a tool for neuropsychiatric research and drug development. Int J Mol Sci. 2021;22(19):10254.
Drug Brand Name
Streptozotocin • Zanosar
Bottom Line
Treatment with stem cell transplantation is experimental and not approved for any medical or psychiatric illness. However, based on our growing understanding of the function of stem cells, and preliminary research conducted mainly in animals, many neurodegenerative-, vascular-, immune-, and inflammation-based psychiatric conditions might be beneficially influenced by stem cell treatment.