Depression is considered a serious health disorder when it is long-lasting. The World Health Organization (WHO) states that across the world, 264 million people suffer from this condition! A person who is affected by depression shows poor performance at their studies or work with relationships also getting impacted. If depression reaches its worst limit-an outcome can be suicide. The WHO states that the annual number of suicides is 800000 people! In fact, it ranks second as a cause of death in people of the age group 15-29 years (WHO fact sheet). While there are treatments available, a challenge for such treatment is a lack of correct diagnosis with people who are depressed not getting diagnosed and those who do not have it are diagnosed incorrectly and also given antidepressants. A research article published in 2016 in Patient preference and adherence reported the side effects of long-term use of antidepressants that include: addiction in 43% patients, emotional numbness in around 65%, weight gain in around 65% and sexual problems in 72% of the users.
The promise of Mesenchymal stem cells (MSCs) has been seen for several neurodegenerative diseases such as Parkinson’s disease and stroke. A 2010 published article in Molecular Psychiatry by Tfilin and team reported that the transplantation of MSCs into rats in the lateral ventricle of the brain showed anti-depressant effects and improved behaviour was seen in the rats. As the effects of healing by stem cells involve the role of many neurotrophic factors secreted by the stem cells, research is currently exploring the use of encapsulated MSCs (eMSCs) that can secrete these factors to hence address depression in animal models.
An article published by Kyohei and team in 2018 in Brain Circulation discussed the use of such eMSCs; when these cells were transplanted in the dentate gyrus (DG) and sub-ventricular zone of the hippocampus, neurogenesis (the formation of neurons from neural stem cells) was observed. This neuron formation was more when encapsulated MSCs were used than MSCs without encapsulation. The specific location where MSCs are transplanted: the lateral ventricle allowed the secretion of various factors that support nerve cell growth such as vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor, fibroblast growth factor-2 and ciliary neurotrophic factor.
The pathways associated with these factors have been shown to mediate antidepressant effects in mice. Hence, the specific transplantation of MSCs in mice that were resistant to depression treatment showed antidepressant effects mainly by neurogenesis and secretion of important factors. The encapsulation of the stem cells helps to increase the time of this secretion. The promise of treating treatment-resistant depression using MSCs is exciting: further studies can help address the long term effects and efficacy to target this serious condition.
WHO fact sheet: https://www.who.int/news-room/fact-sheets/detail/depression
Cartwright C, Gibson K, Read J, Cowan O, Dehar T. Long-term antidepressant use: patient perspectives of benefits and adverse effects. Patient Prefer Adherence. 2016;10:1401–1407. Published 2016 Jul 28. doi:10.2147/PPA.S110632.
Tfilin M, Sudai E, Merenlender A, Gispan I, Yadid G, Turgeman G, et al. Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior. Mol Psychiatry 2010;15:1164-75.
Kin Kyohei, Yasuhara Takao, Borlongan Cesar V, Date Isao (2018) Encapsulated stem cells ameliorate depressive-like behavior via growth factor secretion. Brain Circulation 4 (3): 128-132.