Depression is considered a serious health disorder especially 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.
Work by scientists, Shwartz and team in Theranostics in 2017 reported that as shown by research, excessive glutamate release has been linked to stress and many neurodegenerative diseases. Flinders Sensitive Line (FSL) – the genetic rat model for depression increased the presence of glutamate and lowered levels of the transporter called glial excitatory amino acid transporter (EAAT) 1. The team made MSCs express EAAT that were administered into FSL rats and tracked using gold nanoparticles. The depression-like symptoms were diminished by the cells as observed by tests and the effects were seen up to 1-month post-transplantation.
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.
Shwartz, A., Betzer, O., Kronfeld, N., Kazimirsky, G., Cazacu, S., Finniss, S., Lee, H. K., Motiei, M., Dagan, S. Y., Popovtzer, R., Brodie, C., & Yadid, G. (2017). Therapeutic Effect of Astroglia-like Mesenchymal Stem Cells Expressing Glutamate Transporter in a Genetic Rat Model of Depression. Theranostics, 7(10), 2690–2703.
Kin K, Yasuhara T, Borlongan CV, Date I. Encapsulated stem cells ameliorate depressive-like behavior via growth factor secretion. Brain Circ 2018;4:128-32.