Damian Sendler: Most likely, the discoveries in stem cell research from this century will be remembered for their significance in the understanding of human physiological regeneration, pathological processes involving stem cells, and mechanisms regulating their movement within the body. Our current century is likely to be remembered for these kinds of discoveries. As a huge challenge, there is hope that we will one day find new treatments for a number of diseases that have so far been untreatable, allowing us to live longer and enjoy better quality of life. This is why we are on the lookout for new information on how to correctly identify mental health issues and how to prevent them from occurring in the future. Topics of this special issue on Stem Cells in Neuro-Psychopharmacology and Biomedical Psychiatry include these issues.
Damian Jacob Sendler: There is an introduction to regenerative medicine in this special issue that discusses embryonic and non-embryonic stem cells, as well as their potential applications and current ethical and technical limitations in neurological diseases, including (Ratajczak et al., 2017a). We are still searching for the most efficient stem cell for clinical applications, looking for pluripotent stem cells that have the ability to differentiate into cells from the three germ layers of the human body. Teratomas can form after injection of classical pluripotent stem cells like embryonic stem cells and induced pluripotent stem cells (iPSCs), and both have been shown to have problems with genomic instability in a recent study (Yoshihara et al., 2017). As a result, normal stem cells isolated from adult tissues are the focus of this investigation. However, it remains to be seen if adult tissues contain stem cells with a much broader range of differentiation capabilities.. An additional focus of this paper is to describe how adult stem cells, which are found throughout the body and can be used to repair damaged organs and tissues, can be improved in order to enhance quality-of-life and longevity. These adult stem cells can be found in a variety of organs, including the brain (Ratajczak et al., 2017b). When it comes to stem cells, it is not trivial to say that they can have an impact on the human psyche in a way that is not obvious.
Dr. Sendler: Psychiatric symptoms in fetal alcohol spectrum disorder and epilepsy are examined in the next paper by Dr. Borlongan’s team (Lippert et al., 2017). Intrauterine alcohol exposure harms the developing brain and can lead to brain abnormalities, as is well-known. As a result of the damage done to the developing brain during pregnancy, many children suffer from long-term cognitive, motor, and sensory impairments. Disruptions in neural networks resulting from alcohol abuse are characterised by impaired neurogenesis, which precedes, accompanies and may even worsen psychiatric symptoms, as discussed in greater detail by the authors, In their conclusion, researchers say that stem cell therapies could be used to treat alcohol-related developmental brain disorders in the future.
Damian Sendler
Here, Dr. Samochowiec and coworkers present a summary of their research on the circulation of stem cells in peripheral blood (PB), as well as selected parameters that influence this phenomenon in patients with psychiatric and anxiety disorders. The ability of stem cells to migrate during embryonic development and organogenesis is well-known. The process of stem cell mobilization, which occurs as adults age and their stem cell niches empty, releases a small percentage of hematopoietic stem cells (HSCs), as well as other types of stem cells, such as mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), and even a tiny population of embryonic-like stem cells (VSELs) (Ratajczak 2015). I) systemic or local inflammation, II) strenuous exercise, III) stress, IV) tissue/organ injury, and v) pharmacological agents increase the number of circulating HSCs and other types of non-hematopoietic stem cells in the PB. Furthermore, circulating HSCs and other stem cells have a circadian rhythm in PB, with a peak early in the morning and a nadir late at night, as previously mentioned. Circadian noradrenaline secretion from sympathetic nerve fibers that innervate bone marrow (BM) and changes in the complement cascade (ComC) and coagulation cascade (CoaC) activity due to deep sleep hypoxia control the cyclical circadian release of HSCs (Mendez-Ferrer et al., 2008). (Borkowska et al., 2016).
Stem cell mobilization has been most extensively studied in HSCs. We know that chemokines (e.g. stromal-derived factor 1, SDF-1) and growth factors, as well as bioactive fatty acids (e.g. S1P), extracellular nucleotides, and activation of the ComC and CoaC, all play a role in regulating HSC trafficking in the body, but we do not know much about how this happens. MSCs, EPCs, and VSELs are all examples of non-hematopoietic stem cells that can be trafficked using the same signals (Ratajczak 2015). Circulation may be thought of as the movement of HSCs between different bone marrow stem cell niches in order to maintain a steady supply of BM stem cells in the body. They may also be responsible for keeping an eye out for signs of organ damage or inflammation in the surrounding tissues. HSCs and other types of stem cells in the PB may have similar pro-regenerative effects. Certain psychiatric disorders are associated with an increase in the number of certain types of stem cells circulating in the peripheral blood, as well as factors that regulate their trafficking, such as SDF-1, S1P, and activation of the ComC, according to a study led by Dr. Samochowiec’s group (Kucharska-Mazur et al., 2017). Though postnatal brain neurogenesis and remodeling has been studied for decades, recent findings that show changes in stem cell trafficking in PB allow us to shed new light on the processes of neuroregeneration and neurodegeneration. Psychiatric disorders are entering a new era of research in which therapeutic interventions may have an impact on altered or abnormal brain-regeneration processes. Based on the information gathered thus far, there is reason to be optimistic about finding new indicators of mental illnesses like psychosis or anxiety, and developing stem cell-based therapies to treat those conditions. Psychiatric patients may benefit from the use of stem cells as biomarkers or even as healing factors if further research is done.
Damian Jacob Markiewicz Sendler: A number of psychiatric medications, such as lithium, have been shown to activate stem cells and move them into the PB. Dr. Rybakowski’s team addresses this fascinating topic in the following paper in this special issue (Rybakowski et al. 2017). Stem cell pluripotency and glial cells in the brains of bipolar patients on lithium treatment are summarized in this interesting paper. These are thought-provoking observations, and further research is needed into the possible effects of other psychiatric medications. It would also be interesting to see how treatments such as electro- or insulin-shock therapy affect the movement of these cells into the peripheral blood and the possible enforcement of their movement between the bone marrow and brain.
Damian Jacob Sendler
Neurology and psychiatry are both searching for reliable experimental models to study psychiatric disorders, and this issue is well addressed by Dr. Ulrich’s group in a comprehensive review (Correa-Velloso et al. 2017). Comorbidity between bipolar disorder and Alzheimer’s disease (AD) is discussed in terms of various pathological mechanisms, including aberrant neurogenesis and neurotoxicity. The authors also discuss current therapeutic approaches that have the unfortunate side effect of brain atrophy as a side effect of the treatment of these conditions. Proper comprehension of these intricate mechanisms is necessary for the development of stem cell-based treatments and preventative measures for the progression of BD and Alzheimer’s disease. For this reason, in vitro patient-derived immortalized iPS cells may provide relevant information about the embryonic origins, intracellular signaling pathways, and molecular mechanisms involved in the pathogenesis of these disorders. It is thus possible to better understand the pathogenesis of certain diseases and to develop and test specific drugs by using iPSCs derived from the patient’s own cells.
Damien Sendler: Human iPSC-based tissue-relevant cell types exhibiting an individual’s genetic and molecular background are discussed in greater detail in the second paper from Dr. Ulrich’s group (Liang et al., 2017). Using iPSC technology, the authors describe some major advances in neuroscience and discuss promising futures for personalized medicine in that review. Understanding the cellular and molecular basis of neurological disorders, as well as the discovery of new targets for potential drugs, can be achieved by studying these cells. Advances in disease modeling, treatment evaluation, and cell replacement therapy are expected to be made possible by iPSCs in both neurological and psychiatric disorders as a result of this research.
Finally, Drs. Filipkowski and Kaczmarek’s fascinating paper describes their own findings in cyclin D2 knockout (KO) mice (Filipkowski and Kaczmarek 2017). They were inspired by the findings of others that adult mammals produce new neurons in their brains, and these new neurons may play a pivotal role in learning and memory, mood control, and epileptogenesis (Eriksson et al. 1998). The authors discovered, to their surprise, that cyclin D2-KO mice exhibit only a few phenotypic changes despite having severely impaired adult brain neurogenesis. A number of behavioral paradigms used to assess hippocampal learning and memory in cyclin D2-KO mice showed no significant deficits. As a result, postnatal neurogenesis is questioned in this paper, which offers two alternative explanations for the authors’ findings. To begin, either a compensatory mechanism has yet to be discovered or adult neurogenesis has been greatly exaggerated in the physiology of the brain. Experimentation is needed to solve these difficult problems.
Finally, this is the first time that Progress in Neuro-Psychopharmacology & Biological Psychiatry has published a special issue on stem cells in psychiatry. New and provocative questions posed by the contributors will entice additional researchers to investigate this promising but as yet understudied area of regenerative medicine. This means that new and exciting discoveries are expected in this field in the not-too-distant past.
