نقش کارایی سلول های بنیادی مزانشیمی در درمان بیماری های مزمن نروزی Functional role of mesenchymal stem cells in the treatment of chronic neurodegenerative diseases

Introduction Stem cells have the ability to renew themselves continuously or differentiate into many cell types. In adult life, stem cells have been identified in several tissues where, by the continuous production of new cells, they guarantee physiological conditions and repair mechanisms after injuries or diseases. In many organs, such as the blood, skin or gastrointestinal tract, stem cells extensively work throughout the organism’s entire life, contributing to rapid replacement of dead or worn out cells. Other tissues, in which repair mechanisms are not so efficient, do not easily recover after injuries or extensive degenerative events. This is the case of the central nervous system (CNS), where for a long time it was believed that only microglia, astrocytes, and oligodendrocytes proliferate in the adult organism, whereas neurons were considered unable to divide. Indeed, this limitation has to be partially revised, since it has been demonstrated that in at least two areas of the brain, the dentate gyrus of the hippocampus and the subventricular zone adjacent to the lateral ventricles (SVZ), neural stem cells (NSCs) can continuously generate new functional neurons (Gage, 2002). However, they likely account for neurogenesis only within limited regions of the brain and are not able to counteract diffuse neuronal death as it occurs in neurodegenerative diseases (Lie et al., 2014). In these cases, the gradual and progressive loss of neural cells severely impairs the quality of life of patients, mostly because of cognitive and behavioral dysfunctions. As pharmacological approaches have induced in many instances poor effects, stem cell-based brain transplantation therapies have been extensively investigated (Chan et al., 2014). Different lines of stem cells have been explored (Blundell and Shah, 2015). Embryonic stem cells have been widely studied for their pluripotency and very high proliferative potential. However, they raise ethical/religious issues and involve the risk of easily producing tumors. Induced pluripotent stem cells, reprogrammed from autologous somatic cells could also differentiate to neural cells, but their safe use has not yet been properly assessed. Considering their nature, NSCs would appear the most suitable tool (Kim et al., 2013). In fact, they already give origin to the three main cell types of the mammalian CNS: neurons, astrocytes, and oligodendrocytes. Unfortunately, having to be extracted from the nervous tissue, autologous NSCs are hardly available in sufficient amounts without significant harm for the patient (Chan et al., 2014). In addition, data on NSC transplantation are controversial, since when injected in vivo, they may remain in the undifferentiated form. These cells are also susceptible to immune responses upon allogeneic transplantation (Rossignol et al., 2014).