Therapeutic utility of mesenchymal stromal cell (MSC)-based approaches in chronic neurodegeneration: a glimpse into underlying mechanisms, current status, and prospects

Abstract

Recently, mesenchymal stromal cell (MSC)-based therapy has become an appreciated therapeutic approach in the context of neurodegenerative disease therapy. Accordingly, a myriad of studies in animal models and also some clinical trials have evinced the safety, feasibility, and efficacy of MSC transplantation in neurodegenerative conditions, most importantly in Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). The MSC-mediated desired effect is mainly a result of secretion of immunomodulatory factors in association with release of various neurotrophic factors (NTFs), such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF). Thanks to the secretion of protein-degrading molecules, MSC therapy mainly brings about the degradation of pathogenic protein aggregates, which is a typical appearance of chronic neurodegenerative disease. Such molecules, in turn, diminish neuroinflammation and simultaneously enable neuroprotection, thereby alleviating disease pathological symptoms and leading to cognitive and functional recovery. Also, MSC differentiation into neural-like cells in vivo has partially been evidenced. Herein, we focus on the therapeutic merits of MSCs and also their derivative exosome as an innovative cell-free approach in AD, HD, PD, and ALS conditions. Also, we give a brief glimpse into novel approaches to potentiate MSC-induced therapeutic merits in such disorders, most importantly, administration of preconditioned MSCs.

Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles

“…Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been reported to show potent anti-inflammatory effects in a variety of diseases such as osteoarthritis, cardiovascular diseases, graft-versus-host disease (GVHD), and neurodegenerative diseases [ 1 – 5 ]. As nanoscale non-reproducible lipid bilayer particles, EVs are naturally released by most, if not all, types of cells and are present in most bodily fluids [ 6 , 7 ].…”

Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats

“…MSCS can be considered as mini-bioreactors capable of secreting a wide range of cytokines and neurotrophic factors that are crucial in the treatment of neurodegenerative disorders. There is a substantial body of evidence that MSCs express a variety of neurotrophic factors, including nerve growth factor, GDNF, BDNF, insulin-like growth factor-1, and basic fibroblast growth factor at both the mRNA and protein levels [68][69][70]. Synaptic plasticity, as well as the survival and function of midbrain dopamine neurones, are dependent on BDNF.…”

“…8a and b). Neurotrophic factors, such as BDNF and GDNF, are crucial for the synaptic activity, survival, and function of DA neurones, and their decline has been linked to motor deficits associated with aged animals [68][69][70][71][72][73][74][75]. In the striatum of aged rats, the expression of BDNF, GDNF, and VEGF was remarkably reduced when compared with the expression in control rats, and these declines were reversed by BMMSC transplantation (Fig.…”

Anti-aging effect of β-carotene through regulating the KAT7-P15 signaling axis, inflammation and oxidative stress process

“…In addition, we also found that ectopic expression of KAT7 also up-regulated P15, indicating that p15 acts downstream of KAT7 in mediating cellular sensitivity. Of course, the anti-aging mechanism of β-carotene needs further in-depth research in the future, because MSC senescence is a very complex biological process [ 28 – 32 ].…”