The Efficacy of Naïve versus Modified Mesenchymal Stem Cells in Improving Muscle Function in Duchenne Muscular Dystrophy: A Systematic Review

Abstract

As one of the most common genetic conditions, Duchenne muscular dystrophy (DMD) is a fatal disease caused by a recessive mutation resulting in muscle weakness in both voluntary and involuntary muscles and, eventually, in death because of cardiovascular failure. Currently, there is no pharmacologically curative treatment of DMD, but there is evidence supporting that mesenchymal stem cells (MSCs) are a novel solution for treating DMD. This systematic review focused on elucidating the therapeutic efficacy of MSCs on the DMD in vivo model. A key issue of previous studies was the material-choice, naïve MSCs or modified MSCs; modified MSCs are activated by culture methods or genetic modification. In summary, MSCs seem to improve pulmonary and cardiac functions and thereby improve survival regardless of them being naïve or modified. The improved function of distal skeletal muscles was observed only with primed MSCs treatment but not naïve MSCs. While MSCs can provide significant benefits to DMD mouse models, there is little to no data on the results in human patients. Due to the limited number of human studies, the differences in study design, and the insufficient understanding of mechanisms of action, more rigorous comparative trials are needed to elucidate which types of MSCs and modifications have optimal therapeutic potential.

Stem Cells in Clinical Trials on Neurological Disorders: Trends in Stem Cells Origins, Indications, and Status of the Clinical Trials

“…Indications that included surprisingly few clinical trials were, for instance, Parkinson’s disease, Alzheimer’s disease, Encephalopathy and Muscle Atrophy/Dystrophy. Common for these groups is a gap between pre-clinical studies with positive results and clinical trials with the shortage of efficacy [ 58 , 59 , 60 , 61 , 62 ].…”

Targeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats

“…Currently, stem cell-based therapies are one of the most important emerging medical fields indifferent pathophysiological conditions and diseases, such as cardio-vascular diseases [ 26 , 27 , 28 ], autoimmune diseases [ 29 , 30 ], hereditary genetic conditions [ 31 ], and cancer [ 32 , 33 ]. Mesenchymal stem cells have attracted an increased attention as cellular vehicles for cancer therapy due to their low immunogenicity, fast ex vivo expansion, and inherent tumor-tropism and migratory properties.…”

Therapeutic Application of Extracellular Vesicles-Capsulated Adeno-Associated Virus Vector via nSMase2/Smpd3, Satellite, and Immune Cells in Duchenne Muscular Dystrophy

“…Finally, vectors can be developed to avoid immune system attacks [81]. In addition, MSCs have been shown to improve pulmonary, cardiac, and distal skeletal muscle functions by their ability to fuse with dystrophic muscle, anti-inflammatory activities, and trophic factors that augment the activity of endogenous repair cells [176,177]. Furthermore, systemic administration of continuous IL-10 expressing MSCs by AAV vector into the CXMDj model indicated improvement of running capacity and recovery of tetanic force [178].…”

“…In addition, AAV vectors administrated in vivo are consumed by innate immunity plasmacytoid dendritic cells, as mediated by Toll-like receptor 9 [205]. Therefore, attempts have been made to suppress these immune responses [81,174,177]. Furthermore, AAV-encapsulating EVs can also be introduced into in vivo barrier tissues such as the brain, eyes, and inner ear [189][190][191][192][193][194][195][196][197][198][199][200].…”