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Cell Based Therapy for Duchenne Muscular Dystrophy
No full textMutations in the dystrophin gene cause an X-linked genetic disorder: Duchenne muscular dystrophy (DMD). Stem cell therapy is an attractive method to treat DMD because a small number of cells are required to obtain a therapeutic effect. Here, we discussed about multiple types of myogenic stem cells and their possible use to treat DMD. The identification of a stem cell population providing efficient muscle regeneration is critical for the progression of cell therapy for DMD. We speculated that the most promising possibility for the treatment of DMD is a combination of different approaches, such as gene and stem cell therapy
Clinical Applications of Mesenchymal Stem Cells in Chronic Diseases
Get PDFExtraordinary progress in understanding several key features of stem cells has been made in the last ten years, including definition of the niche, and identification of signals regulating mobilization and homing as well as partial understanding of the mechanisms controlling self-renewal, commitment, and differentiation. This progress produced invaluable tools for the development of rational cell therapy protocols that have yielded positive results in preclinical models of genetic and acquired diseases and, in several cases, have entered clinical experimentation with positive outcome. Adult mesenchymal stem cells (MSCs) are nonhematopoietic cells with multilineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. It is obvious that much work remains to be done to increase our knowledge of the mechanisms regulating development, homeostasis, and tissue repair and thus to provide new tools to implement the efficacy of cell therapy trials
Muscle Cell Sheet-polymer Film generation and Transplantation for the Treatment of Muscular Dystrophy
No full textProliferation and Clonal Characterization of Human muscle Derived CD 133+ stem cell Define an Heterogeneity
No full textHuman Fetal CD133+ Muscle Cells Expressing Perycite Markers Repair Dystrophic Muscle Tissue.
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Identification of miRNAs to improve myogenic differentiation of Mesenchymal Stem Cells as regenerative therapy for Duchenne muscular dystrophy
No full textDuchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy caused by mutations in the dystrophin gene. The absence of the protein caused fibrotic tissue deposition and adipose infiltration into the muscle until complete replacement of original tissue at later stages of the disease and DMD patients die from heart and respiratory failure. Unravelling the precise cellular origin and molecular mechanism of fibrotic and adipogenic tissue within a degenerating human DMD muscle is crucial to understand if the dystrophic muscle environment could influence the outcome of stem cells based therapy and to improve future treatments. Recently, we isolated through FACS sorting from dissociated muscular biopsies two MSC populations that express or not the CD133 antigen. These populations could be responsible for muscle regeneration exhaustion and adipogenic tissue deposition in DMD. We identified miRNAs involved in in-vitro differentiation process and in DMD muscle degeneration in the isolated CD133+ and CD133- hmMSCs and unravelled gene regulatory networks that miRNAs control in DMD. In a clinical prospective, we also tested the therapeutic value of targeting miRNAs to enhance transduction efficiency of hmMSCs into muscle using a dystrophic animal model (scid-mdx mice)
Development of New technologies Inducing Myogenic Differentiation of Human Circulating CD133+ Cells
No full textCombining multiple therapeutic strategies for Friedreich’s ataxia (FRDA): antioxidant metallic nanoclusters as coadjuvants for gene and stem cell therapy
No full textIntroduction FRDA pathology is caused by guanine–adenine–adenine trinucleotide repeat expansion within the first intron of frataxin (FTX) gene, leading to epigenetic silencing. Since mitochondrial FTX controls cellular iron use and redox status maintenance, its lack causes an increased level of reactive oxygen species. We report an effective lentivirus FXN gene delivery to FTX deficient mesenchymal stem cells (MSCs), inducing improvement of neurological functionalities when transplanted in vivo. We also identify antioxidant nanoclusters (NCs) able to block ROS–dependent apoptotic pathways in the FRDA pathology. Methods MSCs from FRDA patient bone marrows were transduced with a lentiviral vector for FXN expression. After LV transduced MSC characterization by FACS, IF, and WB analyses, engineered cells were systemically injected in Fxntm1MknTg (FXN)YG8Pook/2J mice. Behaviour tests (rotarod and treadmill) were performed. Brain tissues were harvested for IF staining and WB. FRDA MSCs labelled with AuAg NCs were characterized to evaluate mitochondrial ROS scavenger activity. Results After LV transduction, MSCs showed the preservation of mesenchymal marker expression (CD73, CD44, CD90 and CD105), colony forming abilities, and capacity to differentiate into multilineages. Comparison with untreated animals revealed i) in vivo FTX rescue; ii) increased number of cerebellar cells expressing Tuj1 neuronal marker; and iii) improvement trend of motor skills in mice injected with engineered MSCs. In addiction, AuAg NCs entered the mitochondria of FRDA MSCs where they reduce ROS levels lowering cell sensitivity to oxidative stress. Conclusions The results confirm the gene and stem cells-based therapeutic applicability to treat the neuronal degeneration in FRDA. The suitability of metallic NCs as anti oxidant agents represents a crucial point as implemental strategy for further ameliorating the progressive ROS mediated degeneration. Indeed, a combined approach based on NCs nasal inhalation in autologous transplanted FRDA patients may be considered as a step further into a clinically relevant treatment
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