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Huntington disease (HD) is an inherited disorder hallmarked by progressive deterioration of specific neurons, followed by movement and cognitive anomalies. Cell therapy approaches in neurodegenerative conditions have concentrated on the replenishment of lost/dying neurons with functional ones. Multipotent mesenchymal stem cells (MSCs) have been represented as a potential remedy for HD. In this study, we evaluated the in vitro and in vivo efficacy of umbilical cord matrix stem cells (UCMSCs) and their paracrine effect against oxidative stress with a specific focus on HD. To this end, UCMSCs were isolated, immunophenotypically characterized by the positive expression of MSC markers, and exhibited multilineage potentiality. Besides, synthesis of neurotrophic factors of GDNF and VEGF by UCMSC was confirmed. Initially, PC12 cells were exposed to superoxide in the presence of conditioned media (CM) collected from UCMSC (UCMSC-CM) and cell viability plus neuritogenesis were measured. Next, bilateral striatal transplantation of UCMSC in 3-nitropropionic acid (3-NP) lesioned rat models was conducted, and 1 month later, post-graft analysis was performed. According to our in vitro results, CM of UCMSC protected PC12 cells against oxidative stress and considerably enhanced cell viability and neurite outgrowth. On the other hand, transplanted UCMSC survived, decreased gliosis, and ameliorated motor coordination and muscle activity, along with an increase in striatal volume as well as in dendritic length of the striatum in HD rats. Collectively, our findings imply that UCMSCs provide an enriched platform by largely their paracrine factors, which downgrades the unfavorable effects of oxidative stress.

Abstract: It has been revealed that skeletal muscle cells have the potential to generate, sense and respond to biomechanical signals and that, mechanical force is one of the important factors influencing proliferation, differentiation, regeneration and homeostasis of skeletal muscle cells and myoblasts. The aim of this study was to illustrate the effect of cyclic uniaxial strain on myogenic differentiation of adipose-derived stem cells (ASCs). This study was designed to investigate this effect within 3 days in 4 groups: control (untreated), chemical, chemical-mechanical and mechanical based on exposure of ASCs to chemical growth factors for 3 days or to mechanical strain just on the 2nd day. Finally, cell orientation, muscle-related gene expression, myosin protein synthesis and the number of myosin-positive cells were examined to estimate the rate of differentiation. By studying the cells before and after exposure to uniaxial strain, it could be observed that by exerting the load, the cells were organized almost perpendicularly to strain direction. Real-time RT-PCR demonstrated that uniaxial strain had a significant effect on up-regulation of muscle-related genes in chemical–mechanical group (P <0.001) as compared to mechanical or chemical groups. Immunocytochemistry confirmed the myosin-positive cells in treated groups and the numbers of these cells were enumerated by flow cytometry. These data suggest that uniaxial cyclic strain could affect ASCs and cause their myogenic differentiation and that the combination of chemical myogenic differentiation factors with mechanical signals promotes differentiation much more than differentiation by chemical myogenic differentiation factors or mechanical signals alone. [Copyright &y& Elsevier]

Background: When the spinal cord is damaged, medical procedures are vital to prevent of improvement of the lesion. Because of poor regeneration ability of central nervous tissue, the most injuries are irreversible. One of encouraging interventions for treatment of spinal cord injury is Schwann cell transplantation. However, isolation of Schwann cell for clinical interventions is complicated approach with low cells yield and purity. Thus, easily accessed sources like Adipose mesenchymal stem cells have been taken notice. Therefore, this study was planned to assess the effect of adipose stromal cell-derived Schwann cell transplantation in functional recovery after lateral hemisection in adult rats. Methods: After isolation, adipose stem cells were differentiated to Schwann cells. The differentiation was verified by immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Then, we loaded the cells into collagen scaffolds with parallel aligned canals and transplanted into rats with 3 mm lesions at T9-T10 level. Motor and sensory improvement were evaluated by open field locomotor scale, narrow beam, and tail flick tests for 60 days. Subsequently, conventional histology and immunohistochemistry were performed. Results: In vitro results revealed that mesenchymal stem cells after differentiation gained Schwann cells morphology and markers. Schwann cell-grafted group had significantly higher locomotor and sensory scores in comparison with the control and scaffold without cell groups. Histological observations showed differentiated cells have the ability to improve axonal regeneration and remyelination. Conclusion: Our study proved that adipose tissue-derived Schwann cells can change the rough environment of damaged spinal cord and support axon regeneration and enhance functional recovery, and possibly be helpful for people suffering from spinal cord injuries. [ABSTRACT FROM AUTHOR]

[Display omitted] • Transplantation of DPSCs improved motor skills and muscle activity in rat brain lesion. • Transplantation of DPSCs prevented the atrophy of the striatum. • Transplantation of DPSCs impeded gliosis and microgliosis in rats. • Transplantation of DPSC downregulated Caspase-3 in brain lesion. • Transplantation of DPSCs decreased the expression of inflammatory cytokines, TNF and IL-1β, at mRNA level. Stem cell-based therapy has recently offered a promising alternative for the remedy of neurodegenerative disorders like Huntington's disease (HD). Herein, we investigated the potential ameliorative effects of implantation of dental pulp stem cells (DPSCs) in 3-nitropropionic acid (3-NP) rat models of HD. In this regard, human DPSCs were isolated, culture-expanded and implanted in rats lesioned with 3-NP. Post-transplantation examinations revealed that DPSCs were able to survive and augment motor skills and muscle activity. Histological analysis showed DPSCs treatment hampered the shrinkage of the striatum along with the inhibition of gliosis and microgliosis in the striatum of 3-NP rat models. We also detected the downregulation of Caspase-3 and pro-inflammatory cytokines such as TNF and IL-1β upon DPSCs grafting. Overall, these findings imply that the grafting of DPSCs could repair motor-skill impairment and induce neurogenesis, probably through the secretion of neurotrophic factors and the modulation of neuroinflammatory response in HD animal models. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that differentiation of stem cells into cardiomyocytes is a complex phenomenon that requires sufficient inducing factors at various time points. Cardiac extracellular matrix (cECM) could provide tissue specific microenvironment and act as an inductive template for efficient cell differentiation. The aim of this study was to investigate the effect of cECM on differentiation of human adipose tissue-derived stem cells (hADSCs) into cardiomyocytes using cECM hydrogel in combination with a cardiac inductive cocktail. hADSCs were cultured on ECM-coated plates with and without inductive cocktail for 3weeks. qRT-PCR and western blot analysis were used to evaluate the expression pattern of special cardiac genes and proteins. When hADSCs were cultured in the presence of cECM cardiac genes including GATA4, HAND1, HAND2, NKX2.5, Troponin I, βMHC, Connexin43 were highly expressed in differentiated cells. Also Connexin43, cTnI and βMHC proteins were expressed as well. We could show that cECM by itself could affect viability, proliferation and differentiation of hADSCs. However, combination of cECM with a cardiac inducing cocktail could improve the results. [ABSTRACT FROM AUTHOR]