Health care providers’ awareness on medical management of children with autism spectrum disorder: cross-sectional study in Russia

Background: Autism spectrum disorder (ASD) is a complex developmental range of conditions that involves difficulties with social interaction and restricted/repetitive behaviors. Unfortunately, health care providers often experience difficulties in diagnosis and management of individuals with ASD, and may have no knowledge about possible ways to overcome barriers in ASD patient interactions in healthcare settings. At the same time, the provision of appropriate medical services can have positive effects on habilitative progress, functional outcome, life expectancy and quality of life for individuals with ASD. Methods: This online survey research study evaluated the awareness and experience of students/residents (n = 247) and physicians (n = 100) in the medical management of children with ASD. It also gathered the views and experiences of caregivers to children with ASD (n = 158), all based in Russia. Results: We have established that the Russian medical community has limited ASD knowledge among providers, and have suggested possible reasons for this. Based on results from online surveys completed by students/residents, non-psychiatric physicians, and caregivers of children diagnosed with ASD, the main problems pertaining to medical management of individuals with ASD were identified. Possible problem solving solutions within medical practice were proposed. Conclusions: The results from this study should be considered when implementing measures to improve healthcare practices, and when developing models for effective medical management, due to start not only in Russia but also in a number of other countries

Mesenchymal stem cells and the neuronal microenvironment in the area of spinal cord injury

© 2019 Medknow Publications. All rights reserved. Cell-based technologies are used as a therapeutic strategy in spinal cord injury (SCI). Mesenchymal stem cells (MSCs), which secrete various neurotrophic factors and cytokines, have immunomodulatory, anti-apoptotic and anti-inflammatory effects, modulate reactivity/phenotype of astrocytes and the microglia, thereby promoting neuroregeneration seem to be the most promising. The therapeutic effect of MSCs is due to a paracrine mechanism of their action, therefore the survival of MSCs and their secretory phenotype is of particular importance. Nevertheless, these data are not always reported in efficacy studies of MSC therapy in SCI. Here, we provide a review with summaries of preclinical trials data evaluating the efficacy of MSCs in animal models of SCI. Based on the data collected, we have tried (1) to establish the behavior of MSCs after transplantation in SCI with an evaluation of cell survival, migration potential, distribution in the area of injured and intact tissue and possible differentiation; (2) to determine the effects MSCs on neuronal microenvironment and correlate them with the efficacy of functional recovery in SCI; (3) to ascertain the conditions under which MSCs demonstrate their best survival and greatest efficacy

Mesenchymal stem cells and the neuronal microenvironment in the area of spinal cord injury

© 2019 Medknow Publications. All rights reserved. Cell-based technologies are used as a therapeutic strategy in spinal cord injury (SCI). Mesenchymal stem cells (MSCs), which secrete various neurotrophic factors and cytokines, have immunomodulatory, anti-apoptotic and anti-inflammatory effects, modulate reactivity/phenotype of astrocytes and the microglia, thereby promoting neuroregeneration seem to be the most promising. The therapeutic effect of MSCs is due to a paracrine mechanism of their action, therefore the survival of MSCs and their secretory phenotype is of particular importance. Nevertheless, these data are not always reported in efficacy studies of MSC therapy in SCI. Here, we provide a review with summaries of preclinical trials data evaluating the efficacy of MSCs in animal models of SCI. Based on the data collected, we have tried (1) to establish the behavior of MSCs after transplantation in SCI with an evaluation of cell survival, migration potential, distribution in the area of injured and intact tissue and possible differentiation; (2) to determine the effects MSCs on neuronal microenvironment and correlate them with the efficacy of functional recovery in SCI; (3) to ascertain the conditions under which MSCs demonstrate their best survival and greatest efficacy

Improving Culture Conditions, Proliferation, and Migration of Porcine Mesenchymal Stem Cells on Spinal Cord Contusion Injury Model in vitro

Adipose tissue-derived mesenchymal stem cells (AD-MSCs) are promising for cell therapy in spinal cord injury (SCI). The pig is one of the most approximate models of many human diseases, including SCI. In our study, we selected the optimal conditions for the culture of porcine AD-MSCs and developed an in vitro SCI model based on the culture of cells in injured spinal cord extracts (SCE) 3 days and 6 weeks after SCI. We show that Dulbecco's Modified Eagle Medium (DMEM) with 20% serum content, supplemented with a combination of 5 mM L-ascorbate-2-phosphate and nonessential amino acids, stimulated a typical fibroblast-like morphology and high proliferation of porcine AD-MSCs. SCE caused a higher proliferation of porcine AD-MSCs compared with extracts from an intact spinal cord. The optimal proliferating effect was achieved using rostral 3 days SCE, and proliferation was lower in caudal and central SCE. Porcine AD-MSCs migration to the 3 days and 6 weeks SCE was higher than to an intact one and preferred the rostral SCE, avoiding central and caudal SCE. We also studied 13 cytokines contained in SCE but did not observe any definite relationship between some analyte concentrations and a change in the behavior of AD-MSCs

Adipose-Derived Mesenchymal Stem Cell Application Combined With Fibrin Matrix Promotes Structural and Functional Recovery Following Spinal Cord Injury in Rats

The use of stem and progenitor cells to restore damaged organs and tissues, in particular, the central nervous system, is currently considered a most promising therapy in regenerative medicine. At the same time, another approach aimed at stimulating regeneration with the use of stem cells encapsulated into a biopolymer matrix and capable of creating a specific microenvironment for the implanted cells similar to the natural extracellular matrix is under active development. Here, we study effects of the application of adipose-derived mesenchymal stem cells (AD-MSCs) combined with a fibrin matrix on post-traumatic reactions in the spinal cord in rats. The AD-MSC application is found to exert a positive impact on the functional and structural recovery after spinal cord injury (SCI) that has been confirmed by the results of behavioral/electrophysiological and morphometric studies demonstrating reduced area of abnormal cavities and enhanced tissue retention in the site of injury. Immunohistochemical and real-time PCR analyses provide evidence that AD-MSC application decreases the GFAP expression in the area of SCI that might indicate the reduction of astroglial activation. Our results also demonstrate that AD-MSC application contributes to marked upregulation of PDGFβR and HSPA1b mRNA expression and decrease of Iba1 expression at the site of the central canal. Thus, the application of AD-MSCs combined with fibrin matrix at the site of SCI during the subacute period can stimulate important mechanisms of nervous tissue regeneration and should be further developed for clinical applications

Influence of Genetically Modified Human Umbilical Cord Blood Mononuclear Cells on the Expression of Schwann Cell Molecular Determinants in Spinal Cord Injury

Spinal cord injury (SCI) unavoidably results in death of not only neurons but also glial cells. In particular, the death of oligodendrocytes leads to impaired nerve impulse conduction in intact axons. However, after SCI, the Schwann cells (SCs) are capable of migrating towards an area of injury and participating in the formation of functional myelin. In addition to SCI, cell-based therapy can influence the migration of SCs and the expression of their molecular determinants. In a number of cases, it can be explained by the ability of implanted cells to secrete neurotrophic factors (NTFs). Genetically modified stem and progenitor cells overexpressing NTFs have recently attracted special attention of researchers and are most promising for the purposes of regenerative medicine. Therefore, we have studied the effect of genetically modified human umbilical cord blood mononuclear cells on the expression of SC molecular determinants in SCI

Influence of Genetically Modified Human Umbilical Cord Blood Mononuclear Cells on the Expression of Schwann Cell Molecular Determinants in Spinal Cord Injury

Spinal cord injury (SCI) unavoidably results in death of not only neurons but also glial cells. In particular, the death of oligodendrocytes leads to impaired nerve impulse conduction in intact axons. However, after SCI, the Schwann cells (SCs) are capable of migrating towards an area of injury and participating in the formation of functional myelin. In addition to SCI, cell-based therapy can influence the migration of SCs and the expression of their molecular determinants. In a number of cases, it can be explained by the ability of implanted cells to secrete neurotrophic factors (NTFs). Genetically modified stem and progenitor cells overexpressing NTFs have recently attracted special attention of researchers and are most promising for the purposes of regenerative medicine. Therefore, we have studied the effect of genetically modified human umbilical cord blood mononuclear cells on the expression of SC molecular determinants in SCI

Electrophysiological, Morphological, and Ultrastructural Features of the Injured Spinal Cord Tissue after Transplantation of Human Umbilical Cord Blood Mononuclear Cells Genetically Modified with the VEGF and GDNF Genes

In this study, we examined the efficacy of human umbilical cord blood mononuclear cells (hUCB-MCs), genetically modified with the VEGF and GDNF genes using adenoviral vectors, on posttraumatic regeneration after transplantation into the site of spinal cord injury (SCI) in rats. Thirty days after SCI, followed by transplantation of nontransduced hUCB-MCs, we observed an improvement in H (latency period, LP) and M(Amax) waves, compared to the group without therapy after SCI. For genetically modified hUCB-MCs, there was improvement in Amax of M wave and LP of both the M and H waves. The ratio between Amax of the H and M waves (Hmax/Mmax) demonstrated that transplantation into the area of SCI of genetically modified hUCB-MCs was more effective than nontransduced hUCB-MCs. Spared tissue and myelinated fibers were increased at day 30 after SCI and transplantation of hUCB-MCs in the lateral and ventral funiculi 2.5 mm from the lesion epicenter. Transplantation of hUCB-MCs genetically modified with the VEGF and GNDF genes significantly increased the number of spared myelinated fibers (22-fold, P>0.01) in the main corticospinal tract compared to the nontransduced ones. HNA+ cells with the morphology of phagocytes and microglia-like cells were found as compact clusters or cell bridges within the traumatic cavities that were lined by GFAP+ host astrocytes. Our results show that hUCB-MCs transplanted into the site of SCI improved regeneration and that hUCB-MCs genetically modified with the VEGF and GNDF genes were more effective than nontransduced hUCB-MCs

Construction of recombinant adenovirus containing picorna-viral 2A-peptide sequence for the co-expression of neuro-protective growth factors in human umbilical cord blood cells

Several neuro-degenerative disorders such as Alzheimer’s dementia, Parkinson’s disease and amyotrophic lateral sclerosis (ALS) are associated with genetic mutations, and replacing or disrupting defective sequences might offer therapeutic benefits. Single gene delivery has so far failed to achieve significant clinical improvements in humans, leading to the advent of co-expression of multiple therapeutic genes. Co-transfection using two or more individual constructs might inadvertently result in disproportionate delivery of the products into the cells. To prevent this, and in order to rule out interference among the many promoters with varying strength, expressing multiple proteins in equimolar amounts can be achieved by linking open reading frames under the control of only one promoter. Here we describe a strategy for adeno-viral co-expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) interconnected through picorna-viral 2A-amino-acid sequence in transfected human umbilical cord blood mono-nuclear cells (hUCB-Mcs). Presence of both growth factors, as well as absence of immune response to 2A-antigen, was demonstrated after 28–52 days. Following injection of hUCB-MCs into ALS transgenic mice, co-expression of VEGF and FGF2, as well as viable xeno-transplanted cells, were observed in the spinal cord after 1 month. These results suggest that recombinant adeno-virus containing 2A-sequences could serve as a promising alternative in regenerative medicine for the delivery of therapeutic molecules to treat neurodegenerative diseases, such as ALS