• attention deficit and hyperactivity disorder
• autism spectrum disorder
• c-reactive protein
• inflammation
• procalcitonin

• allogeneic
• autism spectrum disorder
• autologous
• mesenchymal stem cells
• stem cells
•  cellular therapy

• Humans
• Autism Spectrum Disorder/drug therapy
• Stem Cell Transplantation
• Cell- and Tissue-Based Therapy
• Hematopoietic Stem Cell Transplantation

Epidemiological studies have shown that maternal diabetes is associated with autism spectrum disorder development, although the detailed mechanism remains unclear. We have previously found that maternal diabetes induces persistent epigenetic changes and gene suppression in neurons, subsequently triggering autism‐like behavior (ALB). In this study, we investigated the potential role and effect of hematopoietic stem cells (HSCs) on maternal diabetes–mediated gastrointestinal (GI) dysfunction and ALB in a mouse model. We show in vitro that transient hyperglycemia induced persistent epigenetic changes and gene suppression of tight junction proteins. In vivo, maternal diabetes–mediated oxidative stress induced gene suppression and inflammation in both peripheral blood mononuclear cells and intestine epithelial cells, subsequently triggering GI dysfunction with increased intestinal permeability and altered microbiota compositions, as well as suppressed gene expression in neurons and subsequent ALB in offspring; HSC transplantation (HSCT) ameliorates this effect by systematically reversing maternal diabetes–mediated oxidative stress. We conclude that HSCT can ameliorate maternal diabetes–mediated GI symptoms and autism‐like behavior in mouse offspring.

• Autism spectrum disorder
• cannabidiol
• cannabinoids
• endocannabinoid system
• microglia
• neuroinflammation

• Autism spectrum disorders
• Neuro inflammation
• Neurological disorders
• Regenerative medicine
• Stem cell therapy

• Animals
• Autism Spectrum Disorder/genetics
• Autism Spectrum Disorder/therapy
• Autistic Disorder
• Child
• Forecasting
• Humans
• Stem Cell Transplantation

• autism spectrum disorders
• cytokine
• hematopoietic stem cells
• oxidative stress
• superoxide dismutase 2

• Autism spectrum disorder
• Dietary supplementations
• Exclusion diets
• Non-Pharmacological strategies
• Pharmacological interventions
• Stem cell therapies

Autism spectrum disorders (ASDs) are characterized by core domains: persistent deficits in social communication and interaction; restricted, repetitive patterns of behavior, interests, or activities. ASDs comprise heterogeneous and complex neurodevelopmental pathologies with well-defined inflammatory conditions and immune system dysfunction. Due to neurobiologic changes underlying ASD development, cell-based therapies have been proposed and applied to ASDs. Indeed, stem cells show specific immunologic properties, which make them promising candidates in ASD treatment. This comprehensive up-to-date review focuses on ASD cellular/molecular abnormalities, potentially useful stem cell types, animal models, and current clinical trials on the use of stem cells in treating autism. Limitations are also discussed.

• autism spectrum disorder
• cell therapy
• immune dysfunction
• stem cell

• autism
• inflammation
• macrophages
• monocytes
• neuro-immune system

• Children with autism spectrum disorder
• Cytokines
• JAK-STAT signaling
• Peripheral blood mononuclear cells
• Typically developing control children

• Autism
• Biomarkers
• Plasma
• Protein carbonylation
• Redox proteomics

• autism
• autism spectrum disorder
• induced pluripotent stem cells
• stem cells

• autism
• cytokines
• epigenetics
• monocytes
• neuroimmune interactions

Autism spectrum disorders (ASDs) are complex neurodevelopmental disorders characterized by dysfunctions in social interactions, abnormal to absent verbal communication, restricted interests, and repetitive stereotypic verbal and non-verbal behaviors, influencing the ability to relate to and communicate. The core symptoms of ASDs concern the cognitive, emotional, and neurobehavioural domains. The prevalence of autism appears to be increasing at an alarming rate, yet there is a lack of effective and definitive pharmacological options. This has created an increased sense of urgency, and the need to identify novel therapies. Given the growing awareness of immune dysregulation in a significant portion of the autistic population, cell therapies have been proposed and applied to ASDs. In particular, mesenchymal stem cells (MSCs) possess the immunological properties which make them promising candidates in regenerative medicine. MSC therapy may be applicable to several diseases associated with inflammation and tissue damage, where subsequent regeneration and repair is necessary. MSCs could exert a positive effect in ASDs through the following mechanisms: stimulation of repair in the damaged tissue, e.g., inflammatory bowel disease; synthesizing and releasing anti-inflammatory cytokines and survival-promoting growth factors; integrating into existing neural and synaptic network, and restoring plasticity. The paracrine mechanisms of MSCs show interesting potential in ASD treatment. Promising and impressive results have been reported from the few clinical studies published to date, although the exact mechanisms of action of MSCs in ASDs to restore functions are still largely unknown. The potential role of MSCs in mediating ASD recovery is discussed in light of the newest findings from recent clinical studies.

• Autism spectrum disorders
• Autism treatment
• Cell therapy
• Mesenchymal stem cells

Autism and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders characterized by dysfunctions in social interactions, communications, restricted interests, and repetitive stereotypic behaviors. Despite extensive genetic and biological research, significant controversy surrounds our understanding of the specific mechanisms of their pathogenesis. However, accumulating evidence points to the involvement of epigenetic modifications as foundational in creating ASD pathophysiology. Epigenetic modifications or the alteration of DNA transcription via variations in DNA methylation and histone modifications but without alterations in the DNA sequence, affect gene regulation. These alterations in gene expression, obtained through DNA methylation and/or histone modifications, result from transcriptional regulatory influences of environmental factors, such as nutritional deficiencies, various toxicants, immunological effects, and pharmaceuticals. As such these effects are epigenetic regulators which determine the final biochemistry and physiology of the individual. In contrast to psychopharmacological interventions, bettering our understanding of how these gene-environmental interactions create autistic symptoms should facilitate the development of therapeutic targeting of gene expression for ASD biomedical care.

• Animals
• Child Development Disorders, Pervasive/genetics
• Child Development Disorders, Pervasive/therapy
• Environment
• Epigenesis, Genetic
• Histones/metabolism
• Humans