According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) published by the American Psychiatric Association, autism spectrum disorders (ASDs) are complex, severe, heterogeneous neurodevelopmental disorders. ASD affects more than 1% of the general population and is characterized by two core symptoms: the first one is impaired social communication, and the second situation is restricted, repetitive types of behavior, interests, or activities. Several biochemical and cellular events are associated with ASDs: oxidative stress, endoplasmic reticulum stress, decreased methylation capacity, limited production of glutathione, mitochondrial dysfunction, intestinal dysbiosis and inflammation, increased toxic metal burden, impaired detoxification, and dysregulation of the brain’s intrinsic immune system (including autoimmunity and activation of neuroglial cells). Despite this extensive body of evidence for an underlying immunotoxicological event in the development of autism, the exact origins of pathogenesis and pathophysiology of ASDs remain to be fully elucidated.
Equally, the presently approved pharmacotherapy fails to address the documented biological aberrations and rather only targets specific behavioral symptoms (i.e., agitation or hyperactivity). Other available treatments for ASDs can be divided into behavioral, nutritional, and biomedical approaches, but a defined standard approach has not been generally accepted. With few well-controlled clinical trials, clinicians are left with the complex challenges of crafting individualized interventions based on limited biomarkers. Novel findings of epigenetic, neuroimmunologic, and environmental changes observed in ASDs suggest that stem cell therapies could be potential interventions for treating autistic syndromes, while enhancing early interventions for autism management in the future.
It is generally agreed that stem cell therapies represent the future of molecular and regenerative medicine for what would otherwise be untreatable human diseases. Stem cells are also suitable for developing cell-based patient-specific pharmacotherapies. Thus, it is hoped that stem cells offer new treatment options for ASDs.
Autism Treatment Option:
Fetal Stem Cells
Fetal stem cells (FSCs) are cells that reside within fetal tissues. Fetal-derived tissues typically contain committed and differentiated cells in addition to the FSCs. These fetal tissues and their associated FSCs divide into 3 subtypes: ectodermal (including brain), mesodermal, and endodermal. These types of cells can cross the blood brain barrier. They have great potential for clinical use as they possess immune-regulatory functions as found in mesenchymal stem cells but exhibit a greater expansion capacity and enhanced plasticity. It has been reported that fetal mesenchymal stem cells exert strong immunomodulatory effects, possess a stable phenotype, and demonstrate less senescence. In addition, unlike ESCs, they are not able to form teratomas (non-cancerous tumors) post transplantation and are obtained from tissues that would otherwise be discarded
Fetal tissue transplantation has become a potential symptomatic treatment and disease management option for patients suffering from neurodegenerative diseases. Cells isolated from first trimester human fetuses have the capacity to survive after transplantation, acquire a mature neuronal phenotype, and mediate a functional effect. FSC benefits could be due to paracrine trophic actions on host tissues (particularly, immune, brain and gastrointestinal tissues), rather than cell replacement. FSCs can produce and release several diffusible neurotrophic and growth factors. Their capacity to suppress proinflammatory cytokines is another key mechanism of action of possible application to ASD therapeutics.
As FSCs are derived from ectodermal, mesodermal, and endodermal layers, they retain their tissue-specific instructions and are therefore regulated properly, unlike pluripotential ESCs. In this way, cell or tissue/organ-specific FSCs could restore dysfunctional development of the brain, gut, and immune system.