Stem cell therapy in autism: recent insights

Neurodevelopmental lifelong pathologies defined by problems with social interaction, communication capacity and presence of repetitive/stereotyped clusters of behavior and interests are grouped under the definition of autism spectrum disorder (ASD). ASD prevalence is still increasing, indicating the need to identify specific biomarkers and novel pharmacotherapies. Neuroinflammation and neuro-immune cross-talk dysregulation are specific hallmarks of ASD, offering the possibility of treating these disorders by stem cell therapy. Indeed, cellular strategies have been postulated, proposed and applied to ASD. However, less is known about the molecular action mechanisms of stem cells. As a possibility, the positive and restorative effects mediated by stem cells could be due to their paracrine activity, by which stem cells produce and release several ameliorative and anti-inflammatory molecules. Among the secreted complex tools, exosomes are sub-organelles, enriched by RNA and proteins, that provide cell-to-cell communication. Exosomes could be the mediators of many stem cell-associated therapeutic activities. This review article describes the potential role of exosomes in alleviating ASD symptoms.

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“…Finally, potential exosome therapy, as is the case for all types of cellular therapy [79], will have to be approved by regulatory institutions.…”

Section: Discussionmentioning

confidence: 99%

Stem Cell-Derived Exosomes in Autism Spectrum Disorder

Alessio

Brigida²,

Peluso

et al. 2020

IJERPH

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“…The potentially high preclinical/clinical relevance of iPSC in the study of cerebral functions and the hope to eventually translate this knowledge into the development of future treatment of clinical conditions [24,25], necessitates the development of protocols that enable to differentiate iPSC into both pyramidal (excitatory) and inhibitory neurons, closely resembling human cortical networks [26][27][28]. One of the final goals of neuroscientists working with iPSC is to use these cells not only for the putative treatment of neurodegenerative disorders such as Parkinson's or Alzheimer's disease but also as a source of cells that may potentially rescue physiological impairments characterizing neurodevelopmental disorders (e.g., ASD, schizophrenia).…”

Section: Ipsc: Origin and Applicationsmentioning

confidence: 99%

Profiling parvalbumin interneurons using iPSC: challenges and perspectives for Autism Spectrum Disorder (ASD)

et al. 2020

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Autism spectrum disorders (ASD) are persistent conditions resulting from disrupted/altered neurodevelopment. ASD multifactorial etiology-and its numerous comorbid conditions-heightens the difficulty in identifying its underlying causes, thus obstructing the development of effective therapies. Increasing evidence from both animal and human studies suggests an altered functioning of the parvalbumin (PV)-expressing inhibitory interneurons as a common and possibly unifying pathway for some forms of ASD. PV-expressing interneurons (short: PVALB neurons) are critically implicated in the regulation of cortical networks' activity. Their particular connectivity patterns, i.e., their preferential targeting of perisomatic regions and axon initial segments of pyramidal cells, as well as their reciprocal connections, enable PVALB neurons to exert a fine-tuned control of, e.g., spike timing, resulting in the generation and modulation of rhythms in the gamma range, which are important for sensory perception and attention. New methodologies such as induced pluripotent stem cells (iPSC) and genome-editing techniques (CRISPR/Cas9) have proven to be valuable tools to get mechanistic insight in neurodevelopmental and/or neurodegenerative and neuropsychiatric diseases. Such technological advances have enabled the generation of PVALB neurons from iPSC. Tagging of these neurons would allow following their fate during the development, from precursor cells to differentiated (and functional) PVALB neurons. Also, it would enable a better understanding of PVALB neuron function, using either iPSC from healthy donors or ASD patients with known mutations in ASD risk genes. In this concept paper, the strategies hopefully leading to a better understanding of PVALB neuron function(s) are briefly discussed. We envision that such an iPSC-based approach combined with emerging (genetic) technologies may offer the opportunity to investigate in detail the role of PVALB neurons and PV during "neurodevelopment ex vivo."

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“…Currently, there are two broad classes of ASD interventions; comprehensive treatment models which are structured programs, and focused intervention practices that only treat narrow behavioral symptoms (Wong et al, 2015). These focused single medication strategies include pharmaceuticals, nutritional supplements/special diets (e.g., melatonin, gluten-free, caseinfree, vitamins, and minerals), and alternative or complementary medicine (e.g., chelation, neurofeedback, hyperbaric oxygen therapy, acupuncture, and stem cell therapy; Wong et al, 2015;Siniscalco et al, 2018;Medavarapu et al, 2019). Psychotropic drugs may also play a role in the management of some behaviors commonly associated with ASD, such as aggression, severe irritability, and hyperactivity.…”

Section: Introductionmentioning

confidence: 99%

Beneficial Use and Potential Effectiveness of Physical Activity in Managing Autism Spectrum Disorder

Sefen

Al-Salmi

Shaikh

et al. 2020

Front. Behav. Neurosci.

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Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by poor social and communication skills. Therapeutic interventions are behavioral and educational-normally delivered as structured programs. Several well-established programs exist and most of them do not incorporate physical activity and exercise as core elements. Deficiencies in motor skills are associated with ASD and physical activity has been shown to reduce maladaptive behaviors with autistics. However, the notion of exercise being employed to manage autism is controversial. Meta-analysis and systematic reviews have concluded that physical activity has positive effects on social skills and behavior in young children and adolescents with autism. Activities such as martial arts have been singled out as being particularly beneficial. Established programs such as TEACCH have been successfully modified, as research trials, to be more physical activity-based and have shown positive results. Studies have also reinforced the importance of the role of parental involvement in delivering programs based on physical activity. There is a paucity of research evidence about the long-term effects of physical activity-based interventions. There is also disparity over the detailed nature of the activities and exercises that compose an effective program. Each person with autism has a highly individualized set of symptoms and characteristics for which highly individualized programs are warranted. This is especially true for physical activity programs.

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Stem cell therapy in autism: recent insights

Cited by 37 publications

References 100 publications

Stem Cell-Derived Exosomes in Autism Spectrum Disorder

Stem Cell-Derived Exosomes in Autism Spectrum Disorder

Profiling parvalbumin interneurons using iPSC: challenges and perspectives for Autism Spectrum Disorder (ASD)

Beneficial Use and Potential Effectiveness of Physical Activity in Managing Autism Spectrum Disorder

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