Mesenchymal stem cells in treating autism: Novel insights

Abstract

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.

Embryonic stem cell transplants as a therapeutic strategy in a rodent model of autism

“…Indeed, two small open-label studies have shown symptom improvement in autistic people treated with MSCs [76,77]. However, problems still exist with this highly controversial cell-based therapy [78] and the mechanisms of action of MSCs has not been completely elucidated.…”

Mesenchymal Stem Cell Transplantation Promotes Neurogenesis and Ameliorates Autism Related Behaviors in BTBR Mice

“…In light of recent clinical studies providing promising evidences for safety and efficacy of MSC transplantation in children suffering from autism, there is a necessity for preclinical models of MSC therapy for ASD to elucidate the restorative mechanisms involved in the beneficial outcome (Siniscalco et al, ). In this work, we demonstrated the potential of MSC treatment in an animal model for ASD and provided novel data relevant to the possible mechanisms in which MSC transplantation may act to trigger brain changes that could restore normal behavioral phenotype.…”

“…Stem cell based regenerative therapy was proposed for the treatment of ASD (Ichim et al, ) as studies have shown that cell transplantation may affect molecular mechanisms associated with ASD pathophysiology. In light of the above mentioned processes, mesenchymal stem cells (MSC) represent an attractive cell source for regenerative therapy for ASD (Siniscalco, Bradstreet, Sych, & Antonucci, ), as studies have shown MSC capacity to improve behavioral endophenotypes of animal models of brain diseases through inducing immunomodulation (Barhum et al, ; Chao, He, & Tay, ; Kassis et al, ; Rafei et al, ; Sheikh et al, ; Stemberger et al, ), enhancing neurogenesis (Bao et al, ; Kan, Barhum, Melamed, & Offen, ; Snyder, Chiu, Prockop, & Chan, ; Tfilin et al, ), increasing neurotrophic factor levels (Barzilay et al, ; Sadan et al, ; Sasaki et al, ; Wakabayashi et al, ; Wang et al, ; Zhang et al, ), and improving glutamatergic balance (Bae et al, ; Barzilay et al, ). We have recently shown that MSC transplantation to the cortex (Barzilay et al, ) and to the hippocampus (Barzilay et al, ) protects from deficits in social behavior following repeated treatment with the NMDA antagonist phencyclidine.…”

Rising Interdisciplinary Collaborations Refine Our Understanding of Autisms and Give Hope to More Personalized Solutions

“…They found that children who completed this training have improved facial processing, at both the behavioral and electrophysiological level, suggesting therapeutic validity for this training system [39]. As we gain insight into the molecular basis of autism, though, there are many other avenues of therapy to pursue, including drug [40] and stem cell therapies [41]. These kinds of treatments are advantageous due to their ability to be tailored to each patient and because they target the biological basis of the disease rather than just the symptoms, however more extensive research is required before they can be clinically implemented.…”