Rational use of mesenchymal stem cells in the treatment of autism spectrum disorders

Abstract

Autism and autism spectrum disorders (ASD) refer to a range of conditions characterized by impaired social and communication skills and repetitive behaviors caused by different combinations of genetic and environmental influences. Although the pathophysiology underlying ASD is still unclear, recent evidence suggests that immune dysregulation and neuroinflammation play a role in the etiology of ASD. In particular, there is direct evidence supporting a role for maternal immune activation during prenatal life in neurodevelopmental conditions. Currently, the available options of behavioral therapies and pharmacological and supportive nutritional treatments in ASD are only symptomatic. Given the disturbing rise in the incidence of ASD, and the fact that there is no effective pharmacological therapy for ASD, there is an urgent need for new therapeutic options. Mesenchymal stem cells (MSCs) possess immunomodulatory properties that make them relevant to several diseases associated with inflammation and tissue damage. The paracrine regenerative mechanisms of MSCs are also suggested to be therapeutically beneficial for ASD. Thus the underlying pathology in ASD, including immune system dysregulation and inflammation, represent potential targets for MSC therapy. This review will focus on immune dysfunction in the pathogenesis of ASD and will further discuss the therapeutic potential for MSCs in mediating ASD-related immunological disorders.

Allogeneic Human Umbilical Cord Mesenchymal Stem Cells for the Treatment of Autism Spectrum Disorder in Children: Safety Profile and Effect on Cytokine Levels

“…In particular, MSCs derived from the Wharton's jelly of umbilical cord tissue (UC-MSCs) may possess greater immune-modulatory activity [34] and proliferative capacity compared with other MSCs [35,36]. The rationale for MSC therapy to treat ASD has been discussed over the past decade [37,38]; our group proposed the use of stem cell therapy to treat ASD in 2007 [39]. Some studies to date have demonstrated the safety of treatment that included MSCs [40]: of note, the results of a study by Sharma et al showed that the majority (96%) of children with ASD treated with bone marrow-derived cells including MSCs showed global improvements including behavior patterns (66%), social relationships (90.6%), and speech, language, and communication (78%) [41].…”

Placental DNA methylation changes and the early prediction of autism in full-term newborns

“…mediate diseases allied to inflammation and tissue damage such as ASD [32,33]. The specific relationship between this gene and the term autism which is predominantly a male disorder remains to be elucidated.…”

Case Report: Autologous Bone Marrow Derived Intrathecal Stem Cell Transplant for Autistic Children - A Report of Four Cases and Literature Review

“…A cascade of events, leading disruption of neuronal maturation and dysfunctional networking through dysfunctional astrocytic neuronal support. A comprehensive review on this topic was recently published by Liu et al (25). More interestingly, neuropathological investigations have recently provided evidence in support of the inflammatory theory, describing perivascular lymphocytic infiltration in the cerebral white, gray matter, and neuronal leptomeninges, this infiltrates were quantitatively accompanied by a corresponding magnitude of astrocytic activation in the affected regions of the brain.…”

“…Indeed, a recent proteomic analysis study discovered nine serum proteins to be significantly different in ASD compared to typically developing boys and a significant correlation with ASD severity according to ADOS (24). Possible mechanisms for the way stem cells improve autism have been discussed more extensively by Liu et al (25). In summary, two mechanisms seem to prevail: (a) reset of the immunological system and (b) improved vascular perfusion of the brain, two mechanisms that are addressed both by the stem cells but also by the bone marrow plasma, rich in growth hormones.…”