Autism spectrum disorders (ASDs) are heterogeneous complex neurodevelopmental pathologies defined by behavioral symptoms, but which have well-characterized genetic, immunological, and physiological comorbidities. Despite extensive research efforts, there are presently no agreed upon therapeutic approaches for either the core behaviors or the associated comorbidities. In particular, the known autoimmune disorders associated with autism are appealing targets for potential stem cell therapeutics. Of the various stem cell populations, fetal stem cells (FSCs) offer the potent immunoregulatory functions found in primordial mesenchymal stem cells, while exhibiting rapid expansion capacity and recognized plasticity. These properties enhance their potential for clinical use. Furthermore, FSCs are potent and implantable "biopharmacies" capable of delivering trophic signals to the host, which could influence brain development. This study investigated the safety and efficacy of FSC transplantations in treating children diagnosed with ASDs. Subjects were monitored at pre, and then 6 and 12 months following the transplantations, which consisted of two doses of intravenously and subcutaneously administered FSCs. The Autism Treatment Evaluation Checklist (ATEC) test and Aberrant Behavior Checklist (ABC) scores were performed. Laboratory examinations and clinical assessment of adverse effects were performed in order to evaluate treatment safety. No adverse events of significance were observed in ASD children treated with FSCs, including no transmitted infections or immunological complications. Statistically significant differences (p < 0.05) were shown on ATEC/ABC scores for the domains of speech, sociability, sensory, and overall health, as well as reductions in the total scores when compared to pretreatment values. We recognize that the use of FSCs remains controversial for the present. The results of this study, however, warrant additional investigations into the mechanisms of cell therapies for ASDs, while prompting the exploration of FSCs as "biopharmacies" capable of manufacturing the full array of cell-signaling chemistry. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Autism and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders. ASDs are clinically defined by deficits in communication, social skills, and repetitive and/or restrictive interests and behaviours. With the prevalence rates for ASDs rapidly increasing, the need for effective therapies for autism is a priority for biomedical research. Currently available medications do not target the core symptoms, can have markedly adverse side-effects, and are mainly palliative for negative behaviours. The development of molecular and regenerative interventions is progressing rapidly, and medicine holds great expectations for stem cell therapies. Cells could be designed to target the observed molecular mechanisms of ASDs, that is, abnormal neurotransmitter regulation, activated microglia, mitochondrial dysfunction, blood-brain barrier disruptions, and chronic intestinal inflammation. Presently, the paracrine, secretome, and immunomodulatory effects of stem cells would appear to be the likely mechanisms of application for ASD therapeutics. This review will focus on the potential use of the various types of stem cells: embryonic, induced pluripotential, fetal, and adult stem cells as targets for ASD therapeutics.

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.

Fetal stem cell- (FSC-) based therapy is a promising treatment option for many diseases. The differentiation potential of FSCs is greater than that in adult stem cells, and they are more tissue-specific and have lower immunogenicity and better intrinsic homing than embryonic ones. Embryonic stem cells have higher proliferative potential than FSCs but can cause teratomas. Therefore, an evaluation of this potential represents an important biomedical challenge. Since regulation of telomere length (TL) is one mechanism governing cellular proliferation, TL is a useful surrogate marker for cell replicative potential. The prenatal dynamics of TL, however, has never been comprehensively studied. In the present study, dynamics of TL and telomerase activity in the human fetal liver during 5–12 weeks of gestation is examined. Both TL and telomerase activity were positively correlated with week of gestation. For both parameters studied, the trend to increase was evident up to 10th week of gestation. After that, they reached a plateau and remained stable. These findings indicate that telomerase activity remains high during the fetal stage, suggesting high replicative capacity of FSCs and their considerable potential for transplantation therapies. These findings, however, are preliminary only due to small sample size and require further evaluation.

The absence of effective treatment methods for Duchenne muscular dystrophy (DMD) calls for new therapeutic approaches. One of the promising treatment methods for DMD is stem cell therapy. This study demonstrates the impact of fetal stem cells (FSCs) on functional capacity and life quality of DMD patients and the ability of FSCs to prevent DMD-related complications in order to inhibit the disease progression. FSC therapy substantially improves functional capacity, life quality, left ventricular ejection fraction, and forced vital capacity of the lungs of DMD patients; this was confirmed by comparison of neurological, laboratory (aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, and lactate dehydrogenase), and morphofunctional findings (left ventricular ejection fraction and forced vital capacity) in DMD patients before the treatment, and 6 and 12 months after the FSC treatment.

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