The etiology of Autism Spectrum Disorder is linked to both genetic and environmental factors. Environmental factors include perinatal infections, asphyxia, fetal exposure to alcohol and drugs, viral infections, contamination from heavy metals and sensitivity to vaccines. These are the agents that result in brain aggression in the areas involved with the pathology of ASD and may be determining factors in the development of the disorder. Genetic factors, on the other hand, include Rett Syndrome, Fragile-X Syndrome, Angelman Syndrome, epilepsy [2,13-15]. There is no specific treatment for patients affected by this pathology. Today, the literature and clinical treatment are based on cognitive behavioral therapy and drug treatment. Those most commonly cited in the literature are: stimulating the vagus nerve [16,17], Deep Brain Stimulation (DBS) - a technique that has been around since 1960, based on an invasive procedure in which the electrode is placed in the target areas of the brain [18]; dystonia [19]. The discovery of stem cells in 2000 created great interest in their use for regenerative therapy, for a variety of organs and tissues. The progression of various diseases may be checked or even halted through the transplantation of stem cells [20,21]. Consequently, hopes are high, both for the patient who may get individual treatment, customized according to the level of seriousness, and for the parents and family members who have to face difficult choices of treatment and management options for their children. 

The aim of this study was to compile current information on the development and efficacy of using stem cells for patients with autism. However, we cannot ignore the fact that, in connection with publication bias, a possible limitation of the present study must be mentioned. Of the available databases, only PubMed was used as it is the database most frequently accessed and as it provides broad coverage. In fact, when a search is carried out on non-scientific research databases, such as Google, it may result in a broader study, but also in a higher number of false-positives (superfluous studies). Therefore, the articles ultimately selected for review tend to be similar in many situations.

Currently there are two clinical protocols in the international literature regarding the application of stem cells in the treatment of patients with ASD. Firstly, the studies conducted by Yong-Tao Lv and colleagues (2013) investigated the safety and efficacy of the Combined Transplantation of Human Cord Blood Mononuclear Cells (CBMNCs) and Umbilical Cord-Derived Mesenchymal Stem Cells (UCMSCs) in the treatment of children with autism. The experiments were conducted on 37 individuals diagnosed with autism, between the ages of 3 and 12 years. The study compared the therapeutic efficacy of three groups: CBMNC transplantation with rehabilitation therapy; combined CBMNC and UCMSC transplantation with rehabilitation therapy, and rehabilitation therapy on its own. The authors concluded that the transplantation of stem cells was more effective than conventional rehabilitation therapy for improving some of the characteristics of autism. The mechanisms involved in improving autistic symptoms may take place via an increase in perfusion in areas of the brain and/or the regulation of immune dysfunction. This could improve some behavioral symptoms, visual, emotional and intellectual responses, fear or nervousness, non-verbal communication as well as stereotyped behavior and hyperactivity. The administration of cells via intravenous and intrathecal infusions was well accepted, with no immediate or long-term side effects, with just a few cases of mild fever, which were resolved without special medical intervention. With the safety profile of stem-cell transplantation and the efficacy documented in the proof-of-concept study, randomized and controlled studies are required on a wider scale to better define the efficiency of this intervention in the treatment of autism. Given the results for a small number of individuals, the risk/benefit ratio of stem-cell therapy on autistic children has been shown to be favorable. Another important item of information discovered through this study was that the stem cell effect was higher in the younger age groups due to the greater plasticity of the brain and the increased availability of precursor cells in the bone marrow [21]. The study did have a number of limitations: small sample size, absence of randomization and no control group. The significant clinical improvements found in the study cannot be ascribed to standalone multidisciplinary therapy. 

Despite the evidence of the safety of cell therapy, given the studies conducted, it was possible to establish that, as of this point in time, there is a scarcity of publications of studies on human beings. Many studies have focused on understanding how and which gene is altered for autism to occur [22-25]. This is because understanding this mechanism could indeed pave the way for a more individualized and consequently more effective therapy for these patients.

Developmental neurobiology has made enormous strides over the last 25 years, principally through the meticulous analysis of the loss of a single gene and the gain of function in a variety of animal models. The genetic revolution discovered the mechanisms of many essential processes, such as the creation of the vertebrate body plan, and the principles through which the stem cells differentiate into many types of cell. There is still much to be done because it has shown itself to be an area of great promise.