Objective We updated a prior systematic review of interventions for children (0–12 years) with autism spectrum disorder (ASD), focusing on recent studies of behavioral interventions. Data sources We searched the MEDLINE® (PubMed®), PsycInfo, and Educational Resources Information Clearinghouse (ERIC) databases as well as the reference lists of included studies and recent systematic reviews. We conducted the search in December 2013. Methods We included comparative studies (with treatment and comparison groups) of behavioral interventions with at least 10 participants with ASD in the update, and made our conclusions based on the cumulative comparative evidence across the original report and update. Two investigators independently screened studies against predetermined inclusion criteria and independently rated the quality of included studies. Results We included 65 unique studies comprising 48 randomized trials and 17 nonrandomized comparative studies (19 good, 39 fair, and 7 poor quality) published since the prior review. The quality of studies improved compared with that reported in the earlier review; however, our assessment of the strength of evidence (SOE), our confidence in the stability of effects of interventions in the face of future research, remains low for many intervention/outcome pairs. Early intervention based on high-intensity applied behavior analysis over extended timeframes was associated with improvement in cognitive functioning and language skills (moderate SOE for improvements in both outcomes) relative to community controls in some groups of young children. The magnitude of these effects varied across studies, potentially reflecting poorly understood modifying characteristics related to subgroups of children. Early intensive parent training programs modified parenting behaviors during interactions; however, data were more limited about their ability to improve developmental skills beyond language gains for some children (low SOE for positive effects on language). Social skills interventions varied in scope and intensity and showed some positive effects on social behaviors for older children in small studies (low SOE for positive effects on social skills). Studies of play/interaction-based approaches reported that joint attention interventions may demonstrate positive outcomes in preschool-age children with ASD when targeting joint attention skills (moderate SOE); data on the effects of such interventions in other areas were limited (low SOE for positive effects on play skills, language, social skills). Studies examining the effects of cognitive behavioral therapy on anxiety reported positive results in older children with IQs ≥70 (high SOE for improvements in anxiety in this population). Smaller short-term studies of other interventions reported some improvements in areas such as sleep and communication, but data were too sparse to assess their overall effectiveness. Conclusions A growing evidence base suggests that behavioral interventions can be associated with positive outcomes for children with ASD. Despite improvements in the quality of the included literature, a need remains for studies of interventions across settings and continued improvements in methodologic rigor. Substantial scientific advances are needed to enhance our understanding of which interventions are most effective for specific children with ASD and to isolate elements or components of interventions most associated with effects.

Therapies for Children With Autism Spectrum Disorder: Behavioral Interventions Update

Exosomes deliver functional proteins and genetic materials to neighboring cells, and have potential applications for tissue regeneration. One possible mechanism of exosome-promoted tissue regeneration is through the delivery of microRNA (miRNA). In this study, we hypothesized that exosomes derived from neuronal progenitor cells contain miRNAs that promote neuronal differentiation. We treated mesenchymal stem cells (MSCs) daily with exosomes derived from PC12 cells, a neuronal cell line, for 1 week. After the treatment with PC12-derived exosomes, MSCs developed neuron-like morphology, and gene and protein expressions of neuronal markers were upregulated. Microarray analysis showed that the expression of miR-125b, which is known to play a role in neuronal differentiation of stem cells, was much higher in PC12-derived exosomes than in exosomes from B16-F10 melanoma cells. These results suggest that the delivery of miRNAs contained in PC12-derived exosomes is a possible mechanism explaining the neuronal differentiation of MSC.

/pdf/neuronal-differentiation-of-human-mesenchymal-stem-cells-40vo8er57m.pdf

Neuronal Differentiation of Human Mesenchymal Stem Cells Using Exosomes Derived from Differentiating Neuronal Cells

https://journals.sagepub.com/doi/pdf/10.3727/096368914X678427

Spinal cord regeneration.

Cellular therapy is an emerging therapeutic modality with a great potential for the treatment of autism. Recent findings show that the major underlying pathogenetic mechanisms of autism are hypoperfusion and immune alterations in the brain. So conceptually, cellular therapy which facilitates counteractive processes of improving perfusion by angiogenesis and balancing inflammation by immune regulation would exhibit beneficial clinical effects in patients with autism. This is an open label proof of concept study of autologous bone marrow mononuclear cells (BMMNCs) intrathecal transplantation in 32 patients with autism followed by multidisciplinary therapies. All patients were followed up for 26 months (mean 12.7). Outcome measures used were ISAA, CGI, and FIM/Wee-FIM scales. Positron Emission Tomography-Computed Tomography (PET-CT) scan recorded objective changes. Out of 32 patients, a total of 29 (91%) patients improved on total ISAA scores and 20 patients (62%) showed decreased severity on CGI-I. The difference between pre- and postscores was statistically significant (P < 0.001) on Wilcoxon matched-pairs signed rank test. On CGI-II 96% of patients showed global improvement. The efficacy was measured on CGI-III efficacy index. Few adverse events including seizures in three patients were controlled with medications. The encouraging results of this leading clinical study provide future directions for application of cellular therapy in autism.

/pdf/autologous-bone-marrow-mononuclear-cell-therapy-for-autism-4pw9lozqgb.pdf

Autologous Bone Marrow Mononuclear Cell Therapy for Autism: An Open Label Proof of Concept Study

Cell therapy has been identified as an effective method to regenerate damaged tissue Adult stem cells, also known as somatic stem cells or resident stem cells, are a rare population of undifferentiated cells, located within a differentiated organ, in a specialized structure, called a niche, which maintains the microenvironments that regulate the growth and development of adult stem cells The adult stem cells are self-renewing, clonogenic, and multipotent in nature, and their main role is to maintain the tissue homeostasis They can be activated to proliferate and differentiate into the required type of cells, upon the loss of cells or injury to the tissue Adult stem cells have been identified in many tissues including blood, intestine, skin, muscle, brain, and heart Extensive preclinical and clinical studies have demonstrated the structural and functional regeneration capabilities of these adult stem cells, such as bone marrow-derived mononuclear cells, hematopoietic stem cells, mesenchymal stromal/stem cells, resident adult stem cells, induced pluripotent stem cells, and umbilical cord stem cells In this review, we focus on the human therapies, utilizing adult stem cells for their regenerative capabilities in the treatment of cardiac, brain, pancreatic, and eye disorders

Adult Stem Cells for Regenerative Therapy

Administration of autologous bone marrow-derived mononuclear cells in children with incurable neurological disorders and injury is safe and improves their quality of life.

A clinical study shows safety and efficacy of autologous bone marrow mononuclear cell therapy to improve quality of life in muscular dystrophy patients.

Spinal cord injury (SCI) at an early age can be debilitating for the child's growth. Current treatments show a level of stagnancy, after which the recovery is minimal. Cellular therapy is an emerging area of research and has been found to possess many benefits in the previous studies. Transplantation of autologous bone marrow mononuclear cells (BMMNCs) has demonstrated therapeutic potential for many neurological conditions, including spinal cord injury. Here we report a case of 6-year-old girl with traumatic SCI at the level of C7-D1 4 years back, who underwent 2 doses of cell transplantation with autologous BMMNCs with an interval of 6 months along with standard rehabilitation. The patient did not have any major or minor side effects. The patient showed clinical improvements throughout the 6 months after transplantation, which was assessed using Functional Independence Measure (before: 82, after: 101 out of 126). There were patchy areas of sensory gain in bilateral feet recorded, with improvements in the bladder sensation and control. Improved gait was seen as a result of better strength in abdominals and back extensors. The fact that there was functional improvement in the chronic plateau phase indicates the potential of cell therapy in chronic SCI. Further clinical studies are warranted.

https://downloads.hindawi.com/journals/cris/2014/404207.pdf

Functional Recovery in Chronic Stage of Spinal Cord Injury by Neurorestorative Approach: A Case Report

Multiple sclerosis (MS) is widely believed to be an autoimmune disorder characterized by multifocal lesions of the central nervous system (CNS) myelin and accumulating clinical signs due to axonal damage. Persistent loss of myelin can make axons more vulnerable to repeated injury, induce axons to make compensatory changes in their properties that can result in further delayed insults to the axon. Autologous hematopoetic stem cell transplantation (HSCT) has been used as a treatment for MS. Stem cells have the ability to greatly assist in regenerating the damaged glial cells. We present herein a case of a patient who underwent transplant twice to improve his disability.

Administration of Autologous Bone Marrow Stem Cells Intrathecally in Multiple Sclerosis Patients is Safe and Improves their Quality-of-life

Common causes of anterior horn cell disease are poliomyelitis, motor neuron disease and spinal muscular atrophy. The primary pathology is the progressive loss of anterior horn cells. We presents a 29 year old female suffering from the motor neuron disease with anterior horn cell involvement since the last five years. She had exhausted all treatment options so was given intrathecal autologous bone marrow derived stem cell therapy as part of the neuror egenerative rehabilitation therapy protocol at our centre. The patient showed functional as well as neurological improvements after receiving the therapy. A detailed case report is presented herewith.

V. C. Jacob

Papers

Administration of autologous bone marrow-derived mononuclear cells in children with incurable neurological disorders and injury is safe and improves their quality of life.

A clinical study shows safety and efficacy of autologous bone marrow mononuclear cell therapy to improve quality of life in muscular dystrophy patients.

Functional Recovery in Chronic Stage of Spinal Cord Injury by Neurorestorative Approach: A Case Report

Administration of Autologous Bone Marrow Stem Cells Intrathecally in Multiple Sclerosis Patients is Safe and Improves their Quality-of-life

Autologous Bone M arrow Derived Stem Cells for M otor Neuron Disease with Anterior Horn Cell Involvem ent