We have previously demonstrated that small molecular transfer, such as glucose, between hematopoietic stem cells (HSCs) or mesenchymal stem cells (MSCs) and vascular endothelial cells via gap junctions constitutes an important mechanism of stem cell therapy. Cell metabolites are high-potential small-molecule candidates that can be transferred to small molecules between stem cells and vascular endothelial cells. Here, we investigated the differences in metabolite levels between stem cells (HSCs and MSCs), vascular endothelial cells, and the levels of circulating non-hematopoietic white blood cells (WBCs). The results showed remarkable differences in metabolite concentrations between cells. Significantly higher concentrations of adenosine triphosphate (ATP), guanosine triphosphate (GTP), total adenylate or guanylate levels, glycolytic intermediates, and amino acids were found in HSCs compared with vascular endothelial cells. In contrast, there was no significant difference in the metabolism of MSCs and vascular endothelial cells. From the results of this study, it became clear that HSCs and MSCs differ in their metabolites. That is, metabolites that transfer between stem cells and vascular endothelial cells differ between HSCs and MSCs. HSCs may donate various metabolites, several glycolytic and tricarboxylic acid cycle metabolites, and amino acids to damaged vascular endothelial cells as energy sources and activate the energy metabolism of vascular endothelial cells. In contrast, MSCs and vascular endothelial cells regulate each other under normal conditions. As the existing MSCs cannot ameliorate the dysregulation during insult, exogenous MSCs administered by cell therapy may help restore normal metabolic function in the vascular endothelial cells by taking up excess energy sources from the lumens of blood vessels. Results of this study suggested that the appropriate timing of cell therapy is different between HSCs and MSCs.

Although adult patients with attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) often have sleep problems, few studies have verified the effect of a psychological approach specific to sleep–wake rhythms on these sleep disturbances. Therefore, the aim of this pilot study was to develop a trans-diagnostic approach with sleep scheduling and regularity of sleep duration as core modules, and to examine the effect of the intervention in adult ADHD and/or ASD subjects with sleep disturbances. This was a within-group pilot study. Ten patients with adult ADHD and/or ASD with sleep disturbances (10 males, age: 27.4 ± 5.6 years) took part in a 90-min weekly group intervention for 5 weeks. All participants were assessed on scales for sleep complaints, anxiety, depression, and symptoms of ADHD and ASD before and after the intervention, and at 3-month follow-up. The results showed that the intervention significantly improved sleep disturbances at post-intervention (p = 0.003, d = 1.30, 95% CI 0.31–2.28) and at the 3-month follow-up (p = 0.035, d = 0.41, 95% CI − 0.48 to 1.30). In addition, attention switching for ASD symptoms was significantly reduced post-intervention (p = 0.031, d = 1.16, 95% CI 0.19–2.13). This is the first pilot study of a trans-diagnostic group approach for adult ADHD and/or ASD with sleep disturbances. The intervention primarily led to an improvement of sleep disturbances, followed by improvement of disease-specific symptoms in adult subjects with ADHD and ASD.

The efficacy of hematopoietic stem cell (HSC) therapy for cerebral infarction has been previously demonstrated. However, the lack of response in some patients has hindered its widespread use. To establish HSC therapy as a standard treatment, it is important to examine the causes of non-responsiveness. In this study, we aimed to identify the specifications of transplanted cells based on their therapeutic mechanisms to predict treatment success. We found that HSC therapy activates injured cerebral endothelial cells via gap junctions because cell adhesion between HSCs and the endothelium plays an essential role in cellular communication via gap junctions. The expression of the adhesion molecule integrin β2 (CD18) in CD34-positive (CD34⁺) cells was identified as critical for the therapeutic effect on cerebral infarction in a murine model. Cells with low CD18 expression exhibited a weaker therapeutic effect than cells with high CD18 expression, even when the same number of HSCs was administered. The expression of CD18 in CD34⁺ cells can be used as a specification marker for transplanted HSCs and is useful for identifying non-responders. Furthermore, quantification of CD18 expression is crucial for evaluating the cellular potential of cell-based therapies for diseases where therapeutic effects are mediated through cell adhesion.