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Utility of tricalcium phosphate and osteogenic matrix cell sheet constructs for bone defect reconstruction

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World Journal of Stem Cells 2015年第5期7卷 873-882页

作者： Tomoyuki Ueha Manabu Akahane Takamasa Shimizu Yoshinobu Uchihara Yusuke Morita Naoya Nitta akira Kido Yusuke inagaki Kenji Kawate Yasuhito Tanaka Department of Orthopedic Surgery Nara Medical University Department of Public Health Health Management and Policy Nara Medical University Faculty of Medicine Department of Biomedical Engineering Doshisha University Department of Arthroplasty and Regenerative Medicine Nara Medical University

AIM: To determine the effects of transplanting osteogenic matrix cell sheets and beta-tricalcium phosphate(TCP) constructs on bone formation in bone ***: Osteogenic matrix cell sheets were prepared from bone marrow stromal cells(BMSCs), and a porous TCP ceramic was used as a scaffold. Three experimental groups were prepared, comprised of TCP scaffolds(1) seeded with BMSCs;(2) wrapped with osteogenic matrix cell sheets; or(3) both. Constructs were implanted into a femoral defect model in rats and bone growth was evaluated by radiography, histology, biochemistry, and mechanical testing after 8 wk. RESULTS: In bone defects, constructs implanted with cell sheets showed callus formation with segmentalor continuous bone formation at 8 wk, in contrast to TCP seeded with BMSCs, which resulted in bone nonunion. Wrapping TCP constructs with osteogenic matrix cell sheets increased their osteogenic potential and resulting bone formation, compared with conventional bone tissue engineering TCP scaffolds seeded with BMSCs. The compressive stiffness(mean ± SD) values were 225.0 ± 95.7, 30.0 ± 11.5, and 26.3 ± 10.6 MPa for BMSC/TCP/Sheet constructs with continuous bone formation, BMSC/TCP/Sheet constructs with segmental bone formation, and BMSC/TCP constructs, respectively. The compressive stiffness of BMSC/TCP/Sheet constructs with continuous bone formation was significantly higher than those with segmental bone formation and BMSC/TCP ***: This technique is an improvement over current methods, such as TCP substitution, and is useful for hard tissue reconstruction and inducing earlier bone union in defects.

关键词： Bone marrow stromal cells Osteogenesis Bone regeneration Tissue engineering Calcium phosphate

Decision Making in Children with Attention-Deficit/Hyperactivity Disorder

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Open Journal of Pediatrics 2016年第2期6卷 158-162页

作者： akira Yasumura Yoshiyuki Takimoto Eisuke Nakazawa Masumi inagaki Department of Developmental Disorders National Institute of Mental Health National Center of Neurology and Psychiatry Tokyo Japan Department of Neuropsychiatry The University of Tokyo Hospital Tokyo Japan Department of Biomedical Ethics The University of Tokyo Tokyo Japan

Background: Informed consent forms and clinical study participation explanations contain many specialized words including medical terms that are difficult to understand. The difficulty is particularly obvious for children with developmental disorders who show attention or similar problems. This study quantitatively evaluated the decision-making ability of these children using the Wechsler Intelligence Scale for Children-III (WISC-III) as a preliminary study for a multi-faceted investigation that would also use physiological indices. Methods: Participants were 11 children with Attention Deficit/Hyperactivity Disorder (AD/HD). The WISC-III was used for quantitative evaluation of their decision-making ability. Results of intelligence quotients (IQs), group indices, and subtest scores were analyzed. Results: The mean Performance IQ was four points lower than the mean Verbal IQ. The mean score for the Processing Speed index was lower by more than one standard deviation (SD). The mean scores for the Coding and Object Assembly subtests were lower by more than two SDs. Conclusion: The WISC-III results for IQ and group indices suggested the efficacy of auditory explanations. In addition, the subtest results suggested the necessity to pay sufficient attention to risk-benefit weighting in explanations. These findings suggested that the decision-making ability of children with AD/HD could be assessed using the WISC-III.

关键词： Attention-Deficit/Hyperactivity Disorder (AD/HD) Decision Making Informed Consent

Behavioral and Neural Enhancing Effects of a Summer Treatment Program in Children with Attention Deficit Hyperactivity Disorder

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Open Journal of Pediatrics 2016年第1期6卷 91-99页

作者： akira Yasumura Kotaro Yuge Chiyomi Egami Chizuru Anai Akiko Mukasa Yushiro Yamashita Masumi inagaki Department of Developmental Disorders National Institute of Mental Health National Center of Neurology and Psychiatry Tokyo Japan Department of Neuropsychiatry The University of Tokyo Hospital Tokyo Japan Department of Pediatrics and Child Health Kurume University School of Medicine Fukuoka Japan Faculty of Nursing Fukuoka Prefectural University Fukuoka Japan NPO Kurume summer treatment program Fukuoka Japan

Deficiency in executive functioning is a core symptom of attention deficit hyperactivity disorder (ADHD). The brain part responsible for executive functions is the prefrontal cortex (PFC). Although drug-based interventions can improve PFC activity, reports on PFC activity being improved by behavioral treatment are lacking. We evaluated whether a summer treatment program (STP) administering comprehensive behavioral treatment would increase PFC activity in children with ADHD. We examined behavioral and neural changes in 20 children before and after the STP, conducted over a 2-week period. We asked the parents/guardians to complete the Swanson, Nolan, and Pelham IV scale to assess severity of ADHD. The main task evaluating executive control was the reverse Stroop task. To examine changes in physiological indices, we used near-infrared spectroscopy to measure changes in PFC activity. Subjective assessments by parents/guardians indicated that ADHD symptoms improved significantly. There was also significant improvement in the number of correct responses and interference rates in the reverse Stroop task. Furthermore, post-intervention PFC activity was significantly higher. These results suggest that the STP improved inhibitory control in executive function, which is considered as a key symptom of ADHD. The increase in PFC activity further suggests that the STP improves cognition through neural function.

关键词： Attention Deficit Hyperactivity Disorder (ADHD) Inhibitory Control Prefrontal Cortex Behavioral Treatment Reverse Stroop Task Near-Infrared Spectroscopy

Increased osteogenesis with hydroxyapatite constructs combined with serially-passaged bone marrow-derived mesenchymal stem cells

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Stem Cell Discovery 2012年第4期2卷 133-140页

作者： Manabu Akahane Tomoyuki Ueha Takamasa Shimizu Yusuke inagaki akira Kido Tomoaki Imamura Kenji Kawate Yasuhito Tanaka Department of Artificial Joint and Regenerative Medicine Nara Medical University Nara Japan Department of Orthopedic Surgery Nara Medical University Nara Japan Department of Public Health Health Management and Policy Nara Medical University School of Medicine Nara Japan

We have previously reported on both the osteogenic potential of hydroxyapatite (HA) combined with bone marrow-derived mesenchymal stem cells (BMSCs) and a method involving osteogenic matrix cell sheet transplantation of BMSCs. In the present study, we assessed the osteogenic potential of serially-passaged BMSCs, both in vitro and in vivo. We also assessed whether an additional cell-loading technique can regain the osteogenic potential of the constructs combined with serially-passaged BMSCs. The present study revealed that passage (P) 1 cells cultured in osteogenic-induced medium showed strong positive staining for alkaline phosphatase (ALP) and Alizarin Red S, whereas P3 cells showed faint staining for ALP, with no Alizarin Red S staining. Staining of P1, P2 and P3 cells were progressively weaker, indicating that the osteogenic potential of the serially-passaged rat BMSCs is lost after P3 in vitro. The in vivo study showed that little bone formation was observed in the HA constructs seeded with P3 cells, 4 weeks after subcutaneous implantation. However, P3 cell/HA constructs which had increased cell-loading showed abundant bone formation within the pores of the HA construct. ALP and osteocalcin mRNA expression in these constructs was significantly higher than that of constructs with regular cell-seeding. The present study indicates that the osteogenic potential of the constructs with serially-passaged BMSCs is increased by additional cell-loading. This method can be applied to cases requiring hard tissue reconstruction, where BMSCs require serial expansion of cells.

关键词： Osteogenesis Mesenchymal Stem Cells Serial Passaging Hydroxyapatite Tissue Engineering Bone Reconstruction

Neurobehavioral and Hemodynamic Evaluation of Cognitive Shifting in Children with Autism Spectrum Disorder

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Journal of Behavioral and Brain Science 2012年第4期2卷 463-470页

作者： akira Yasumura Naomi Kokubo Hisako Yamamoto Yukiko Yasumura Yusuke Moriguchi Eiji Nakagawa Masumi inagaki Kazuo Hiraki Department of Child Neurology NCNP Hospital Tokyo Japan Department of Children Saitama Jyunshin College Saitama Japan Department of Developmental Disorders National Institute of Mental Health National Center of Neurology and Psychiatry (NCNP) Tokyo Japan Department of School Education Joetsu University of Education Niigata Japan Graduate School of Arts and Sciences The University of Tokyo Tokyo Japan

The restrictive, stereotyped behavior in autism spectrum disorder (ASD) is considered to be related to deficits in execu- tive function. In particular, cognitive shifting in executive function is deeply related to stereotyped behavior in ASD. Previous investigations have clarified that the lateral prefrontal cortex is involved in cognitive shifting when flexible changes in attention were needed. However, a few studies have revealed a direct association between cognitive shifting tasks and lateral prefrontal cortex activity in children with ASD. We examined cognitive shifting in 7- to 12-year-old children with ASD and typically developing children using the dimensional change card sort task. In addition, using near-infrared spectroscopy, we examined prefrontal brain activity in conjunction with cognitive shifting. The autistic children provided fewer correct answers and slower reaction times in the task than typically developing children. Fur- thermore, the autistic children displayed a decline in right lateral prefrontal cortex activity during the task compared with typically developing children. In addition, a negative correlation was observed between the severity of autism and brain activity during the task. These results suggest that the activity and physiological indices used in this study may be useful for identifying the symptoms of ASD and discriminating ASD from other disabilities.

关键词： Autism Spectrum Disorder Executive Function Cognitive Shifting Frontal Lobe Function Near-Infrared Spectroscopy