We previously reported that in vivo bone formation could be observed in composites of porous hydroxyapatite (HA) scaffolds and cultured mesenchymal stem cells (MSCs). In the present study, we developed a new method for transplantation of cultured MSCs without the necessity of using a scaffold to form bone tissue. MSCs were culture‐expanded and lifted as cell sheet structures. These cell sheets, designated osteogenic matrix sheets, showed positive alkaline phosphatase (ALP) staining, high ALP activities and high osteocalcin (OC) contents, indicating their osteogenic potential. We transplanted these sheets into subcutaneous sites in rats to assess whether they possessed in vivo bone‐forming capability. The transplanted sheets showed mineralized matrix together with osteocytes and an active osteoblast lining, indicating new bone formation, at 6 weeks after transplantation. HA scaffolds were also wrapped with the sheets to make HA/sheet composites and implanted into subcutaneous sites in rats. Histological sections of the composites revealed bone formation in the HA pores at 4 weeks after implantation. Our present results indicate that MSCs can be cultured as sheet structures, and the resulting sheets themselves or HA–sheet composites represent osteogenic implants that can be used for hard tissue reconstruction. Copyright © 2008 John Wiley & Sons, Ltd.

Little is known about the effects of geographic variation on outcomes of out-of-hospital cardiac arrest (OHCA). The present study investigated the relationship between population density, time between emergency call and ambulance arrival, and survival of OHCA, using the All-Japan Utstein-style registry database, coupled with geographic information system (GIS) data.

Introduction: There are inconsistent data about the effectiveness of prehospital physician-staffed advanced cardiac life support (ACLS) on the outcomes of out-of-hospital cardiac arrest (OHCA). Furthermore, the relative importance of bystander-initiated cardiopulmonary resuscitation (BCPR) and ACLS and the effectiveness of their combination have not been clearly demonstrated. Methods: Using a prospective, nationwide, population-based registry of all OHCA patients in Japan, we enrolled 95,072 patients whose arrests were witnessed by bystanders and 23,127 patients witnessed by emergency medical service providers between 2005 and 2007. We divided the bystander-witnessed arrest patients into Group A (ACLS by emergency life-saving technicians without BCPR), Group B (ACLS by emergency life-saving technicians with BCPR), Group C (ACLS by physicians without BCPR) and Group D (ACLS by physicians with BCPR). The outcome data included 1-month survival and neurological outcomes determined by the cerebral performance category. Results: Among the 95,072 bystander-witnessed arrest patients, 7,722 (8.1%) were alive at 1 month, including 2,754 (2.9%) with good performance and 3,171 (3.3%) with vegetative status or worse. BCPR occurred in 42% of bystander-witnessed arrests. In comparison with Group A, the rates of good-performance survival were significantly higher in Group B (odds ratio (OR), 2.23; 95% confidence interval, 2.05 to 2.42; P < 0.01) and Group D (OR, 2.80; 95% confidence interval, 2.28 to 3.43; P < 0.01), while no significant difference was seen for Group C (OR, 1.18; 95% confidence interval, 0.86 to 1.61; P = 0.32). The occurrence of vegetative status or worse at 1 month was highest in Group C (OR, 1.92; 95% confidence interval, 1.55 to 2.37; P < 0.01). Conclusions: In this registry-based study, BCPR significantly improved the survival of OHCA with good cerebral outcome. The groups with BCPR and ACLS by physicians had the best outcomes. However, receiving ACLS by physicians without preceding BCPR significantly increased the number of patients with neurologically unfavorable outcomes.

There is a paucity of data examining nationwide population-based incidences and outcomes of pediatric out-of-hospital cardiac arrest. The objective of this study is to describe the detailed characteristics of pediatric out-of-hospital cardiac arrest by scholastic age category and to evaluate the impact of bystander cardiopulmonary resuscitation and public access-automated external defibrillators on the 1-month survival and favorable neurological status of pediatric out-of-hospital cardiac arrest patients. A nationwide, population-based, observational study. Nationwide emergency medical system in Japan. Out-of-hospital cardiac arrest patients aged ≤ 18 yr. We identified 7,624 pediatric out-of-hospital cardiac arrest patients (≤ 18 yr old) from a nationwide population-based out-of-hospital cardiac arrest database in Japan from 2005 to 2008 and stratified them into five categories by scholastic age. The overall rates of 1-month survival and favorable neurological outcomes were 11.0% and 5.1%, respectively. Bystander cardiopulmonary resuscitation resulted in a significant improvement in both 1-month survival (odds ratio 2.81; 95% confidence interval 2.30-3.44) and favorable neurological outcomes (odds ratio 4.55; 95% confidence interval 3.35-6.18). Performing public access-automated external defibrillators had a significant effect on the 1-month survival rate (odds ratio 3.51; 95% confidence interval 1.81-6.81) and favorable neurological outcomes (odds ratio 5.13; 95% confidence interval 2.64-9.96). This study demonstrated that bystander cardiopulmonary resuscitation and public access-automated external defibrillators had a significant impact on the outcomes of pediatric out-of-hospital cardiac arrest. The improved survival associated with bystander cardiopulmonary resuscitation and public access-automated external defibrillators are clinically important and are of major public health importance for school-aged out-of-hospital cardiac arrest patients.

We previously reported a new cell transplantation method in which mesenchymal stem cells (MSCs) were cultured as cell sheets. The cultured MSC sheets showed high alkaline phosphatase (ALP) activities and osteocalcin (OC) contents. In the present study, we transplanted such sheets by injection to assess whether the injectable MSC sheets could form bone tissue at subcutaneous sites. At 4 weeks after the subcutaneous injection, the injected areas showed hard mass formation. Each mass consisted of newly formed bone, as evaluated by radiographic, histological and gene expression analyses as well as three‐dimensional computed tomography (3D‐CT). Histological analyses revealed extracellular bone matrix together with osteocytes and active osteoblasts. Real‐time PCR analyses showed high ALP and OC mRNA expressions. We also injected the cell sheets into dead bone to determine whether the lost osteogenic potential could be rescued, and histological analyses revealed that the injected cell sheets supplied osteogenic potential to the dead bone. The present study clearly indicates that osteogenic MSC sheets can be transplanted via injection through a needle and that bone formation results in the injected areas. Owing to its usage of a needle for fabrication of in vivo bone tissue, this injection method can be applied as a minimally invasive approach for hard tissue reconstruction. Copyright © 2010 John Wiley & Sons, Ltd.