A composite of marrow mesenchymal stem cells and porous hydroxyapatite (HA) has in vivo osteogenic potential. To investigate factors enhancing the osteogenic potential of marrow/HA composites, we prepared a bone morphogenetic protein (BMP) fraction from the 4M guanidine extract of bovine bone by heparin-sepharose affinity chromatography. Marrow/HA composites or composites containing marrow mesenchymal stem cells, BMP, and HA (marrow/BMP/HA composites) were implanted subcutaneously in 7-week-old male Fischer rats. BMP/HA composites and HA alone were also implanted. The implants were harvested after 2, 4, or 8 weeks and were prepared for histological and biochemical studies. Histological examination showed obvious de novo bone formation together with active osteoblasts at 2 weeks, as well as more extensive bone formation at 4 and 8 weeks in many pores of the marrow/ BMP/HA composites. The marrow/HA composites did not induce bone formation at 2 weeks, but there was moderate bone formation at 4 weeks. At 2 weeks, only marrow/BMP/ HA composites resulted in intensive osteogenic activity, judging from alkaline phosphatase and osteocalcin expression at both the protein and gene levels. These results indicate that the combination of marrow mesenchymal stem cells, porous HA, and BMP synergistically enhances osteogenic potential, and may provide a rational basis for their clinical application, although further in vivo experiment is needed.

After 2-vein occlusion, continuous intraventricular administration of BDNF protected the cerebral cortex against apoptosis and reduced infarct size without affecting rCBF.

This article describes the prefabrication of a vascularized bone graft composed of autologous particulate cancellous bone and marrow (PCBM), a vessel bundle, and a biodegradable membrane. The PCBM was placed around the saphenous vessel bundle of rats and rolled with a biodegradable membrane of L-lactide-epsilon-caprolactone copolymer to prepare the prefabricated vascularized bone graft (group A). As controls, combinations of PCBM and membrane (group B), vessel bundle and membrane (group C), and PCBM and vessel bundle (group D) were prepared. A radiographic study revealed radio-opacity in the implantation site of group A 1 week later, in contrast to the other groups. Newly formed bone in the membrane roll was histologically confirmed, and neomicrovasculature circulating from the vessel bundle through the newly formed bone tissue was observed. The increase in alkaline phosphatase activity and osteocalcin content was significant for the group A preparation compared with the other groups. We concluded that the combination of autologous PCBM, a vessel bundle, and a biodegradable membrane was promising in the prefabrication of vascularized bone with good blood circulation.

OBJECTIVEThe neurocognitive course of patients who have undergone cerebral revascularization has been the subject of many studies, and the reported effects of carotid artery stenting (CAS) on cognitive function have varied from study to study. The authors hypothesized that cognitive amelioration after CAS is associated with alteration of the default mode network (DMN) connectivity, and they investigated the correlation between functional connectivity (FC) of the DMN and post-CAS changes in cognitive function in order to find a clinical marker that can be used to predict the effect of cerebral revascularization on patients’ cognitive function in this preliminary exploratory study.METHODSThe authors examined post-CAS changes in cognitive function in relation to FC in patients treated for unilateral carotid artery stenosis. Resting-state functional MRI (rs-fMRI) was performed with a 3-T scanner before and 6 months after CAS in 8 patients. Neuropsychological tests (Wechsler Adult Intelligence Scale III and Wechsler Memory Scale–Revised) were administered to each patient before and 6 months after CAS. The DMN was mapped for each patient through independent component analysis of the rs-fMR images, and the correlation between FC of the DMN and post-CAS change in cognitive function was analyzed on a voxel level. Multivariable regression analysis was performed to identify preoperative factors associated with a post-CAS change in cognitive function.RESULTSPost-CAS cognitive function varied between patients and between categories of neuropsychological tests. Although there was no significant overall improvement in Working Memory scores after CAS, post-CAS Working Memory scores changed in negative correlation with changes in FC between the DMN and the precentral/superior frontal gyrus and between the DMN and the middle frontal gyrus. In addition, the preoperative FC between those areas correlated positively with the post-CAS improvement in working memory.CONCLUSIONSFC between the DMN and working memory–related areas is closely associated with improvement in working memory after CAS. Preoperative analysis of FC of the DMN may be useful for predicting postoperative improvement in the working memory of patients being treated for unilateral stenosis of the extracranial internal carotid artery.Clinical trial registration no.: UMIN000020045 (www.umin.ac.jp/ctr/index.htm)