Growth factors in serum-free conditioned media from human bone marrow-derived mesenchymal stem cells (MSC-CM) are known to be effective in bone regeneration. However, the secretomes in MSC-CM that act as active ingredients for bone regeneration, as well as their mechanisms, remains unclear. Exosomes, components of MSC-CM, provide the recipient cells with genetic information and enhance the recipient cellular paracrine stimulation, which contributes to tissue regeneration. We hypothesized that MSC-CM-derived exosomes (MSC-Exo) promoted bone regeneration, and that angiogenesis was a key step. Here, we prepared an MSC-Exo group, MSC-CM group, and Exo-antiVEGF group (MSC-Exo with angiogenesis inhibitor), and examined the osteogenic and angiogenic potential in MSCs. Furthermore, we used a rat model of calvaria bone defect and implanted each sample to evaluate bone formation weekly, until week 4 after treatment. Results showed that MSC-Exo enhanced cellular migration and osteogenic and angiogenic gene expression in MSCs compared to that in other groups. In vivo, early bone formation by MSC-Exo was also confirmed. Two weeks after implantation, the newly formed bone area was 31.5 ± 6.5% in the MSC-Exo group while those in the control and Exo-antiVEGF groups were 15.4 ± 4.4% and 8.7 ± 1.1%, respectively. Four weeks after implantation, differences in the area between the MSC-Exo group and the Exo-antiVEGF or control groups were further broadened. Histologically, notable accumulation of osteoblast-like cells and vascular endothelial cells was observed in the MSC-Exo group; however, fewer cells were found in the Exo-antiVEGF and control groups.In conclusion, MSC-Exo promoted bone regeneration during early stages, as well as enhanced angiogenesis. Considering the tissue regeneration with transplanted cells and their secretomes, this study suggests that exosomes might play an important role, especially in angiogenesis.

Amyotrophic lateral sclerosis (ALS) may be accompanied by frontotemporal dementia (FTD). We report a case of glial mixed tau and TDP-43 proteinopathies in a Japanese patient diagnosed clinically as having ALS-D. Autopsy revealed loss of lower motor neurons and degeneration of the pyramidal tracts in the spinal cord and brain stem. The brain showed frontotemporal lobar degeneration (FTLD), the most severe neuronal loss and gliosis being evident in the precentral gyrus. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. AT8 immunostaining revealed that predominant occurrence of astrocytic tau lesions termed globular astrocytic inclusions (GAIs) was a feature of the affected regions. These GAIs were Gallyas-Braak negative. Neuronal and oligodendrocytic tau lesions were comparatively scarce. pS409/410 immunostaining also revealed similar neuronal and glial TDP-43 lesions. Interestingly, occasional co-localization of tau and TDP-43 was evident in the GAIs. Immunoblot analyses revealed band patterns characteristic of a 4-repeat (4R) tauopathy, corticobasal degeneration and a TDP-43 proteinopathy, ALS/FTLD-TDP Type B. No mutations were found in the MAPT or TDP-43 genes. We consider that this patient harbored a distinct, sporadic globular glial mixed 4R tau and TDP-43 proteinopathy associated with motor neuron disease and FTD.

Objective: Postoperative knee range of motion (ROM) is among the most important factors influencing patient satisfaction after total knee arthroplasty (TKA). The purpose of this study was to clarify the time course of improvement in knee ROM up to 12 months after TKA, including intraoperative knee ROM after implantation, and to clarify a target ROM for rehabilitation after TKA.Patients and Methods: In total, 39 knee joints in 26 patients with osteoarthritis who underwent TKA (retaining the posterior cruciate ligament) were evaluated. Goniometry was used to measure the knee range of extension and flexion preoperatively; intraoperatively; at 1 and 2 weeks after TKA; and then at 1, 3, 6, and 12 months after TKA.Results: The postoperative extension range gradually improved up to a maximum at 6 months after TKA; there were no significant differences in the extension range between intraoperative and 6 months after TKA, intraoperative and 12 months after TKA, or 6 and 12 months after TKA. The postoperative flexion range gradually improved, with the maximum improvement observed at 3 months after TKA; there were no significant differences in the flexion range before TKA and 3, 6, and 12 months after TKA. There were no significant differences between flexion ROM measured at 3, 6, and 12 months after TKA.Conclusions: The changes in the knee range of extension plateaued 6 months after TKA, and those in the knee range of flexion plateaued 3 months after TKA. The target range of extension for rehabilitation from 6 months to 12 months after TKA was the intraoperative range, and the target range of flexion for rehabilitation from 3 months to 12 months after TKA was the preoperative range.

BackgroundThe Hybrid Assistive Limb (HAL®) is an exoskeleton wearable robot suit that assists in voluntary control of knee and hip joint motion. There have been several studies on HAL intervention effects in stroke, spinal cord injury, and cerebral palsy. However, no study has investigated HAL intervention for patients with cerebral palsy after surgery.Case presentationWe report a case of using HAL in a postoperative patient with cerebral palsy. A 15-year-old boy was diagnosed with spastic diplegia cerebral palsy Gross Motor Function Classification System level IV, with knee flection contracture, equinus foot, and paralysis of the right upper extremity with adduction contracture. He underwent tendon lengthening of the bilateral hamstrings and Achilles tendons. Although the flexion contractures of the bilateral knees and equinus foot improved, muscle strength decreased after the soft tissue surgery. HAL intervention was performed twice during postoperative months 10 and 11. Walking speed, stride, and cadence were increased after HAL intervention. Post HAL intervention, extension angles of the knee in stance phase and hip in the pre-swing phase were improved. In the gait cycle, the proportion of terminal stance in the stance and swing phase was increased.ConclusionsHybrid Assistive Limb intervention for postoperative patients with cerebral palsy whose muscle strength decreases can enhance improvement in walking ability. Further studies are needed to examine the safety and potential application of HAL in this setting.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-3311-z) contains supplementary material, which is available to authorized users.

Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are types of major TDP-43 (43-kDa TAR DNA-binding protein) proteinopathy. Cortical TDP-43 pathology has been analyzed in detail in cases of FTLD-TDP, but is still unclear in cases of ALS. We attempted to clarify the cortical and subcortical TDP-43 pathology in Japanese cases of sporadic ALS (n = 96) using an antibody specific to phosphorylated TDP-43 (pTDP-43). The cases were divided into two groups: those without pTDP-43-positive neuronal cytoplasmic inclusions in the hippocampal dentate granule cells (Type 1, n = 63), and those with such inclusions (Type 2, n = 33). Furthermore, the Type 2 cases were divided into two subgroups based on semi-quantitative estimation of pTDP-43-positive dystrophic neurites (DNs) in the temporal neocortex: Type 2a (accompanied by no or few DNs, n = 22) and Type 2b (accompanied by abundant DNs, n = 11). Clinico-pathologic analysis revealed that cognitive impairment was a feature in patients with Type 2a and Type 2b, but not in those with Type 1, and that importantly, Type 2b is a distinct subtype characterized by a poor prognosis despite the less severe loss of lower motor neurons, the unusual subcortical dendrospinal pTDP-43 pathology, and more prominent glial involvement in cortical pTDP-43 pathology than other two groups. Considering the patient survival time and severity of motor neuron loss in each group, transition from Type 1 to Type 2, or from Type 2a to Type 2b during the disease course appeared unlikely. Therefore, each of these three groups was regarded as an independent subtype.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0335-2) contains supplementary material, which is available to authorized users.