Language：English   Publishing type：Research paper (scientific journal)  

The primary objective of this study was to investigate the potential facilitating effects of daily rehabilitation for chronic cerebral ischemia following the intravenous infusion of mesenchymal stem cells (MSC) in rats. The middle cerebral artery (MCA) was occluded by intraluminal occlusion using a microfilament (MCAO). Eight weeks after MCAO induction, the rats were used as a chronic cerebral ischemia model. Four experimental groups were studied: Vehicle group (medium only, no cells); Rehab group (vehicle + rehabilitation), MSC group (MSC only); and Combined group (MSC + rehabilitation). Rat MSCs were intravenously infused eight weeks after MCAO induction, and the rats received daily rehabilitation through treadmill exercise for 20 min. Behavioral testing, lesion volume assessment using magnetic resonance imaging (MRI), and histological analysis were performed during the observation period until 16 weeks after MCAO induction. All treated animals showed functional improvement compared with the Vehicle group; however, the therapeutic efficacy was greatest in the Combined group. The combination therapy is associated with enhanced neural plasticity shown with histological analysis and MRI diffusion tensor imaging. These findings provide behavioral evidence for enhanced recovery by combined therapy with rehabilitation and intravenous infusion of MSCs, and may form the basis for the development of clinical protocols in the future.

DOI： 10.1016/j.brainres.2023.148709

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本核医学会  

Ichushi

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Malignant glioma is a highly invasive tumor, and elucidating the glioma invasion mechanism is essential for developing novel therapies. We aimed to highlight actin alpha 2, smooth muscle (ACTA2) as potential biomarkers of brain invasion and distant recurrence in malignant gliomas. Using the human malignant glioma cell line, U251MG, we generated ACTA2 knockdown (KD) cells treated with small interfering RNA, and the cell motility and proliferation of the ACTA2 KD group were analyzed. Furthermore, tumor samples from 12 glioma patients who underwent reoperation at the time of tumor recurrence were utilized to measure ACTA2 expression in the tumors before and after recurrence. Thereafter, we examined how ACTA2 expression correlates with the time to tumor recurrence and the mode of recurrence. The results showed that the ACTA2 KD group demonstrated a decline in the mean motion distance and proliferative capacity compared to the control group. In the clinical glioma samples, ACTA2 expression was remarkably increased in recurrent samples compared to the primary samples from the same patients, and the higher the change in ACTCA2 expression from the start to relapse, the shorter the progression-free survival. In conclusion, ACTA2 may be involved in distant recurrence in clinical gliomas.

DOI： 10.3390/brainsci13101477

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Spinal cord injury (SCI) can cause paralysis with a high disease burden with limited treatment options. A single intravenous infusion of mesenchymal stem cells (MSCs) improves motor function in rat SCI models, possibly through the induction of axonal sprouting and remyelination. Repeated infusions (thrice at weekly intervals) of MSCs were administered to rats with chronic SCI to determine if multiple-dosing regimens enhance motor improvement. Chronic SCI rats were randomized and infused with vehicle (vehicle), single MSC injection at week 6 (MSC-1) or repeatedly injections of MSCs at 6, 7, and 8 weeks (MSC-3) after SCI induction. In addition, a single high dose of MSCs (HD-MSC) equivalent to thrice the single dose was infused at week 6. Locomotor function, light and electron microscopy, immunohistochemistry and ex vivo diffusion tensor imaging were performed. Repeated infusion of MSCs (MSC-3) provided the greatest functional recovery compared to single and single high-dose infusions. The density of remyelinated axons in the injured spinal cord was the greatest in the MSC-3 group, followed by the MSC-1, HD-MSC and vehicle groups. Increased sprouting of the corticospinal tract and serotonergic axon density was the greatest in the MSC-3 group, followed by MSC-1, HD-MSC, and vehicle groups. Repeated infusion of MSCs over three weeks resulted in greater functional improvement than single administration of MSCs, even when the number of infused cells was tripled. MSC-treated rats showed axonal sprouting and remyelination in the chronic phase of SCI.

DOI： 10.1016/j.brainres.2023.148484

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Spine Surgery and Related Research  

DOI： 10.22603/ssrr.2022-0234

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Perinatal brain injury is multifactorial and primarily associated with brain prematurity, inflammation, and hypoxia-ischemia. Although recent advances in perinatal medicine have improved the survival rates of preterm infants, neurodevelopmental disorders remain a significant complication. We tested whether the intravenous infusion of mesenchymal stem cells (MSCs) had therapeutic efficacy against perinatal brain injury in rats. METHODS: Pregnant rats at embryonic day (E) 18 received lipopolysaccharide and the pups were born at E21. On postnatal day (PND) 7, the left common carotid artery of each pup was ligated, and they were exposed to 8% oxygen for 2 h. They were randomized on PND10, and MSCs or vehicle were intravenously infused. We performed behavioral assessments, measured brain volume using MRI, and performed histological analyses on PND49. RESULTS: Infused MSCs showed functional improvements in our model. In vivo MRI revealed that MSC infusion increased non-ischemic brain volume compared to the vehicle group. Histological analyses showed that cortical thickness, the number of NeuN+ and GAD67+ cells, and synaptophysin density in the non-ischemic hemisphere in the MSC group were greater than the vehicle group, but less than the control group. CONCLUSIONS: Infused MSCs improve sensorimotor and cognitive functions in perinatal brain injury and enhance neuronal growth. IMPACT: Intravenous infusion of MSCs improved neurological function in rats with perinatal brain injury, including motor, sensorimotor, cognitive, spatial, and learning memory. Infused MSCs increased residual (non-ischemic) tissue volume, number of neuronal cells, GABAergic cells, and cortical synapses in the contralesional (right) hemisphere. Intravenous administration of MSC might be suitable for the treatment of perinatal brain injury.

DOI： 10.1038/s41390-023-02717-9

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Magnetic resonance angiography (MRA) is an important tool in rat models of cerebrovascular disease. Although MRA has long been used in rodents, the image quality is typically not as high as that observed in clinical practice. Moreover, studies on MRA image quality in rats are limited. This study aimed to develop a practical high-spatial-resolution MRA protocol for imaging cerebral arteries in rats. NEW METHOD: We used the "half position method" regarding coil placement and modified the imaging parameters and image reconstruction method. We applied this new imaging method to measure maturation-related signal changes on rat MRAs. RESULTS: The new practical high-spatial-resolution MRA imaging protocol obtained a signal intensity up to 3.5 times that obtained using a basic coil system, simply by modifying the coil placement method. This method allowed the detection of a gradual decrease in the signal in cerebral vessels with maturation. COMPARISON WITH EXISTING METHODS: A high-spatial-resolution MRA for rats was obtained with an imaging time of approximately 100 min. Comparable resolution and image quality were obtained using the new protocol with an imaging time of 30 min CONCLUSIONS: The new practical high-spatial-resolution MRA protocol can be implemented simply and successfully to achieve high image quality with an imaging time of approximately 30 min. This protocol will benefit researchers performing MRA imaging in cerebral artery studies in rats.

DOI： 10.1016/j.jneumeth.2023.109784

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Intravenous infusion of stem cells is a minimally invasive cellular delivery method, though a few have been reported in a critical limb-threatening ischemia (CLTI) animal model or patients. In the present study, we hypothesized that intravenous infusion of bone-marrow derived mesenchymal stem cells (MSCs) improves tissue perfusion in a rat hindlimb ischemia model. Hindlimb ischemia was generated in Sprague-Dawley rats by femoral artery removal, then seven days after ischemic induction intravenous infusion of 1 × 106 MSCs (cell group) or vehicle (control group) was performed. As compared with the control, tissue perfusion was significantly increased in the cell group. Histological findings showed that capillary density was significantly increased in the cell group, with infused green fluorescent protein (GFP)-MSCs distributed in the ischemic limb. Furthermore, gene expression of vascular endothelial growth factor (VEGF) was significantly increased in ischemic hindlimb muscle tissues of rats treated with MSC infusion. In conclusion, intravenous infusion of bone-marrow derived MSCs improved tissue perfusion in ischemic hindlimbs through angiogenesis, suggesting that intravenous infusion of MSCs was a promising cell delivery method for treatment of CLTI.

DOI： 10.1038/s41598-022-18485-1

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Mary Ann Liebert Inc  

Although limited spontaneous recovery occurs after spinal cord injury (SCI), current knowledge reveals that multiple forms of axon growth in spared axons can lead to circuit reorganization and a detour or relay pathways. This hypothesis has been derived mainly from studies of the corticospinal tract (CST), which is the primary descending motor pathway in mammals. The major CST is the dorsal CST (dCST), being the major projection from cortex to spinal cord. Two other components often called "minor" pathways are the ventral and the dorsal lateral CSTs, which may play an important role in spontaneous recovery. Intravenous infusion of mesenchymal stem cells (MSCs) provides functional improvement after SCI with an enhancement of axonal sprouting of CSTs. Detailed morphological changes of CST pathways, however, have not been fully elucidated. The primary objective was to evaluate detailed changes in descending CST projections in SCI after MSC infusion. The MSCs were infused intravenously one day after SCI. A combination of adeno-associated viral vector (AAV), which is an anterograde and non-transsynaptic axonal tracer, was injected 14 days after SCI induction. The AAV with advanced tissue clearing techniques were used to visualize the distribution pattern and high-resolution features of the individual axons coursing from above to below the lesion. The results demonstrated increased observable axonal connections between the dCST and axons in the lateral funiculus, both rostral and caudal to the lesion core, and an increase in observable axons in the dCST below the lesion. This increased axonal network could contribute to functional recovery by providing greater input to the spinal cord below the lesion.

Other Link： https://www.liebertpub.com/doi/pdf/10.1089/neu.2022.0106

DOI： 10.1089/neu.2022.0106

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JMIR Publications Inc.  

Background

Brain injuries resulting from motor vehicle accidents and falls, as well as hypoxic insults and other conditions, are one of the leading causes of disability and death in the world. Current treatments are limited but include continuous rehabilitation, especially for chronic brain injury. Recent studies have demonstrated that the intravenous infusion of mesenchymal stem cells (MSCs) has therapeutic efficacy for several neurological diseases, including stroke and spinal cord injury.

Objective

The objective of our investigator-initiated clinical trial is to assess the safety and potential efficacy of the intravenous infusion of autoserum-expanded autologous MSCs for patients with chronic brain injury.

Methods

The (phase 2) trial will be a single-arm, open-label trial with the primary objective of confirming the safety and efficacy of autoserum-expanded autologous MSCs (STR-01; produced under good manufacturing practices) when administered to patients with chronic brain injury. The estimated number of enrolled participants is 6 to 20 patients with a modified Rankin Scale grade of 3 to 5. The assessment of safety and the proportion of cases in which the modified Rankin Scale grade improves by 1 point or more at 180 days after the injection of STR-01 will be performed after MSC infusion.

Results

We received approval for our clinical trial from the Japanese Pharmaceuticals and Medical Devices Agency on December 12, 2017. The trial will be completed on June 11, 2023. The registration term is 5 years. The recruitment of the patients for this trial started on April 20, 2018, at Sapporo Medical University Hospital in Japan.

Conclusions

Our phase 2 study will aim to address the safety and efficacy of the intravenous infusion of MSCs for patients with chronic brain injury. The use of STR-01 has been performed for patients with cerebral infarction and spinal cord injury, providing encouraging results. The potential therapeutic efficacy of the systemic administration of autoserum-expanded autologous MSCs for chronic brain injury should be evaluated, given its safety and promising results for stroke and spinal cord injury.

Trial Registration

Japan Medical Association Center for Clinical Trials JMA-IIA00333; https://tinyurl.com/nzkdfnbc

International Registered Report Identifier (IRRID)

DERR1-10.2196/37898

DOI： 10.2196/37898

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Background Selecting the appropriate direct oral anticoagulants (DOACs) for embolic ischemic stroke patients, especially on concurrent antiplatelet therapy, is important. However, a limited number of studies have reported on the pharmacological differences in platelet aggregation of each DOAC. We aimed to evaluate the antiplatelet effects of selected DOACs, by comparing dabigatran (a direct oral thrombin inhibitor) and factor Xa (FXa) inhibitors (apixaban and rivaroxaban) in patients who had suffered a cardioembolic stroke. Methods We retrospectively evaluated 12 patients diagnosed with a cardioembolic stroke who took any DOAC without an antiplatelet drug and underwent platelet aggregation tests within 60 days from the onset of symptoms. The platelet aggregation tests were analyzed by both light transmission aggregometry and VerifyNow®. Results Six patients (50%) took dabigatran, while the other six (50%) took an FXa inhibitor (n = 4 for apixaban and n = 2 for rivaroxaban). From the light transmission aggregometry analysis, it was found that the maximal extent of aggregation for adenosine diphosphate (ADP) was significantly higher with dabigatran than with FXa inhibitors, and the ED50 value of ADP on platelet aggregation was significantly lower with dabigatran than with FXa inhibitors. Moreover, the VerifyNow® analyses revealed that P2Y12 reaction units were significantly higher with dabigatran than with FXa inhibitors. Conclusions Dabigatran had little impact on platelet aggregation compared to FXa inhibitors in patients who had suffered a cardioembolic stroke with atrial fibrillation, and who took DOACs for secondary prevention within 60 days from the onset.

DOI： 10.1016/j.jstrokecerebrovasdis.2022.106520

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The purple-flesh potato (Solanum tuberosum L.) cultivar "Shadow Queen" (SQ) naturally contains anthocyanins. This randomized, double-blind, placebo-controlled study determines whether ingesting purple potatoes increases the number of mesenchymal stem cells (MSC) and improves stress response, a minor health complaint in healthy adults (registration number: UMIN000038876). A total of 15 healthy subjects (ages: 50-70 years) with minor health complaints were randomly assigned to one of two groups. For 8 weeks, the placebo group received placebo potatoes cv. "Haruka" and the test group received test potato cv. SQ containing 45 mg anthocyanin. The MSC count and several stress responses were analyzed at weeks 0 and 8 of the intake periods. The ingestion of a SQ potato did not affect the MSC count but markedly improved psychological stress response, irritability, and depression as minor health complaints compared with "Haruka". No adverse effects were noted. Hence, an 8-week intake of SQ could improve stress responses.

DOI： 10.3390/nu14122446

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Stroke is a major cause of long-term disability, and there are few effective treatments that improve function in patients during the chronic phase of stroke. Previous research has shown that single systemic infusion of mesenchymal stem cells (MSCs) improves motor function in acute and chronic cerebral ischemia models in rats. A possible mechanism that could explain such an event includes the enhanced neural connections between cerebral hemispheres that contribute to therapeutic effects. In the present study, repeated infusions (3 times at weekly intervals) of MSCs were administered in a rat model of chronic stroke to determine if multiple dosing facilitated plasticity in neural connections. METHODS: The authors induced middle cerebral artery occlusion (MCAO) in rats and, 8 weeks thereafter, used them as a chronic stroke model. The rats with MCAO were randomized and intravenously infused with vehicle only (vehicle group); with MSCs at week 8 (single administration: MSC-1 group); or with MSCs at weeks 8, 9, and 10 (3 times, repeated administration: MSC-3 group) via femoral veins. Ischemic lesion volume and behavioral performance were examined. Fifteen weeks after induction of MCAO, the thickness of the corpus callosum (CC) was determined using Nissl staining. Immunohistochemical analysis of the CC was performed using anti-neurofilament antibody. Interhemispheric connections through the CC were assessed ex vivo by diffusion tensor imaging. RESULTS: Motor recovery was better in the MSC-3 group than in the MSC-1 group. In each group, there was no change in the ischemic volume before and after infusion. However, both thickness and optical density of neurofilament staining in the CC were greater in the MSC-3 group, followed by the MSC-1 group, and then the vehicle group. The increased thickness and optical density of neurofilament in the CC correlated with motor function at 15 weeks following induction of MCAO. Preserved neural tracts that ran through interhemispheric connections via the CC were also more extensive in the MSC-3 group, followed by the MSC-1 group and then the vehicle group, as observed ex vivo using diffusion tensor imaging. CONCLUSIONS: These results indicate that repeated systemic administration of MSCs over 3 weeks resulted in greater functional improvement as compared to single administration and/or vehicle infusion. In addition, administration of MSCs is associated with promotion of interhemispheric connectivity through the CC in the chronic phase of cerebral infarction.

DOI： 10.3171/2021.8.JNS21687

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Background

Interstitial cystitis/bladder pain syndrome (IC/BPS) categorized with and without Hunner lesions is a condition that displays chronic pelvic pain related to the bladder with no efficacious treatment options. There are strong associations suggested between Hunner-type IC and autoimmune diseases. Recently, we established an animal model of Hunner-type IC using a Toll-like receptor-7 (TLR7) agonist. Intravenous infusion of mesenchymal stem cells (MSCs) can be used to treat injury via multimodal and orchestrated therapeutic mechanisms including anti-inflammatory effects. Here, we investigated whether infused MSCs elicit therapeutic efficacy associated with the TLR7-related anti-inflammatory pathway in our Hunner-type IC model.

Methods

Voiding behaviors were monitored 24 h prior to the Loxoribine (LX), which is a TLR7 agonist instillation in order to establish a Hunner-type IC model (from − 24 to 0 h) in female Sprague–Dawley rats. LX was instilled transurethrally into the bladder. At 0 h, the initial freezing behavior test confirmed that no freezing behavior was observed in any of the animals. The LX-instilled animals were randomized. Randomized LX-instilled rats were intravenously infused with MSCs or with vehicle through the right external jugular vein. Sampling tissue for green fluorescent protein (GFP)-positive MSCs were carried out at 48 h. Second voiding behavior tests were monitored from 72 to 96 h. After the final evaluation of the freezing behavior test at 96 h after LX instillation (72 h after MSC or vehicle infusion), histological evaluation with H&E staining and quantitative real-time polymerase chain reaction (RT-PCR) to analyze the mRNA expression levels of inflammatory cytokines were performed.

Results

Freezing behavior was reduced in the MSC group, and voiding behavior in the MSC group did not deteriorate. Hematoxylin–eosin staining showed that mucosal edema, leukocyte infiltration, and hemorrhage were suppressed in the MSC group. The relative expression of interferon-β mRNA in the bladder of the MSC group was inhibited. Numerous GFP-positive MSCs were distributed mainly in the submucosal and mucosal layers of the inflammatory bladder wall.

Conclusion

Intravenous infusion of MSCs may have therapeutic efficacy in a LX-instilled Hunner-type IC rat model via a TLR7-related anti-inflammatory pathway.

Other Link： https://link.springer.com/article/10.1186/s12894-021-00923-3/fulltext.html

DOI： 10.1186/s12894-021-00923-3

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative fatal disorder in which motor neurons within the brain and spinal cord degenerate. A single infusion of mesenchymal stem cells (MSCs) delays disease progression by protecting motor neurons and restoring the blood-spinal cord barrier in the SOD1G93A transgenic ALS rat model. However, the therapeutic effect of a single infusion of MSCs is transient and does not block disease progression. In this study, we demonstrated that repeated administration of MSCs (weekly, four times) increased the survival period, protected motor functions, and reduced deterioration of locomotor activity compared to a single infusion and vehicle infusion, after which rats displayed progressive deterioration of hind limb function. We also compared the days until gait ability was lost in rats and found that the repeated-infused group maintained gait ability compared to the single-infusion and vehicle-infusion groups. These results suggest that repeated administration of MSCs may prevent the deterioration of motor function and extend the lifespan in ALS.

DOI： 10.1186/s13041-021-00787-6

PubMed

researchmap

Language：Japanese   Publisher：(公社)日本放射線技術学会  

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J01192&link_issn=&doc_id=20211101390012&doc_link_id=10.6009%2Fjjrt.2021_JSRT_77.10.1238&url=https%3A%2F%2Fdoi.org%2F10.6009%2Fjjrt.2021_JSRT_77.10.1238&type=Crossref&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00002_2.gif

Ichushi

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1097/prs.0000000000008327

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press ({OUP})  

OBJECTIVES: Ischaemic spinal cord injury (SCI) is one of the most serious complications of aortic surgery. Ischaemic SCIs occur due to various aetiologies, and prediction of the risk is difficult. Magnetic resonance imaging (MRI) is useful to detect the details of spinal cord infarction. There are few studies about MRI for evaluating ischaemic SCI after cardiovascular surgery and aortic events. We report 9 cases of postoperative ischaemic SCI and analyse their MRI features. METHODS: T2-weighted MRI scans of 9 patients who developed ischaemic SCI due to cardiovascular surgery and aortic events between 2012 and 2017 were evaluated. RESULTS: In all patients, high-intensity areas were observed on T2-weighted magnetic resonance images. The site of infarction was the thoracic spinal cord level (9 cases) and additionally at the lumbar spinal cord level (5 cases). The area of infarction area was categorized based on the arterial territory: anterior spinal artery territory (3 cases), posterior spinal artery territory (2 cases), spinal sulcal artery territory (1 case) and artery of Adamkiewicz territory (3 cases). CONCLUSIONS: MRI revealed the infarction sites in all cases and the differences in the infarction patterns in each case. MRI could thus be useful for investigating the aetiology of ischaemic SCI following aortic surgeries and events.

DOI： 10.1093/ejcts/ezaa476

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

OBJECTIVE: Reperfusion therapy is a standard therapeutic strategy for acute stroke. Non-favorable outcomes are thought to partially result from impaired microcirculatory flow in ischemic tissue. Intravenous infusion of mesenchymal stem cells (MSCs) reduces stroke volume and improves behavioral function in stroke. One suggested therapeutic mechanism is the restoration of the microvasculature. The goal of this study was to determine whether infused MSCs enhance the therapeutic efficacy of reperfusion therapy following stroke in rats. METHODS: First, to establish a transient middle cerebral artery occlusion (MCAO) model displaying approximately identical neurologic function and lesion volume as seen in permanent MCAO (pMCAO) at day 7 after stroke induction, we transiently occluded the MCA for 90, 110, and 120 minutes. We found that the 110-minute occlusion met these criteria and was used as the transient MCAO (tMCAO) model. Next, 4 MCAO groups were used to compare the therapeutic efficacy of infused MSCs: (1) pMCAO+vehicle, (2) tMCAO+vehicle, (3) pMCAO+MSC, and (4) tMCAO+MSC. Our ischemic model was a unique ischemic model system in which both pMCAO and tMCAO provided similar outcomes during the study period in the groups without MSC infusion groups. Behavioral performance, ischemic volume, and regional cerebral blood flow (rCBF) using arterial spin labeling-magnetic resonance imaging and histologic evaluation of microvasculature was performed. RESULTS: The behavioral function, rCBF, and restoration of microvasculature were greater in group 4 than in group 3. Thus, infused MSCs facilitated the therapeutic efficacy of MCA reperfusion in this rat model system. CONCLUSIONS: Intravenous infusion of MSCs may enhance therapeutic efficacy of reperfusion therapy.

DOI： 10.1016/j.wneu.2021.02.056

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

ALS is a devastating neurodegenerative disease with few curative strategies. Both sporadic and familial ALS display common clinical features that show progressive paralysis. The pathogenesis remains unclear, but disruption of the blood-spinal cord barrier (BSCB) may contribute to the degeneration of motor neurons. Thus, restoration of the disrupted BSCB and neuroprotection for degenerating motor neurons could be therapeutic targets. We tested the hypothesis that an intravenous infusion of MSCs would delay disease progression through the preservation of BSCB function and increased expression of a neurotrophic factor, neurturin, in SOD1G93A ALS rats. When the open-field locomotor function was under 16 on the Basso, Beattie, and Bresnahan (BBB) scoring scale, the rats were randomized into two groups; one received an intravenous infusion of MSCs, while the other received vehicle alone. Locomotor function was recorded using BBB scoring and rotarod testing. Histological analyses, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), were performed. The MSC group exhibited reduced deterioration of locomotor activity compared to the vehicle group, which displayed progressive deterioration of hind limb function. We observed the protection of motor neuron loss and preservation of microvasculature using Evans blue leakage and immunohistochemical analyses in the MSC group. Confocal microscopy revealed infused green fluorescent protein+ (GFP+) MSCs in the spinal cord, and the GFP gene was detected by nested PCR. Neurturin expression levels were significantly higher in the MSC group. Thus, restoration of the BSCB and the protection of motor neurons might be contributing mechanisms to delay disease progression in SOD1G93A ALS rats.

DOI： 10.1016/j.brainres.2021.147296

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media {LLC}  

DOI： 10.1038/s41684-021-00722-1

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Although spinal cord injury (SCI) is a major cause of disability, current therapeutic options remain limited. Recent progress in cellular therapy with mesenchymal stem cells (MSCs) has provided improved function in animal models of SCI. We investigated the safety and feasibility of intravenous infusion of MSCs for SCI patients and assessed functional status after MSC infusion. METHODS: In this phase 2 study of intravenous infusion of autologous MSCs cultured in auto-serum, a single infusion of MSCs under Good Manufacturing Practice (GMP) production was delivered in 13 SCI patients. In addition to assessing feasibility and safety, neurological function was assessed using the American Spinal Injury Association Impairment Scale (ASIA), International Standards for Neurological and Functional Classification of Spinal Cord (ISCSCI-92). Ability of daily living was assessed using Spinal Cord Independence Measure (SCIM-III). The study protocol was based on advice provided by the Pharmaceuticals and Medical Devices Agency in Japan. The trial was registered with the Japan Medical Association (JMA-IIA00154). RESULTS: No serious adverse events were associated with MSC injection. There was neurologic improvement based on ASIA grade in 12 of the 13 patients at six months post-MSC infusion. Five of six patients classified as ASIA A prior to MSC infusion improved to ASIA B (3/6) or ASIA C (2/6), two ASIA B patients improved to ASIA C (1/2) or ASIA D (1/2), five ASIA C patients improved and reached a functional status of ASIA D (5/5). Notably, improvement from ASIA C to ASIA D was observed one day following MSC infusion for all five patients. Assessment of both ISCSCI-92, SCIM-III also demonstrated functional improvements at six months after MSC infusion, compared to the scores prior to MSC infusion in all patients. CONCLUSION: While we emphasize that this study was unblinded, and does not exclude placebo effects or a contribution of endogenous recovery or observer bias, our observations provide evidence supporting the feasibility, safety and functional improvements of infused MSCs into patients with SCI.

DOI： 10.1016/j.clineuro.2021.106565

PubMed

researchmap

Language：Japanese   Publisher：Japanese Society of Radiological Technology  

Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I031795876

DOI： 10.6009/jjrt.2021_JSRT_77.10.1238

CiNii Research

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Intravenous infusion of mesenchymal stem cells (MSCs) has been reported to provide therapeutic efficacy via microvascular remodeling in a spontaneously hypertensive rat. In this study, we demonstrate that intravenous infusion of MSCs increased the survival rate in a spontaneously hypertensive (stroke prone) rat model in which organs including kidney, brain, heart and liver are damaged during aging due to spontaneous hypertension. Gene expression analysis indicated that infused MSCs activates transforming growth factor-β1-smad3/forkhead box O1 signaling pathway. Renal dysfunction was recovered after MSC infusion. Collectively, intravenous infusion of MSC may extend lifespan in this model system.

DOI： 10.1016/j.heliyon.2020.e05833

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

Ischemic spinal cord injury (iSCI) is a devastating complication of aortic surgery, with few strategies for prevention. Intravenous infusion of mesenchymal stem cells (MSCs) for iSCI has been shown to provide functional improvement through protection of gray matter. The purpose of this study was to investigate additional mechanisms which may exert therapeutic efficacy in iSCI. Severe iSCI was created to occlude the descending aorta, which was cross-clamped 5 mm distal to the left subclavian artery for 16 min. One day after iSCI induction, iSCI rats were randomized into two groups: one received intravenous infusion of MSCs (MSC-group), the other received vehicle (no cells; vehicle-group). Locomotor function and in vivo MRI were recorded. H&E, Nissl and toluidine blue stainings, immunohistochemical analysis, diffusion tensor imaging (DTI), and the assessment of blood-spinal cord barrier (BSCB) stability were performed. MSC treated animals exhibited gradual improvement in hind-limb locomotor function during the 4-week study period; however the vehicle-treated group displayed persistent motor deficits. In the MSC-treated group we observed the protection of white and gray matter volume reduction of axonal and neuronal loss or degeneration and preservation of microvasculature including BSCB function. Intravenous infusion of MSCs may provide therapeutic efficacy to improve functional outcomes in a rat model of severe iSCI via protection of white and gray matter.

DOI： 10.1016/j.brainres.2020.147040

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.wneu.2019.12.137

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.3171/2019.7.jns19575

PubMed

researchmap

Language：Japanese   Publisher：The Japanese Association of Rehabilitation Medicine  

Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I029914954

DOI： 10.2490/jjrmc.56.552

CiNii Research

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Cerebral small vessel disease (CSVD) is not only a cause of vascular dementia (VD) but also a contributing factor to Alzheimer's disease (AD). The essential pathological feature of CSVD is the disruption of blood-brain barrier (BBB). Dysfunction of BBB due to degeneration of both endothelial cells and pericytes in capillaries leads to neuronal damage and progressive brain atrophy. Moreover, deterioration of amyloid-β (Aβ) clearance due to the failure of the transvascular BBB transport system results in accumulation of Aβ in the brain. Intravenous infusion of mesenchymal stem cells (MSCs) elicits functional recovery in experimental models including stroke and spinal cord injury. One effect of MSCs is to restore disrupted BBB through remodeling of microvasculature. Using spontaneously hypertensive rats (stroke-prone) with impaired cognitive function as a CSVD model, we have shown that infused MSCs has a therapeutic effect for cognitive function. Restoration of BBB function via remodeling of microvasculature and inhibition of Aβ accumulation could inhibit progressive brain atrophy and lead to restore cognitive dysfunction. Gene expression analysis indicated that infused MSCs activates both transforming growth factor-β and angiopoietin 1 signaling pathways and promotes the remodeling of microvasculature. Thus, infused MSCs may represent a novel therapy for both VD and AD.

DOI： 10.1016/j.neuroscience.2019.04.018

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

DOI： 10.1016/j.ibror.2018.11.003

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Morbidity and mortality in patients with posterior circulation stroke remains an issue despite advances in acute stroke therapies. The intravenous infusion of mesenchymal stem cells (MSCs) elicits therapeutic efficacy in experimental supratentorial stroke models. However, since there are few reliable animal models of ischemia in the posterior circulation, the therapeutic approach with intravenous MSC infusion has not been tested. The objective of this study was to test the hypothesis that intravenously infused MSCs provide functional recovery in a newly developed model of brainstem infarction in rats.

METHODS: Basilar artery (BA) occlusion (BAO) was established in rats by selectively ligating 4 points of the proximal BA with 10-0 nylon monofilament suture. The intravenous infusion of MSCs was performed 1 day after BAO induction. MRI and histological examinations were performed to assess ischemic lesion volume, while multiple behavioral tests were performed to evaluate functional recovery.

RESULTS: The MSC-treated group exhibited a greater reduction in ischemic lesion volume, while behavioral testing indicated that the MSC-infused group had greater improvement than the vehicle group 28 days after the MSC infusion. Accumulated infused MSCs were observed in the ischemic brainstem lesion.

CONCLUSIONS: Infused MSCs may provide neuroprotection to facilitate functional outcomes and reduce ischemic lesion volume as evaluated in a newly developed rat model of persistent BAO.

DOI： 10.3171/2018.4.JNS173121

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE:
Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat models of cerebral infarction. Although clinical studies are ongoing, most studies have focused on the acute or subacute phase of stroke. In the present study, MSCs derived from bone marrow of rats were intravenously infused 8 weeks after the induction of a middle cerebral artery occlusion (MCAO) to investigate whether delayed systemic injection of MSCs improves functional outcome in the chronic phase of stroke in rats.

METHODS:
Eight weeks after induction of the MCAO, the rats were randomized and intravenously infused with either MSCs or vehicle. Ischemic volume and behavioral performance were examined. Blood-brain barrier (BBB) integrity was assessed by quantifying the leakage of Evans blue into the brain parenchyma after intravenous infusion. Immunohistochemical analysis was also performed to evaluate the stability of the BBB.

RESULTS:
Motor recovery was better in the MSC-treated group than in the vehicle-treated group, with rapid improvement (evident at 1 week post-infusion). In MSC-treated rats, reduced BBB leakage and increased microvasculature/repair and neovascularization were observed.

CONCLUSIONS:
These results indicate that the systemic infusion of MSCs results in functional improvement, which is associated with structural changes in the chronic phase of cerebral infarction, including in the stabilization of the BBB.

DOI： 10.3171/2018.5.JNS18140

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

DOI： 10.1016/j.brainres.2018.05.033

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

BACKGROUND: Recurrence is inevitable in glioblastomas (GBMs) and requires multifactorial processes. One of the factors that cause recurrence is the strong migratory capacity of GBM cells. We recently reported that actin, alpha, cardiac muscle 1 (ACTC1) could serve as a marker to detect GBM migration in clinical cases. OBJECTIVE: This study aimed to clarify whether the knockdown of highly expressed ACTC1 can inhibit the migratory capacity of cells in the GBM cell line. METHODS: ACTC1 expression was examined using immunocytochemistry and droplet digital polymerase chain reaction. The motility of GBM cells that were either treated with siRNA to knock down ACTC1 or untreated were investigated using a time-lapse study in vitro. RESULTS: The relatively high ACTC1 expression was confirmed in a GBM cell line, i.e., U87MG. The ACTC1 expression in U87MG cells was significantly inhibited by ACTC1-siRNA (p < 0.05). A cell movement tracking assay using time-lapse imaging demonstrated the inhibition of U87MG cell migration by ACTC1 knockdown. The quantitative cell migration analysis demonstrated that the distance traversed during 72 h was 3607 ± 458 (median ± SD) μm by untreated U87MG cells and 3570 ± 748 μm by negative control siRNA-treated cells. However, the distance migrated by ACTC1-siRNA-treated cells during 72 h was significantly shorter (1265 ± 457 μm, p < 0.01) than the controls. CONCLUSION: ACTC1 knockdown inhibits U87MG cell migration.

DOI： 10.1016/j.jns.2018.07.013

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.1089/neu.2018.5793

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.3171/2018.5.peds1845

PubMed

researchmap

Language：Japanese   Publisher：(公社)日本整形外科学会  

Ichushi

researchmap

Language：Japanese   Publisher：(公社)日本放射線技術学会  

Ichushi

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Edizioni Minerva Medica  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.23736/S0390-5616.16.03793-0

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1161/STROKEAHA.117.019216

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.esxm.2017.10.005

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.eplepsyres.2018.02.008

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Inc.  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.wneu.2017.12.166

PubMed

researchmap

Language：Japanese   Publisher：Japanese Society of Radiological Technology  

Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I029183540

DOI： 10.6009/jjrt.2018_JSRT_74.7.722

CiNii Research

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3171/2016.8.JNS16240

PubMed

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00701-017-3199-8

PubMed

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1007/s10143-016-0780-1

PubMed

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jocn.2016.12.023

PubMed

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.3171/2016.1.JNS152075

PubMed

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1073/pnas.1620641114

PubMed

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow elicits functional recovery in rat stroke models and clinical studies in patients are ongoing. Brain derived neurotrophic factor (BDNF) is a neurotrophic factor produced by MSCs and may contribute to their therapeutic efficacy. The purpose of the current study was to determine if BDNF is elevated in infarcted brain and in which compartment of blood (plasma or serum) after intravenous MSC infusion in a middle cerebral artery occlusion (MCAO) model in the rat. METHODS: In rats, a permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament and MSCs were intravenously administered 6 h after right MCAO induction. Enzyme-linked immunosorbent assay (ELISA) analysis of brain, serum and plasma BDNF were performed after the MSC infusion following the MCAO induction. Lesion volume was assessed using magnetic resonance imaging. Functional outcome was assessed using the Limb Placement Test. RESULTS: Infused MSCs reduced lesion volume and elicited functional improvement compared to the vehicle infused group. ELISA analysis of the MSC treated group revealed an increase BDNF levels in the infarcted hemisphere of the brain and plasma, but not in serum. The MSC group showed a greater increase in BDNF levels than sham control. In the MSC group, the expression of increased plasma BDNF levels correlated with increased brain BDNF levels. CONCLUSIONS: These results support the hypothesis that BDNF levels in plasma, but not serum, may be more appropriate to detect circulating BDNF in vivo following MSC infusion in a cerebral infarction rat model of ischemic stroke. Further, plasma BDNF might reflect in vivo functional viability of infused MSCs after stroke.

DOI： 10.23736/S0390-5616.17.03989-3

PubMed

researchmap

Language：English   Publishing type：Part of collection (book)   Publisher：Springer Japan  

DOI： 10.1007/978-4-431-56059-3_12

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2522/ptj.20150504

PubMed

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.neuroscience.2016.08.037

PubMed

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1007/s00701-016-2816-2

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1111/jsm.12957

PubMed

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.expneurol.2015.03.001

PubMed

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.neulet.2014.12.023

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.neulet.2014.10.039

Web of Science

researchmap

Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1002/glia.22583

Web of Science

researchmap

Language：Japanese   Publisher：The Japanese Society of Cerebral Blood Flow and Metabolism  

Several experimental and clinical studies have reported intravenous transplantation of mesenchymal stem cells (MSCs) derived from bone marrow ameliorates functional deficits in cerebral infarction. However, functional recovery is not always correlated with lesion volume assessed by T2 weighted image in MRI. In this study, we reported the relationship between fMRI patterns and functional recovery of ischemic stroke model rats transplanted intravenously MSCs. In medium infused group, electrical stimulation of the left forepaw elicited a unilateral (right cortex) activated signal detected by fMRI in the infarcted somatosensory cortex. In the MSCs infused group, their motor function were significantly improved compared to the medium infused group, and two fMRI patterns were observed: unilateral and bilateral activation of sensorimotor cortex. The bilateral activated pattern in the MSCs group showed the greatest functional recovery in spite of the same lesion volume compared to unilateral activated pattern. These results suggest that the detection of a bilateral signal in sensorimotor cortex by fMRI was more predictive of improved functional outcome than lesion volume alone. Further evaluation of these results in the ongoing randomize clinical trial (phase 3) using auto serum-expanded autologous MSCs in the stroke patients is warranted.

DOI： 10.16977/cbfm.25.2_67

CiNii Research

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.brainres.2012.12.028

Web of Science

researchmap

Language：Japanese   Publisher：(一社)日本救急医学会  

Ichushi

researchmap

Language：English  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.molmed.2012.02.003

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1371/journal.pone.0026577

Web of Science

researchmap

Language：English  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.expneurol.2011.01.010

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1155/2011/608496

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1002/glia.21026

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1523/JNEUROSCI.2769-09.2009

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1371/journal.pone.0007260

Web of Science

researchmap

Language：English  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.neulet.2008.08.093

Web of Science

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Methods in Molecular Biology  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1007/978-1-60327-931-4_13

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1002/glia.20718

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1682/JRRD.2007.03.0049

Web of Science

researchmap

Publishing type：Research paper (scientific journal)   Publisher：CNS Regeneration  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/B978-012373994-0.50020-8

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.ijdevneu.2007.02.002

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/S0079-6123(06)61030-3

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.brainres.2006.09.089

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1002/glia.20285

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1523/JNEUROSCI.3611-05.2006

Web of Science

researchmap

Language：English  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1523/JNEUROSCI.3611-05.2006

Web of Science

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Multiple Sclerosis as A Neuronal Disease  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/B978-012738761-1/50029-8

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1016/j.brainres.2004.09.062

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1523/JNEUROSCI.1998-04.2004

Web of Science

researchmap

Language：Japanese   Publisher：(株)メディカルレビュー社  

Ichushi

researchmap

Language：Japanese   Publisher：(株)中外医学社  

Ichushi

researchmap

Language：Japanese   Publisher：(株)最新医学社  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2003&ichushi_jid=J00516&link_issn=&doc_id=20030404050014&doc_link_id=issn%3D0370-8241%26volume%3D58%26issue%3D4%26spage%3D899&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0370-8241%26volume%3D58%26issue%3D4%26spage%3D899&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Ichushi

researchmap

Language：Japanese   Publisher：(株)最新医学社  

Ichushi

researchmap

Language：Japanese   Publisher：(株)三輪書店  

Ichushi

researchmap

Language：Japanese   Publisher：(一社)日本脳卒中学会  

Ichushi

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.1002/glia.1067

Web of Science

researchmap

Language：Japanese   Publisher：The Japan Stroke Society  

Polycystic kidney disease (PKD) is a genetic disorder characterized by the development of progressive cyst formation and enlargement in kidney. Cysts occur in the liver and other organs, and an association with various abnormalities of connective tissue has been reported, which changes include intracranial aneurysm, aortic dissection, and heart valve defects. Recently, the PKD 1 gene has been cloned and found to encode a 4303 amino acid protein, polycystin, which is thought to be involved in protein-protein and protein-carbohydrate interaction in the extracellular compartment. We have studied germline mutations in the PKD 1 gene by single-strand conformation polymorphism method and direct sequence analysis of genomic DNA from blood samples of 38 patients with cerebral aneurysms. In the present report, we demonstrate novel pathological mutations in two cerebral aneurysm patients who are not suffering from polycystic disease. These findings suggest PKD 1 mutation may play an important role in the development of cerebral aneurysm formation.

DOI： 10.3995/jstroke.22.457

CiNii Research

researchmap

Language：Japanese  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.11477/mf.1406901626

CiNii Research

PubMed

researchmap

Language：Japanese  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.11477/mf.1406901637

CiNii Research

PubMed

researchmap

Language：Japanese  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.11477/mf.1436901821

CiNii Research

Web of Science

researchmap

Language：Japanese  

Other Link： http://orcid.org/0000-0001-7961-9698

DOI： 10.11477/mf.1406901466

CiNii Research

PubMed

researchmap

Language：Japanese   Publisher：東京 : 医歯薬出版  

Other Link:： https://ndlsearch.ndl.go.jp/books/R000000004-I033152331

DOI： 10.32118/j02606.2024044254

CiNii Research

researchmap

Language：Japanese   Publisher：(株)総合医学社  

Ichushi

researchmap

Publisher：メジカルビュー社  

DOI： 10.18885/jjs.0000000915

CiNii Research

researchmap

Language：Japanese   Publisher：東京 : 日本整形外科学会  

Other Link:： https://ndlsearch.ndl.go.jp/books/R000000004-I031900016

CiNii Research

researchmap

Language：Japanese   Publisher：東京 : 日本整形外科学会  

Other Link:： https://ndlsearch.ndl.go.jp/books/R000000004-I031900040

CiNii Research

researchmap

Language：Japanese   Publisher：東京 : 先端医学社  

Other Link:： https://ndlsearch.ndl.go.jp/books/R000000004-I031697708

CiNii Research

researchmap

Language：Japanese   Publisher：[札幌] : 北海道外科学会  

Other Link:： http://id.ndl.go.jp/bib/031624318

CiNii Research

researchmap

Publisher：メジカルビュー社  

DOI： 10.18885/jjs.0000000561

CiNii Research

researchmap

Publisher：三輪書店  

DOI： 10.11477/mf.5002201508

CiNii Research

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

Ichushi

researchmap

Language：Japanese   Publisher：東京 : 全日本病院出版会  

Other Link:： https://ndlsearch.ndl.go.jp/books/R000000004-I030505357

CiNii Research

researchmap

Language：Japanese   Publisher：日本神経治療学会  

DOI： 10.15082/jsnt.37.3_314

CiNii Research

researchmap

Language：Japanese   Publisher：札幌 : 日本脳ドック学会  

Other Link:： https://ndlsearch.ndl.go.jp/books/R000000004-I030227371

CiNii Research

researchmap

Other Link:： https://ndlsearch.ndl.go.jp/books/R000000004-I029663888

DOI： 10.11477/mf.1552201630

CiNii Research

researchmap

Language：Japanese   Publisher：日本神経治療学会  

DOI： 10.15082/jsnt.36.6_s108

CiNii Research

researchmap

Language：Japanese   Publisher：東京 : 北隆館  

CiNii Research

researchmap

Other Link:： https://ndlsearch.ndl.go.jp/books/R000000004-I029303046

DOI： 10.18888/se.0000000641

CiNii Research

researchmap

Language：Japanese   Publisher：東京 : 日本整形外科学会  

Other Link:： https://ndlsearch.ndl.go.jp/books/R000000004-I029345982

CiNii Research

researchmap

Publisher：三輪書店  

DOI： 10.11477/mf.5002200894

CiNii Research

researchmap

Language：English   Publisher：日本脳神経CI学会  

Ichushi

researchmap

Language：Japanese   Publisher：日本脳循環代謝学会  

Ichushi

J-GLOBAL

researchmap

Language：Japanese   Publisher：(NPO)日本脳神経血管内治療学会  

Ichushi

researchmap

Language：English   Publisher：日本脳神経CI学会  

Ichushi

researchmap

Language：Japanese   Publisher：(公社)日本整形外科学会  

Ichushi

researchmap

Language：Japanese   Publisher：日本脳循環代謝学会  

DOI： 10.16977/cbfm.28.2_281

CiNii Research

Ichushi

J-GLOBAL

researchmap

Language：Japanese   Publisher：(公社)日本整形外科学会  

Ichushi

researchmap

Publisher：金原出版  

DOI： 10.18888/j00767.2017248117

CiNii Research

researchmap

Language：Japanese  

CiNii Research

researchmap

Language：Japanese   Publisher：(一社)日本移植学会  

Ichushi

researchmap

Language：Japanese   Publisher：(NPO)日本脳神経血管内治療学会  

Ichushi

J-GLOBAL

researchmap

Language：Japanese   Publisher：(NPO)日本脳神経血管内治療学会  

Ichushi

J-GLOBAL

researchmap

Language：Japanese   Publisher：(公社)日本理学療法士協会  

DOI： 10.14900/cjpt.2015.1063

CiNii Research

Ichushi

researchmap

Language：Japanese   Publisher：(公社)日本理学療法士協会  

DOI： 10.14900/cjpt.2015.1063

Ichushi

researchmap

Publisher：南江堂  

DOI： 10.15106/j00764.2016323715

CiNii Research

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese   Publisher：The Oto-Rhino-Laryngological Society of Japan, Inc.  

Other Link:： https://ndlsearch.ndl.go.jp/books/R000000004-I026196808

DOI： 10.3950/jibiinkoka.118.93

CiNii Research

researchmap

Other Link:： https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-25462227/

CiNii Research

researchmap

Language：Japanese  

Other Link:： http://search.jamas.or.jp/link/ui/2014228689

DOI： 10.11477/mf.1552110490

CiNii Research

researchmap

Language：Japanese   Publisher：日本脳循環代謝学会  

Ichushi

researchmap

Language：Japanese  

Other Link:： http://search.jamas.or.jp/link/ui/2013352161

CiNii Research

researchmap

Language：Japanese   Publisher：日本脳低温療法・体温管理学会  

Ichushi

researchmap

Language：Japanese   Publisher：大道学館出版部  

Other Link:： http://search.jamas.or.jp/link/ui/2013302524

CiNii Research

researchmap

CiNii Research

researchmap

Language：Japanese   Publisher：(一社)日本救急医学会  

Ichushi

researchmap

Language：Japanese  

Other Link:： http://search.jamas.or.jp/link/ui/2012334318

CiNii Research

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1016/j.neures.2009.09.613

Web of Science

researchmap

Language：Japanese  

CiNii Research

researchmap

Language：Japanese   Publisher：The Japan Stroke Society  

The adult brain has generally been thought to be incapable of significant self-repair. Recently, the adult mammalian brain has been shown to harbor neural stem cells that retain the potential for both neural production and differentiation in the experimental animal models. These findings offer the prospect of the potential use of neural stem cells for regenerative strategy. In the present report, the possible therapeutic strategy of the neural stem cell transplantation for the stroke is discussed.<BR>Self-renewing and multipotential properties of human neural stem cells were demonstrated in vitro. Histological examination of the ischemic lesion following transplantation revealed that the transplanted human neural stem cells differentiated into both neuronal and glial lineages. In addition, transplantation of neural stem cells into the stroke models resulted in the reduced ischemic volume. Behavior studies also demonstrated the functional benefits following transplantation. These findings reveal that human neural stem cells seem to be useful to establish a cell therapy for stroke.

DOI： 10.3995/jstroke.24.355

CiNii Research

J-GLOBAL

researchmap

CiNii Research

researchmap

Language：Japanese  

CiNii Research

researchmap

Language：Japanese  

CiNii Research

researchmap

Language：Japanese  

Other Link:： http://hdl.handle.net/10191/46062

CiNii Research

researchmap