Abstract 45: Intracerebral Transplantation of Autologous Bone Marrow Stem Cell (BMSC) Against Acute Ischemic Stroke, Preliminary Data of Phase 1 Clinical Trial (RAINBOW Project)

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Masahito Kawabori ◽  
Hideo Shichinohe ◽  
Satoshi Kuroda ◽  
Kiyohiro Houkin

Background: Recent breakthrough in cell therapy is expected to reverse the neurological sequelae of stroke. Prior studies have demonstrated that bone marrow stromal cells (BMSC) have therapeutic potential against stroke. In this study, we investigated the use of autologous BMSC transplantation for acute ischemic stroke through direct transplantation route with several new aspects including cell labeling and tracking, socioecomonic analysis using QALY, and the use of human platelet lysate (PL) instead of fetal bovine serum. This study is called the Research on Advanced Intervention using Novel Bone marrOW stem cell (RAINBOW, UNIN ID: UMIN000026130). Methods/Design: RAINBOW is a phase 1, open-label, uncontrolled, dose-response study, with the primary aim to determine the safety of the autologous BMSC administered to the patients with acute ischemic stroke. Estimated enrollment is 7 patients suffering severe neurological deficits. Approximately 50 mL of the bone marrow is extracted from the iliac bone of each patient 15 days or later from the onset, and BMSCs are cultured with allogeneic PL and are labeled with superparamagnetic iron oxide for cell tracking using magnetic resonance imaging (MRI). BMSCs are stereotactically administered around the area of infarction in the subacute phase. Each patient will be administered a dose of 20 or 50 million cells. Neurological scoring, MRI for cell tracking, 18 F-fuorodeoxyglucose positron emission tomography, and 123 I-Iomazenil single photon emission computed tomography will be performed throughout 1 year after the administration. Results: 6 patients have successfully finished cell transplantation, and there was no severe adverse event in any of the patient during surgical and follow-up period. Favorable motor recoveries are seen in 5 of 6 patients, and cell engraftment and migration to ischemic site was also observed by magnetic resonance imaging. Discussion: This is a first-in-human trial to use labelled BMSC to the patients with acute ischemic stroke. Intracerebral transplantation of autologous BMSC is safe and well tolerated. Moreover, it is expected that the bio-imaging techniques can clarify the therapeutic mechanisms.

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Masahito Kawabori ◽  
Hideo Shichinohe ◽  
Satoshi Kuroda ◽  
Kiyohiro Houkin

Background: Recent breakthrough in cell therapy is expected to reverse the neurological sequelae of stroke. We investigated the safety and feasibility of intracerebral transplantation of autologous BMSC in the subacute phase of stroke (RAINBOW trial). Several new aspects including cell labeling and tracking, socioecomonic analysis using QALY, and the use of human platelet lysate instead of fetal bovine serum were adopted. (UNIN ID: UMIN000026130) Methods/Design: This is a phase 1, open-label, uncontrolled, dose-response study enrolling adults with severe motor deficits (mRS>3) 14 days after stroke. Approximately 50 mL of the bone marrow is extracted from the iliac bone of each patient 15 days or later from the onset, and BMSCs are cultured with allogeneic human platelet lysate (PL) and are labeled with superparamagnetic iron oxide for cell tracking using MRI. BMSCs are stereotactically administered around the area of infarction approximately 2 months from the ischemic stroke. Each patient will be administered a dose of 20 or 50 million cells. Neurological scoring, MRI for cell tracking, 18 F-fuorodeoxyglucose positron emission tomography, and 123 I-Iomazenil single photon emission computed tomography will be performed throughout 1 year after the administration. Results: All 7 patients have been successfully finished transplantation, and there was no severe adverse event in any of the patient regarding the surgical procedure nor cell quality. Favorable motor recoveries (change in mRS > 1) are seen in 5 of 7 patients, and cell engraftment and migration to ischemic site was also observed. Discussion: This is a first-in-human trial to use labelled BMSC to the patients with subacute ischemic stroke. Intracerebral transplantation of autologous BMSC is safe and well tolerated. Cell migration to the ischemic boundary can clarify the therapeutic mechanisms.


2002 ◽  
Vol 42 (7) ◽  
pp. 281-288
Author(s):  
Keisuke MARUYAMA ◽  
Tsuneyoshi EGUCHI ◽  
Shigeo SORA ◽  
Masafumi IZUMI ◽  
Hirofumi HIYAMA ◽  
...  

Stroke ◽  
2017 ◽  
Vol 48 (5) ◽  
pp. 1241-1247 ◽  
Author(s):  
Karl Georg Haeusler ◽  
Christian Wollboldt ◽  
Laura zu Bentheim ◽  
Juliane Herm ◽  
Sebastian Jäger ◽  
...  

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Xiangyan Chen ◽  
Lu Zheng ◽  
Jia LI ◽  
Wenjie Yang

Backgrounds: The purpose of this study was to investigate vessel wall features visualization by high resolution magnetic resonance imaging (HRMRI) in a series of ischemic stroke patients and to identify differences between lesions in the anterior and posterior circulation. Methods: We consecutively recruited Chinese patients with acute ischemic stroke or transient ischemic attack from 2016 to 2018. All patients were scanned at 3T magnetic resonance imaging. We evaluated pre-and post-contrast cross-sectional views of M1 and M2 segments of middle cerebral arteries (MCAs), basilar arteries (BA) and V4 segments of vertebral arteries (VAs). Results: A total of 74 patients (males 52.3%; median age 62 years old) were included in this study, among which, 234 lesions were identified on HRMRI, including 117 MCA lesions, 26 BA lesions, and 91 VA lesions. The sensitivity and specificity of MRA for diagnosing stenosis in anterior circulation were 89.3% (95% CI, 81.8%- 94.2%) and 50.0 (95% CI, 9.2%- 90.8%). The sensitivity and specificity of MRA for diagnosing stenosis in posterior circulation were 73.2% (95% CI, 63.9%- 80.9%) and 40.0 (95% CI, 7.3%- 83.0%). VA had a significantly higher contrast enhancement index (43.71± 7.74, p <0.016) than MCA (23.32± 2.46) or BA (22.69± 5.31) . Anterior circulation plaques had higher degree of stenosis (anterior versus posterior: 68.5% vs. 62.9%, p =0.036), more eccentric distribution (anterior versus posterior: 70.1% versus 53.8%, p =0.015) and higher rate of intraplaque hemorrhage (anterior versus posterior: 17.1% versus 7.7%, p =0.046). The plaques in posterior circulation had a thicker lesion wall (posterior versus anterior 16.58± 8.25 mm 2 vs. 9.10± 4.07 mm 2 , p <0.001) and higher enhancement index (posterior versus anterior 39.04± 8.50 vs. 23.32± 2.46, p <0.001) than the plaques in anterior circulation. Conclusions: The lesions in posterior circulations could be obscure on MRA. The area stenosis, intraplaque hemorrhage and enhancement index differed between circulations.


Stroke ◽  
2020 ◽  
Vol 51 (7) ◽  
pp. 2240-2243
Author(s):  
Zien Zhou ◽  
Sohei Yoshimura ◽  
Candice Delcourt ◽  
Richard I. Lindley ◽  
Shoujiang You ◽  
...  

Background and Purpose: To determine factors associated with fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on magnetic resonance imaging and their prognostic significance in thrombolysis-treated patients with acute ischemic stroke from the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) trial alteplase-dose arm. Methods: Patients with acute ischemic stroke (N=293) with brain magnetic resonance imaging (FLAIR and diffusion-weighted imaging sequences) scanned <4.5 hours of symptom onset were assessed for location and extent (score) of FLAIR-HAs, infarct volume, large vessel occlusion (LVO), and other ischemic signs. Logistic regression models were used to determine predictors of FLAIR-HAs and the association of FLAIR-HAs with 90-day outcomes: favorable functional outcome (primary; modified Rankin Scale scores, 0–1), other modified Rankin Scale scores, and intracerebral hemorrhage. Results: Prior atrial fibrillation, LVO, large infarct volume, and anterior circulation infarction were independently associated with FLAIR-HAs. The rate of modified Rankin Scale scores 0 to 1 was numerically lower in patients with FLAIR-HAs versus without (69/152 [45.4%] versus 75/131 [57.3%]), as was the subset of LVO (37/93 [39.8%] versus 9/16 [56.3%]), but not in those without LVO (25/36 [69.4%] versus 60/106 [56.6%]). After adjustment for covariables, FLAIR-HAs were independently associated with increased primary outcome (adjusted odds ratio [95% CI]: overall 4.14 [1.63–10.50]; with LVO 4.92 [0.87–27.86]; no LVO 6.16 [1.57–24.14]) despite an increased risk of hemorrhagic infarct (4.77 [1.12–20.26]). Conclusions: FLAIR-HAs are more frequent in acute ischemic stroke with cardioembolic features and indicate potential for a favorable prognosis in thrombolysis-treated patients possibly mediated by LVO. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01422616.


Stroke ◽  
2014 ◽  
Vol 45 (8) ◽  
pp. 2330-2334 ◽  
Author(s):  
Sarah Power ◽  
Charles Matouk ◽  
Leanne K. Casaubon ◽  
Frank L. Silver ◽  
Timo Krings ◽  
...  

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