Cabezas-Rodríguez Juan Antonio, Biarnes Carles, Martí-Navas Marian, Pineda Víctor, Comas-Cufí Marc, Pardo-Galiana Blanca, Zapata-Arriaza Elena, Piñero Pilar, Aguera-Morales Eduardo, Valverde Roberto, Ortega-Quintanilla Joaquín, Ainz-Gomez Leire, Baena-Palomino Pablo, Gutiérrez Isabel, Medina-Rodríguez Manuel, Ocete-Pérez Rafael, Gamero Miguel Angel, de Albóniga-Chindurza Asier, Hermosín Andrés, Aguilar-Pérez Marta, Villagran Diego, Escamilla-Gómez Virginia, Calderón-Cabrera Cristina, Nogueras Sonia, Jiménez Rosario, Martín Vanesa, Herrera Concha, Delgado Fernando, González Alejandro, Montaner Joan, Puig Josep, Moniche Francisco
Department of Neurology, Stroke Unit (J.A.C.-R., B.P.-G., L.A.-G., P.B.-P., M.M.-R., A.H., D.V., F.M.), Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
Department of Radiology (IDI) and Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, Spain (C.B., M.M.-N., V.P.).
Stroke. 2025 Aug;56(8):2198-2209. doi: 10.1161/STROKEAHA.124.050261. Epub 2025 Apr 30.
Bone marrow mononuclear cell (BM-MNC) intraarterial transplantation has emerged as a potential stroke therapy. We aimed to determine whether BM-MNC therapy induces changes in diffusion tensor imaging metrics of major white matter tracts.
The IBIS trial was an investigator-initiated multicenter, phase IIb, randomized, controlled, assessor-blinded, clinical trial. Seventy-seven patients (aged 18-80 years) with a nonlacunar middle cerebral artery ischemic stroke within 1 to 7 days from stroke onset and a National Institutes of Health Stroke Scale score of 6 to 20 were included. The primary outcome was the modified Rankin Scale score at 6 months. Among these participants, 38 patients (20 BM-MNCs-treated and 18 controls) had diffusion tensor imaging data available at both baseline and 6-month follow-up. Fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity for white matter tracts were obtained. We determined the average changes in diffusion tensor imaging-metric values over the follow-up period and correlated corticospinal tract integrity with clinical outcomes using Spearman´s correlation coefficient.
The mean (SD) age was 60.7 (14.01) years; 22 (57.9%) were men, and 31 (81.6%) underwent thrombectomy. The median (interquartile range) National Institutes of Health Stroke Scale score before randomization was 12 (9-15). Baseline diffusion tensor imaging metrics were comparable between groups. Fractional anisotropy values of patients treated with BM-MNC decreased significantly less throughout corticospinal tract ipsilateral to stroke lesion (-0.05 [95% CI, -0.07 to -0.03] versus -0.06 [95% CI, -0.09 to -0.04]; <0.0001) and the body of corpus callosum (-0.03 [95% CI, -0.01 to -0.07] versus -0.04 [95% CI, -0.02 to 0.08]; <0.0001]. Better preservation of the ipsilateral corticospinal tract measured with fractional anisotropy was significantly correlated with clinical outcomes (ie, modified Rankin Scale score [=-0.478], National Institutes of Health Stroke Scale score [=-0.594], Barthel index [=0.466] at 6 months [all <0.01]).
Intraarterial autologous BM-MNC transplantation within 7 days after stroke onset seems to modify long-term white matter tract microstructure, suggesting that this cell therapy may mitigate acute stroke damage, through main projection fibers. Greater corticospinal tract preservation was associated with improved clinical outcomes.
https://www.clinicaltrials.gov; Unique identifier: NCT02178657.
骨髓单个核细胞（BM-MNC）动脉内移植已成为一种潜在的中风治疗方法。我们旨在确定BM-MNC治疗是否会引起主要白质束扩散张量成像指标的变化。
IBIS试验是一项由研究者发起的多中心、IIb期、随机、对照、评估者盲法的临床试验。纳入77例年龄在18-80岁之间、中风发作后1至7天内发生非腔隙性大脑中动脉缺血性中风且美国国立卫生研究院卒中量表（NIHSS）评分为6至20分的患者。主要结局是6个月时的改良Rankin量表评分。在这些参与者中，38例患者（20例接受BM-MNC治疗和18例对照）在基线和6个月随访时均有扩散张量成像数据。获取白质束的各向异性分数、平均扩散率、轴向扩散率和径向扩散率。我们确定了随访期间扩散张量成像指标值的平均变化，并使用Spearman相关系数将皮质脊髓束完整性与临床结局进行关联。
平均（标准差）年龄为60.7（14.01）岁；22例（57.9%）为男性，31例（81.6%）接受了血栓切除术。随机分组前NIHSS评分的中位数（四分位间距）为12（9-15）。两组之间的基线扩散张量成像指标具有可比性。接受BM-MNC治疗的患者在中风病变同侧皮质脊髓束（-0.05 [95% CI，-0.07至-0.03] vs -0.06 [95% CI, -0.09至-0.04]；<0.0001）和胼胝体（-0.03 [95% CI，-0.01至-0.07] vs -0.04 [95% CI，-0.02至0.08]；<0.0001）的各向异性分数值下降明显较少。用各向异性分数测量的同侧皮质脊髓束的更好保存与临床结局显著相关（即6个月时的改良Rankin量表评分[=-0.478]、NIHSS评分[=-0.594]、Barthel指数[=0.466] [均<0.01]）。
中风发作后7天内进行动脉内自体BM-MNC移植似乎可改变长期白质束微观结构，表明这种细胞治疗可能通过主要投射纤维减轻急性中风损伤。皮质脊髓束保存得更好与临床结局改善相关。
