Migration and homing of bone-marrow mononuclear cells in chronic ischemic stroke after intra-arterial injection
Migration and homing of bone-marrow mononuclear cells in chronic ischemic stroke after intra-arterial injection
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DOI：
10.1016/j.expneurol.2009.10.010
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发表时间：
2010-01-01
影响因子：
5.3
通讯作者：
de Freitas, Gabriel R.
中科院分区：
文献类型：
--
作者：
Barbosa da Fonseca, Lea Mirian;Gutfilen, Bianca;de Freitas, Gabriel R.
基于细胞的治疗一直被认为是治疗神经系统疾病的一种有前途的治疗方法。然而，目前还没有临床可用的方法来监测移植的细胞是否到达并保留在大脑中。本研究探讨了~(99)Tc标记的自体骨髓单个核细胞(BMMC)在慢性缺血性卒中细胞治疗临床研究中检测其分布和归巢的可行性。6例男性患者，年龄24~65岁，大脑中动脉(MCA)内缺血性脑梗塞(MCA)59~82天。细胞剂量范围为1.25×10(8)~5×10(8)。大约2×10(7)个细胞被~(99)m标记，并与未标记的细胞一起通过导管导航到大脑中动脉。在120天的随访中，所有患者都没有出现任何并发症。全身核素扫描显示，所有患者在2小时后脑内细胞归巢，而剩余的摄取主要分布在肝、肺、脾、肾和膀胱。此外，单光子发射计算机断层扫描(SPECF)在2小时时的摄取定量显示，所有患者的脑内放射性优先聚集在受缺血梗塞影响的半球。然而，在24小时时，仅有2例患者在大脑中可分辨出归巢，而所有患者的其他器官仍可见摄取。综上所述，这些结果表明，用99m标记骨髓基质细胞是一种安全可行的技术，可以至少24小时监测动脉内移植细胞的迁移和植入。(C)2009 Elsevier Inc.版权所有。
Cell-based treatments have been considered a promising therapy for neurological diseases. However, currently there are no clinically available methods to monitor whether the transplanted cells reach and remain in the brain. In this study we investigated the feasibility of detecting the distribution and homing of autologous bone-marrow mononuclear cells (BMMCs) labeled with Technetium-99 m (Tc-99m) in a cell-based therapy clinical study for chronic ischemic stroke. Six male patients (ages 24-65 years) with ischemic cerebral infarcts within the middle cerebral artery (MCA) between 59 and 82 days were included. Cell dose ranged from 1.25 x 10(8) to 5 x 10(8). Approximately 2 x 10(7) cells were labeled with Tc-99m and intra-arterially delivered together with the unlabeled cells via a catheter navigated to the MCA. None of the patients showed any complications on the 120-day follow-up. Whole body scintigraphies indicated cell homing in the brain of all patients at 2 h, while the remaining uptake was mainly distributed to liver, lungs, spleen, kidneys and bladder. Moreover, quantification of uptake in Single-Photon Emission Computed Tomography (SPECF) at 2 h showed preferential accumulation of radioactivity in the hemisphere affected by the ischemic infarct in all patients. However, at 24 h homing could only distinguished in the brains of 2 patients, while in all patients uptake was still seen in the other organs. Taken together, these results indicate that labeling of BMMCs with Tc-99m is a safe and feasible technique that allows monitoring the migration and engraftment of intra-arterially transplanted cells for at least 24 h. (C) 2009 Elsevier Inc. All rights reserved.