Clinical safety of intrathecal administration of mesenchymal stromal cell-derived neural progenitors in multiple sclerosis
Clinical safety of intrathecal administration of mesenchymal stromal cell-derived neural progenitors in multiple sclerosis
复制标题
DOI：
10.1016/j.jcyt.2016.08.007
复制
发表时间：
2016-12-01
期刊：
影响因子：
4.5
通讯作者：
Sadiq, Saud A.
中科院分区：
文献类型：
--
作者：
Harris, Violaine K.;Vyshkina, Tamara;Sadiq, Saud A.
背景目标。存在开发用于脱髓鞘疾病多发性硬化（MS）的再生疗法的关键未满足的需求。我们先前表征了来自骨髓间充质基质细胞（MSC-NPs）的神经祖细胞的免疫调节和营养特性，并确定来自MS和非MS患者的细胞同样具有治疗活性。在MS的实验模型中，鞘内MSC-NP注射导致疾病改善，T细胞浸润减少，并且与向炎症部位募集常驻祖细胞相关的病变病理学不太严重。在这项初步可行性研究中，我们研究了6例MS患者鞘内MSC-NP治疗的安全性和剂量。所有其他常规MS治疗均难治的进展性MS和晚期残疾患者入组本研究。对于每个剂量，从自体MSC培养MSC-NP细胞，并在鞘内给药前进行质量控制测试。对患者的不良事件和神经系统状态进行评价，以评估治疗的安全性。结果6例进行性MS患者接受了2 - 5次递增剂量自体MSC-NP鞘内注射治疗，并在首次注射后平均随访7.4年。没有发现安全性问题，没有严重不良事件，多次给药方案耐受良好。6例患者中有4例在MSC-NP治疗后显示出可测量的临床改善。讨论这项初步研究支持MS自体MSC-NP治疗的初步首次人体安全性和耐受性。
Background aims. There is a critical unmet need to develop regenerative therapies for the demyelinating disease multiple sclerosis (MS). We previously characterized the immunoregulatory and trophic properties of neural progenitors derived from bone marrow mesenchymal stromal cells (MSC-NPs) and established that cells derived from MS and non-MS patients alike were therapeutically viable. In an experimental model of MS, intrathecal MSC-NP injection resulted in disease amelioration with decreased T-cell infiltration, and less severe lesion pathology associated with recruitment of resident progenitors to inflammatory sites. In this pilot feasibility study, we investigated safety and dosing of intrathecal MSC-NP therapy in six patients with MS. Methods. Patients with progressive MS and advanced disability who were refractory to all other conventional MS treatments were enrolled in the study. For each dose, MSC-NP cells were cultured from autologous MSCs and tested for quality control before intrathecal administration. Patients were evaluated for adverse events and neurological status to assess safety of the treatment. Results. Six patients with progressive MS were treated with between 2 and 5 intrathecal injections of escalating doses of autologous MSC-NPs and were followed an average of 7.4 years after initial injection. There were no safety concerns noted, no serious adverse events, and the multiple dosing regimen was well tolerated. Four of the six patients showed a measurable clinical improvement following MSC-NP treatment. Discussion. This pilot study supports preliminary first-in-human safety and tolerability of autologous MSC-NP treatment for MS.