Phase I Trial of Repeated Intrathecal Autologous Bone Marrow-Derived Mesenchymal Stromal Cells in Amyotrophic Lateral Sclerosis

被引:134
作者
Oh, Ki-Wook [1 ,2 ]
Moon, Chanil [2 ]
Kim, Hyun Young [1 ]
Oh, Sung-Il [2 ,3 ]
Park, Jinseok [1 ,2 ]
Lee, Jun Ho [4 ]
Chang, In Young [4 ]
Kim, Kyung Suk [4 ]
Kim, Seung Hyun [1 ,2 ]
机构
[1] Hanyang Univ Hosp, Coll Med, Dept Neurol, Seoul, South Korea
[2] Hanyang Univ Hosp, Cell Therapy Ctr Neurol Disorders, Seoul, South Korea
[3] Inje Univ, Coll Med, Busan Paik Hosp, Dept Neurol, Busan, South Korea
[4] Corestem Inc, Bioengn Inst, Seoul, South Korea
关键词
Amyotrophic lateral sclerosis; Clinical trials; Mesenchymal stromal cells; Intrathecal; TRANSGENIC MOUSE MODEL; BLOOD STEM-CELLS; CLINICAL-TRIALS; TRANSPLANTATION; PROGRESSION; SAFETY; INJECTION; MICE;
D O I
10.5966/sctm.2014-0212
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Stem cell therapy is an emerging alternative therapeutic or disease-Modifying strategy for amyotrophic lateral sclerosis (ALS). The aim of this open-label phase I clinical trial was to evaluate the safety of two repeated intrathecal injections of autologous. bone marrow (BM)-derived mesenchymal stromal cells (MSCs) in ALS patients. Eight patients with definite or probable ALS were enrolled. After a 3-month lead-in period, autologous MSCs were isolated two times from the BM at an interval of 26 days and were then expanded in vitro for 28 days and suspended in autologous cerebrospinal fluid. Of the 8 patients, 7 received 2 intrathecal injections of a utologous MSCs (1 x 10(6) cells per kg) 26 days apart. Clinical or laboratory measurements were recorded to evaluate the safety 12 months after the first MSC injection. The ALS Functional Rating Scale-Revised (ALSFRS-R), the Appel ALS score, and forced vital capacity were used to evaluate the patients' disease status. One patient died before treatment and was withdrawn from the study. With the exception of that patient, no-serious adverse events were observed during the 12-month follow-up period. Most of the adverse events were self-limited or subsided after supportive treatment within 4 days. Decline in the ALSFRS-R score was not accelerated during the 6-month follow-up period. Two repeated intrathecal injections of autologous MSCs were safe and feasible throughout the duration of the 12-month follow-up period.
引用
收藏
页码:590 / 597
页数:8
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