Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis.
Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis.
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DOI：
10.1186/s13024-017-0227-3
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发表时间：
2017-11-13
影响因子：
15.1
通讯作者：
Mead RJ
中科院分区：
文献类型：
--
作者：
Ciervo Y;Ning K;Jun X;Shaw PJ;Mead RJ
肌萎缩性侧索硬化症（ALS）是一种快速进展的神经退行性疾病，大脑和脊髓内运动神经元的丧失导致肌肉萎缩、无力、瘫痪，并在症状出现后3-5年内最终死亡。疾病病理背后的特定分子机制尚不完全清楚，神经保护治疗方案的效果最低。近年来，干细胞移植作为一种治疗ALS患者的新方法得到了广泛的研究，成为一个激烈而有争议的研究领域。在几项使用SOD1G93A ALS小鼠模型的临床前研究中，干细胞被证明具有神经保护作用，有效地延迟疾病发作和延长生存期。尽管干细胞技术取得了长足的进步，临床前研究也取得了可喜的成果，但仍有几个问题未得到解答，如确定最合适和有益的细胞来源、细胞剂量、给药途径和治疗机制。本综述将涵盖该领域的出版物，全面讨论干细胞在ALS治疗潜力方面的进展、挑战和未来方向，重点是间充质干细胞。综上所述，鉴于其高增殖活性、免疫调节、多分化潜能和分泌神经保护因子的能力，成体间充质干细胞是临床转化的一个有希望的候选者。然而，诸如最佳剂量、分化状态、给药途径和潜在的潜在治疗机制等技术障碍仍需评估。
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition where loss of motor neurons within the brain and spinal cord leads to muscle atrophy, weakness, paralysis and ultimately death within 3–5 years from onset of symptoms. The specific molecular mechanisms underlying the disease pathology are not fully understood and neuroprotective treatment options are minimally effective. In recent years, stem cell transplantation as a new therapy for ALS patients has been extensively investigated, becoming an intense and debated field of study. In several preclinical studies using the SOD1G93A mouse model of ALS, stem cells were demonstrated to be neuroprotective, effectively delayed disease onset and extended survival. Despite substantial improvements in stem cell technology and promising results in preclinical studies, several questions still remain unanswered, such as the identification of the most suitable and beneficial cell source, cell dose, route of delivery and therapeutic mechanisms. This review will cover publications in this field and comprehensively discuss advances, challenges and future direction regarding the therapeutic potential of stem cells in ALS, with a focus on mesenchymal stem cells. In summary, given their high proliferation activity, immunomodulation, multi-differentiation potential, and the capacity to secrete neuroprotective factors, adult mesenchymal stem cells represent a promising candidate for clinical translation. However, technical hurdles such as optimal dose, differentiation state, route of administration, and the underlying potential therapeutic mechanisms still need to be assessed.
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DOI：
10.1126/science.aaa3650
发表时间：
2015-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cirulli ET;Lasseigne BN;Petrovski S;Sapp PC;Dion PA;Leblond CS;Couthouis J;Lu YF;Wang Q;Krueger BJ;Ren Z;Keebler J;Han Y;Levy SE;Boone BE;Wimbish JR;Waite LL;Jones AL;Carulli JP;Day-Williams AG;Staropoli JF;Xin WW;Chesi A;Raphael AR;McKenna-Yasek D;Cady J;Vianney de Jong JM;Kenna KP;Smith BN;Topp S;Miller J;Gkazi A;FALS Sequencing Consortium;Al-Chalabi A;van den Berg LH;Veldink J;Silani V;Ticozzi N;Shaw CE;Baloh RH;Appel S;Simpson E;Lagier-Tourenne C;Pulst SM;Gibson S;Trojanowski JQ;Elman L;McCluskey L;Grossman M;Shneider NA;Chung WK;Ravits JM;Glass JD;Sims KB;Van Deerlin VM;Maniatis T;Hayes SD;Ordureau A;Swarup S;Landers J;Baas F;Allen AS;Bedlack RS;Harper JW;Gitler AD;Rouleau GA;Brown R;Harms MB;Cooper GM;Harris T;Myers RM;Goldstein DB
通讯作者：
Goldstein DB
影响因子：
6.1
作者：
Cabanes, Carmen;Bonilla, Sonia;Martinez, Salvador
通讯作者：
Martinez, Salvador
影响因子：
9.9
作者：
Alexianu, ME;Kozovska, M;Appel, SH
通讯作者：
Appel, SH
影响因子：
3.9
作者：
Abel, Olubunmi;Powell, John F.;Al-Chalabi, Ammar
通讯作者：
Al-Chalabi, Ammar
影响因子：
4.5
作者：
Boido, Marina;Piras, Antonio;Vercelli, Alessandro
通讯作者：
Vercelli, Alessandro