干细胞治疗肌肉萎缩症。
Stem cell therapy for muscular dystrophies.
机构信息
Department of Cellular, Computational and Integrative Biology (CIBIO) and.
Dulbecco Telethon Institute, University of Trento, Povo, Italy.
出版信息
J Clin Invest. 2020 Nov 2;130(11):5652-5664. doi: 10.1172/JCI142031.
Abstract
Muscular dystrophies are a heterogeneous group of genetic diseases, characterized by progressive degeneration of skeletal and cardiac muscle. Despite the intense investigation of different therapeutic options, a definitive treatment has not been developed for this debilitating class of pathologies. Cell-based therapies in muscular dystrophies have been pursued experimentally for the last three decades. Several cell types with different characteristics and tissues of origin, including myogenic stem and progenitor cells, stromal cells, and pluripotent stem cells, have been investigated over the years and have recently entered in the clinical arena with mixed results. In this Review, we do a roundup of the past attempts and describe the updated status of cell-based therapies aimed at counteracting the skeletal and cardiac myopathy present in dystrophic patients. We present current challenges, summarize recent progress, and make recommendations for future research and clinical trials.
摘要
肌肉萎缩症是一组异质性的遗传疾病，其特征是骨骼肌和心肌进行性退化。尽管对不同的治疗选择进行了深入研究，但对于这种衰弱性病理类别仍未开发出明确的治疗方法。在过去的三十年中，肌肉萎缩症的细胞疗法一直在进行实验研究。多年来，已经研究了多种具有不同特性和起源组织的细胞类型，包括肌源性干细胞和祖细胞、基质细胞和多能干细胞，并已将其应用于临床，取得了不同的结果。在这篇综述中，我们总结了过去的尝试，并描述了旨在对抗肌肉萎缩症患者骨骼和心肌病变的基于细胞的治疗方法的最新进展。我们提出了当前的挑战，总结了最近的进展，并为未来的研究和临床试验提出了建议。
相似文献
1
Stem cell therapy for muscular dystrophies.干细胞治疗肌肉萎缩症。
J Clin Invest. 2020 Nov 2;130(11):5652-5664. doi: 10.1172/JCI142031.
2
Stem cell therapies to treat muscular dystrophy: progress to date.干细胞疗法治疗肌肉萎缩症：迄今为止的进展。
BioDrugs. 2010 Aug 1;24(4):237-47. doi: 10.2165/11534300-000000000-00000.
3
Concise review: stem cell therapy for muscular dystrophies.简明综述：干细胞疗法治疗肌肉萎缩症。
Stem Cells Transl Med. 2012 Nov;1(11):833-42. doi: 10.5966/sctm.2012-0071. Epub 2012 Oct 23.
4
Generation of human myogenic progenitors from pluripotent stem cells for in vivo regeneration.从多能干细胞生成人类肌源性祖细胞用于体内再生。
Cell Mol Life Sci. 2022 Jul 8;79(8):406. doi: 10.1007/s00018-022-04434-8.
5
Cellular Therapies for Muscular Dystrophies: Frustrations and Clinical Successes.用于治疗肌肉萎缩症的细胞疗法：挫折与临床成功案例
Hum Gene Ther. 2016 Feb;27(2):117-26. doi: 10.1089/hum.2015.139. Epub 2016 Jan 25.
6
Pluripotent Stem Cell-Based Therapeutics for Muscular Dystrophies.基于多能干细胞的肌肉疾病治疗方法。
Trends Mol Med. 2019 Sep;25(9):803-816. doi: 10.1016/j.molmed.2019.07.004.
7
Generation of skeletal muscle cells from embryonic and induced pluripotent stem cells as an in vitro model and for therapy of muscular dystrophies.胚胎和诱导多能干细胞生成骨骼肌细胞作为体外模型及用于治疗肌肉疾病。
J Cell Mol Med. 2012 Jul;16(7):1353-64. doi: 10.1111/j.1582-4934.2011.01498.x.
8
Stem cell therapies for muscle disorders.肌肉疾病的干细胞疗法。
Curr Opin Neurol. 2012 Oct;25(5):597-603. doi: 10.1097/WCO.0b013e328357f288.
9
Stem cell-based therapies for Duchenne muscular dystrophy.基于干细胞的杜氏肌营养不良症疗法。
Exp Neurol. 2020 Jan;323:113086. doi: 10.1016/j.expneurol.2019.113086. Epub 2019 Oct 19.
10
Muscle Stem/Progenitor Cells and Mesenchymal Stem Cells of Bone Marrow Origin for Skeletal Muscle Regeneration in Muscular Dystrophies.肌肉干细胞/祖细胞和骨髓来源的间充质干细胞在肌肉疾病中的骨骼肌再生。
Arch Immunol Ther Exp (Warsz). 2018 Oct;66(5):341-354. doi: 10.1007/s00005-018-0509-7. Epub 2018 Mar 13.
引用本文的文献
1
Role of Perinatal Stem Cell Secretome as Potential Therapy for Muscular Dystrophies.围产期干细胞分泌组作为肌肉萎缩潜在治疗方法的作用
Biomedicines. 2025 Feb 13;13(2):458. doi: 10.3390/biomedicines13020458.
2
Implantation of Autologous Skeletal Muscle-Derived Cells Combined with Electrical Stimulation in Patients with Stress Urinary Incontinence.自体骨骼肌来源细胞植入联合电刺激治疗压力性尿失禁患者
Int Urogynecol J. 2025 Mar;36(3):703-713. doi: 10.1007/s00192-025-06079-0. Epub 2025 Feb 20.
3
HMGB1 in Septic Muscle Atrophy: Roles and Therapeutic Potential for Muscle Atrophy and Regeneration.高迁移率族蛋白B1在脓毒症性肌肉萎缩中的作用及对肌肉萎缩和再生的治疗潜力
J Cachexia Sarcopenia Muscle. 2025 Feb;16(1):e13711. doi: 10.1002/jcsm.13711.
4
Efficacy of Cystic Fibrosis Transmembrane Regulator Corrector C17 in Beta-Sarcoglycanopathy-Assessment of Patient's Primary Myotubes.囊性纤维化跨膜调节因子校正剂C17在β-肌聚糖病中的疗效——患者原代肌管评估
Int J Mol Sci. 2024 Dec 11;25(24):13313. doi: 10.3390/ijms252413313.
5
Gene-editing in patient and humanized-mice primary muscle stem cells rescues dysferlin expression in dysferlin-deficient muscular dystrophy.在患者和人源化小鼠的原代肌肉干细胞中进行基因编辑可挽救dysferlin缺乏型肌营养不良症中dysferlin的表达。
Nat Commun. 2025 Jan 2;16(1):120. doi: 10.1038/s41467-024-55086-0.
6
Precision genome editing using combinatorial viral vector delivery of CRISPR-Cas9 nucleases and donor DNA constructs.利用组合病毒载体递送CRISPR-Cas9核酸酶和供体DNA构建体进行精准基因组编辑。
Nucleic Acids Res. 2025 Jan 11;53(2). doi: 10.1093/nar/gkae1213.
7
Hypoxia-induced PD-L1 expression and modulation of muscle stem cell allograft rejection.缺氧诱导的程序性死亡配体1（PD-L1）表达与肌肉干细胞同种异体移植排斥反应的调节
Front Pharmacol. 2024 Nov 1;15:1471563. doi: 10.3389/fphar.2024.1471563. eCollection 2024.
8
Exosomes in the pathogenesis and treatment of cancer-related cachexia.外泌体在癌症恶病质发病机制和治疗中的作用。
J Transl Med. 2024 Apr 30;22(1):408. doi: 10.1186/s12967-024-05201-y.
9
Amelioration of Morphological Pathology in Cardiac, Respiratory, and Skeletal Muscles Following Intraosseous Administration of Human Dystrophin Expressing Chimeric (DEC) Cells in Duchenne Muscular Dystrophy Model.在杜兴氏肌营养不良模型中，经骨内注射表达人抗肌萎缩蛋白的嵌合细胞（DEC）后，心脏、呼吸和骨骼肌形态病理学的改善
Biomedicines. 2024 Mar 6;12(3):586. doi: 10.3390/biomedicines12030586.
10
Cell-mediated exon skipping normalizes dystrophin expression and muscle function in a new mouse model of Duchenne Muscular Dystrophy.细胞介导的外显子跳跃可使一种新型杜氏肌营养不良症小鼠模型中的抗肌萎缩蛋白表达和肌肉功能正常化。
EMBO Mol Med. 2024 Apr;16(4):927-944. doi: 10.1038/s44321-024-00031-3. Epub 2024 Mar 4.
本文引用的文献
1
Extracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping.用于包装 CRISPR-Cas9 蛋白和 sgRNA 的细胞外纳米囊泡，以诱导治疗性外显子跳跃。
Nat Commun. 2020 Mar 13;11(1):1334. doi: 10.1038/s41467-020-14957-y.
2
Muscular dystrophies.肌肉萎缩症。
Lancet. 2019 Nov 30;394(10213):2025-2038. doi: 10.1016/S0140-6736(19)32910-1.
3
Screening identifies small molecules that enhance the maturation of human pluripotent stem cell-derived myotubes.筛选鉴定出能增强人多能干细胞来源肌管成熟的小分子。
Elife. 2019 Nov 11;8:e47970. doi: 10.7554/eLife.47970.
4
Core Transcription Factors Promote Induction of PAX3-Positive Skeletal Muscle Stem Cells.核心转录因子促进 PAX3 阳性骨骼肌干细胞的诱导。
Stem Cell Reports. 2019 Aug 13;13(2):352-365. doi: 10.1016/j.stemcr.2019.06.006. Epub 2019 Jul 25.
5
What is the level of dystrophin expression required for effective therapy of Duchenne muscular dystrophy?对于杜氏肌营养不良症的有效治疗，需要达到什么样的肌营养不良蛋白表达水平？
J Muscle Res Cell Motil. 2019 Jun;40(2):141-150. doi: 10.1007/s10974-019-09535-9. Epub 2019 Jul 9.
6
Therapeutic developments for Duchenne muscular dystrophy.杜氏肌营养不良症的治疗进展。
Nat Rev Neurol. 2019 Jul;15(7):373-386. doi: 10.1038/s41582-019-0203-3.
7
Disease-modifying bioactivity of intravenous cardiosphere-derived cells and exosomes in mdx mice.静脉注射心肌球来源细胞和外泌体在 mdx 小鼠中的疾病修饰生物活性。
JCI Insight. 2019 Apr 4;4(7). doi: 10.1172/jci.insight.125754.
8
High-Dimensional Single-Cell Cartography Reveals Novel Skeletal Muscle-Resident Cell Populations.高维单细胞图谱揭示新型骨骼肌驻留细胞群体。
Mol Cell. 2019 May 2;74(3):609-621.e6. doi: 10.1016/j.molcel.2019.02.026. Epub 2019 Mar 25.
9
Challenges for mesenchymal stromal cell therapies.间充质基质细胞治疗的挑战。
Sci Transl Med. 2019 Feb 20;11(480). doi: 10.1126/scitranslmed.aat2189.
10
Regenerating the field of cardiovascular cell therapy.心血管细胞治疗领域的再生。
Nat Biotechnol. 2019 Mar;37(3):232-237. doi: 10.1038/s41587-019-0042-1. Epub 2019 Feb 18.
Zotero 插件