Julius Wolff Institute, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
J Cachexia Sarcopenia Muscle. 2019 Jun;10(3):501-516. doi: 10.1002/jcsm.12416. Epub 2019 Mar 6.
Diseases that jeopardize the musculoskeletal system and cause chronic impairment are prevalent throughout the Western world. In Germany alone, ~1.8 million patients suffer from these diseases annually, and medical expenses have been reported to reach 34.2bn Euros. Although musculoskeletal disorders are seldom fatal, they compromise quality of life and diminish functional capacity. For example, musculoskeletal disorders incur an annual loss of over 0.8 million workforce years to the German economy. Among these diseases, traumatic skeletal muscle injuries are especially problematic because they can occur owing to a variety of causes and are very challenging to treat. In contrast to chronic muscle diseases such as dystrophy, sarcopenia, or cachexia, traumatic muscle injuries inflict damage to localized muscle groups. Although minor muscle trauma heals without severe consequences, no reliable clinical strategy exists to prevent excessive fibrosis or fatty degeneration, both of which occur after severe traumatic injury and contribute to muscle degeneration and dysfunction. Of the many proposed strategies, cell-based approaches have shown the most promising results in numerous pre-clinical studies and have demonstrated success in the handful of clinical trials performed so far. A number of myogenic and non-myogenic cell types benefit muscle healing, either by directly participating in new tissue formation or by stimulating the endogenous processes of muscle repair. These cell types operate via distinct modes of action, and they demonstrate varying levels of feasibility for muscle regeneration depending, to an extent, on the muscle injury model used. While in some models the injury naturally resolves over time, other models have been developed to recapitulate the peculiarities of real-life injuries and therefore mimic the structural and functional impairment observed in humans. Existing limitations of cell therapy approaches include issues related to autologous harvesting, expansion and sorting protocols, optimal dosage, and viability after transplantation. Several clinical trials have been performed to treat skeletal muscle injuries using myogenic progenitor cells or multipotent stromal cells, with promising outcomes. Recent improvements in our understanding of cell behaviour and the mechanistic basis for their modes of action have led to a new paradigm in cell therapies where physical, chemical, and signalling cues presented through biomaterials can instruct cells and enhance their regenerative capacity. Altogether, these studies and experiences provide a positive outlook on future opportunities towards innovative cell-based solutions for treating traumatic muscle injuries-a so far unmet clinical need.
威胁肌肉骨骼系统并导致慢性损伤的疾病在整个西方世界普遍存在。仅在德国，每年就有~180 万患者患有这些疾病，据报道医疗费用已达 342 亿欧元。尽管肌肉骨骼疾病很少致命，但它们会降低生活质量和功能能力。例如，肌肉骨骼疾病每年给德国经济造成超过 0.8 万个劳动力年的损失。在这些疾病中，外伤性骨骼肌损伤尤其成问题，因为它们可能由多种原因引起，而且治疗极具挑战性。与慢性肌肉疾病（如肌营养不良症、肌少症或恶病质）不同，外伤性肌肉损伤会造成局部肌肉群的损伤。尽管轻微的肌肉创伤不会造成严重后果，但目前还没有可靠的临床策略来预防过度纤维化或脂肪变性，这两种情况在严重创伤后都会发生，并导致肌肉退化和功能障碍。在众多提出的策略中，基于细胞的方法在许多临床前研究中显示出最有前途的结果，并在迄今为止进行的少数临床试验中取得了成功。许多肌源性和非肌源性细胞类型都有益于肌肉愈合，要么直接参与新组织的形成，要么通过刺激肌肉修复的内源性过程。这些细胞类型通过不同的作用模式发挥作用，并且它们在一定程度上取决于所使用的肌肉损伤模型，对肌肉再生的可行性程度不同。虽然在某些模型中，损伤会随着时间的推移自然消退，但其他模型已被开发出来以重现现实生活中损伤的特点，从而模拟在人类中观察到的结构和功能损伤。细胞治疗方法的现有局限性包括与自体采集、扩增和分选方案、最佳剂量以及移植后的活力相关的问题。已经进行了几项临床试验，使用肌源性祖细胞或多能基质细胞治疗骨骼肌损伤，取得了有希望的结果。最近，我们对细胞行为的理解以及其作用模式的机制基础的改进，导致了细胞治疗的一个新范例，其中通过生物材料呈现的物理、化学和信号线索可以指导细胞并增强其再生能力。总的来说，这些研究和经验为治疗外伤性肌肉损伤的创新基于细胞的解决方案提供了积极的前景——这是一个迄今为止尚未满足的临床需求。
