Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Am J Sports Med. 2020 Jul;48(9):2277-2286. doi: 10.1177/0363546520926462. Epub 2020 Jun 16.
Clinical use of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) has gained momentum as treatment for muscle injuries. Exosomes, or small cell-derived vesicles, could be helpful if they could deliver the same or better physiological effect without cell transplantation into the muscle.
Local delivery of exosomes derived from PRP (PRP-exos) or MSCs (MSC-exos) to injured muscles hastens recovery of contractile function.
Controlled laboratory study.
In a rat model, platelets were isolated from blood, and MSCs were isolated from bone marrow and expanded in culture; exosomes from both were isolated through ultracentrifugation. The tibialis anterior muscles were injured in vivo using maximal lengthening contractions. Muscles were injected with PRP-exos or MSC-exos (immediately after injury and 5 and 10 days after injury); controls received an equal volume of saline. Histological and biochemical analysis was performed on tissues for all groups.
Injury resulted in a significant loss of maximal isometric torque (66% ± 3%) that gradually recovered over 2 weeks. Both PRP-exos and MSC-exos accelerated recovery, with similar faster recovery of contractile function over the saline-treated group at 5, 10, and 15 days after injury ( < .001). A significant increase in centrally nucleated fibers was seen with both types of exosome groups by day 15 ( < .01). Genes involved in skeletal muscle regeneration were modulated by different exosomes. Muscles treated with PRP-exos had increased expression of gene ( < .05), whereas muscles treated with MSC-exos had reduced expression of ( < .05) at 10 days after muscle injury.
Exosomes derived from PRP or MSCs can facilitate recovery after a muscle strain injury in a small-animal model likely because of factors that can modulate inflammation, fibrosis, and myogenesis.
Given their small size, low immunogenicity, and ease with which they can be obtained, exosomes could represent a novel therapy for many orthopaedic ailments.
富含血小板的血浆(PRP)和间充质干细胞(MSCs)在肌肉损伤治疗中的应用越来越受到关注。外泌体是由细胞分泌的小囊泡,如果它们能够在不进行细胞移植到肌肉的情况下,发挥相同或更好的生理作用,那么它们可能会很有帮助。
局部递送 PRP 来源的外泌体(PRP-exos)或 MSCs 来源的外泌体(MSC-exos)到受损肌肉可以加速收缩功能的恢复。
对照实验室研究。
在大鼠模型中,从血液中分离血小板,从骨髓中分离间充质干细胞并在培养中扩增;通过超速离心从两者中分离出外泌体。通过最大延长收缩在体内损伤胫骨前肌。肌肉注射 PRP-exos 或 MSC-exos(损伤后立即和损伤后 5 天和 10 天);对照组接受等量的生理盐水。对所有组的组织进行组织学和生化分析。
损伤导致最大等长扭矩显著丧失(66%±3%),在 2 周内逐渐恢复。PRP-exos 和 MSC-exos 均加速了恢复,与生理盐水处理组相比,在损伤后 5、10 和 15 天,收缩功能的恢复更快(<0.001)。在第 15 天,两种类型的外泌体组都观察到中心核纤维显著增加(<0.01)。不同的外泌体调节与骨骼肌再生相关的基因。PRP-exos 处理的肌肉中基因的表达增加(<0.05),而 MSC-exos 处理的肌肉中基因的表达减少(<0.05)在肌肉损伤后 10 天。
PRP 或 MSCs 衍生的外泌体可以促进小型动物模型中肌肉拉伤后的恢复,这可能是因为它们可以调节炎症、纤维化和肌生成。
鉴于其体积小、免疫原性低以及易于获得,外泌体可能代表许多骨科疾病的一种新的治疗方法。