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富含血小板的血浆和间充质干细胞分离的外泌体促进肌肉损伤后的功能恢复。

Exosomes Isolated From Platelet-Rich Plasma and Mesenchymal Stem Cells Promote Recovery of Function After Muscle Injury.

机构信息

Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

出版信息

Am J Sports Med. 2020 Jul;48(9):2277-2286. doi: 10.1177/0363546520926462. Epub 2020 Jun 16.

Abstract

BACKGROUND

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.

HYPOTHESIS

Local delivery of exosomes derived from PRP (PRP-exos) or MSCs (MSC-exos) to injured muscles hastens recovery of contractile function.

STUDY DESIGN

Controlled laboratory study.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

CLINICAL RELEVANCE

Given their small size, low immunogenicity, and ease with which they can be obtained, exosomes could represent a novel therapy for many orthopaedic ailments.

摘要

背景

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。

假说

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。

研究设计

对照实验室研究。

方法

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。

结果

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。

结论

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。

临床相关性

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。

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