Zhuochang Cai, Longqiang Shu, Chongyang Wang, Xuetao Xie, Xudong Liu
{"title":"M2巨噬细胞衍生的外泌体通过缓解老龄大鼠的细胞衰老促进肌腱到骨的愈合。","authors":"Zhuochang Cai, Longqiang Shu, Chongyang Wang, Xuetao Xie, Xudong Liu","doi":"10.1016/j.arthro.2024.09.021","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To explore the potential of M2 macrophage-derived exosomes (M2-Exos) in enhancing tendon-to-bone healing in aged rats by mitigating cellular senescence of bone marrow-derived stem cells (BMSCs).</p><p><strong>Methods: </strong>In vitro, the effects of M2-Exos on alleviating cellular senescence and improving chondrogenic potential of senescent BMSCs were evaluated. Rats (24 young and 48 aged) with chronic rotator cuff tear (RCT) were repaired and assigned into 3 groups: young group (young rats injected with fibrin at the enthesis), aged group (aged rats injected with fibrin at the enthesis), and aged + M2-Exos group (aged rats injected with fibrin containing M2-Exos at the enthesis). At 6 and 12 weeks after repair, enthesis regeneration was evaluated. Proteomic analysis was conducted to explore the mechanism through which M2-Exos mitigated cellular senescence.</p><p><strong>Results: </strong>In senescent BMSCs treated with M2-Exos, there was a reduction in senescence biomarkers including senescence-associated β-galactosidase, p53, p21, and senescence-associated secretory phenotype (P < .001). M2-Exos also enhanced chondrogenic potential of senescent BMSCs, reflected in greater Bern score (P < .001) and increased expression of Sox9 (P = .013), Col2a1 (P < .001), and Acan (P < .001). Histologically, aged rats treated with M2-Exos demonstrated significantly greater histologic scores (P < .001 at both 6 and 12 weeks) and increased fibrocartilage regeneration at the enthesis. Biomechanically, these rats exhibited greater failure load, stiffness, and stress (all P < .001) at 12 weeks. Mechanistically, proteomic analysis suggested that M2-Exos might alleviate cellular senescence by potentially regulating DNA replication and repair.</p><p><strong>Conclusions: </strong>M2-Exos can significantly alleviate BMSC senescence and thereby enhance tendon-to-bone healing in an aged rat RCT model.</p><p><strong>Clinical relevance: </strong>This study suggests the potential utility of M2-Exos as a therapy for RCT in the older population.</p>","PeriodicalId":55459,"journal":{"name":"Arthroscopy-The Journal of Arthroscopic and Related Surgery","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"M2 Macrophage-Derived Exosomes Promote Tendon-to-Bone Healing by Alleviating Cellular Senescence in Aged Rats.\",\"authors\":\"Zhuochang Cai, Longqiang Shu, Chongyang Wang, Xuetao Xie, Xudong Liu\",\"doi\":\"10.1016/j.arthro.2024.09.021\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To explore the potential of M2 macrophage-derived exosomes (M2-Exos) in enhancing tendon-to-bone healing in aged rats by mitigating cellular senescence of bone marrow-derived stem cells (BMSCs).</p><p><strong>Methods: </strong>In vitro, the effects of M2-Exos on alleviating cellular senescence and improving chondrogenic potential of senescent BMSCs were evaluated. Rats (24 young and 48 aged) with chronic rotator cuff tear (RCT) were repaired and assigned into 3 groups: young group (young rats injected with fibrin at the enthesis), aged group (aged rats injected with fibrin at the enthesis), and aged + M2-Exos group (aged rats injected with fibrin containing M2-Exos at the enthesis). At 6 and 12 weeks after repair, enthesis regeneration was evaluated. Proteomic analysis was conducted to explore the mechanism through which M2-Exos mitigated cellular senescence.</p><p><strong>Results: </strong>In senescent BMSCs treated with M2-Exos, there was a reduction in senescence biomarkers including senescence-associated β-galactosidase, p53, p21, and senescence-associated secretory phenotype (P < .001). M2-Exos also enhanced chondrogenic potential of senescent BMSCs, reflected in greater Bern score (P < .001) and increased expression of Sox9 (P = .013), Col2a1 (P < .001), and Acan (P < .001). Histologically, aged rats treated with M2-Exos demonstrated significantly greater histologic scores (P < .001 at both 6 and 12 weeks) and increased fibrocartilage regeneration at the enthesis. Biomechanically, these rats exhibited greater failure load, stiffness, and stress (all P < .001) at 12 weeks. Mechanistically, proteomic analysis suggested that M2-Exos might alleviate cellular senescence by potentially regulating DNA replication and repair.</p><p><strong>Conclusions: </strong>M2-Exos can significantly alleviate BMSC senescence and thereby enhance tendon-to-bone healing in an aged rat RCT model.</p><p><strong>Clinical relevance: </strong>This study suggests the potential utility of M2-Exos as a therapy for RCT in the older population.</p>\",\"PeriodicalId\":55459,\"journal\":{\"name\":\"Arthroscopy-The Journal of Arthroscopic and Related Surgery\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Arthroscopy-The Journal of Arthroscopic and Related Surgery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.arthro.2024.09.021\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ORTHOPEDICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arthroscopy-The Journal of Arthroscopic and Related Surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.arthro.2024.09.021","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}
M2 Macrophage-Derived Exosomes Promote Tendon-to-Bone Healing by Alleviating Cellular Senescence in Aged Rats.
Purpose: To explore the potential of M2 macrophage-derived exosomes (M2-Exos) in enhancing tendon-to-bone healing in aged rats by mitigating cellular senescence of bone marrow-derived stem cells (BMSCs).
Methods: In vitro, the effects of M2-Exos on alleviating cellular senescence and improving chondrogenic potential of senescent BMSCs were evaluated. Rats (24 young and 48 aged) with chronic rotator cuff tear (RCT) were repaired and assigned into 3 groups: young group (young rats injected with fibrin at the enthesis), aged group (aged rats injected with fibrin at the enthesis), and aged + M2-Exos group (aged rats injected with fibrin containing M2-Exos at the enthesis). At 6 and 12 weeks after repair, enthesis regeneration was evaluated. Proteomic analysis was conducted to explore the mechanism through which M2-Exos mitigated cellular senescence.
Results: In senescent BMSCs treated with M2-Exos, there was a reduction in senescence biomarkers including senescence-associated β-galactosidase, p53, p21, and senescence-associated secretory phenotype (P < .001). M2-Exos also enhanced chondrogenic potential of senescent BMSCs, reflected in greater Bern score (P < .001) and increased expression of Sox9 (P = .013), Col2a1 (P < .001), and Acan (P < .001). Histologically, aged rats treated with M2-Exos demonstrated significantly greater histologic scores (P < .001 at both 6 and 12 weeks) and increased fibrocartilage regeneration at the enthesis. Biomechanically, these rats exhibited greater failure load, stiffness, and stress (all P < .001) at 12 weeks. Mechanistically, proteomic analysis suggested that M2-Exos might alleviate cellular senescence by potentially regulating DNA replication and repair.
Conclusions: M2-Exos can significantly alleviate BMSC senescence and thereby enhance tendon-to-bone healing in an aged rat RCT model.
Clinical relevance: This study suggests the potential utility of M2-Exos as a therapy for RCT in the older population.
期刊介绍：
Nowhere is minimally invasive surgery explained better than in Arthroscopy, the leading peer-reviewed journal in the field. Every issue enables you to put into perspective the usefulness of the various emerging arthroscopic techniques. The advantages and disadvantages of these methods -- along with their applications in various situations -- are discussed in relation to their efficiency, efficacy and cost benefit. As a special incentive, paid subscribers also receive access to the journal expanded website.
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