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Extracellular vesicles from rat-bone-marrow mesenchymal stromal/stem cells improve tendon repair in rat Achilles tendon injury model in dose-dependent manner: A pilot study.

ABSTRACT: Mesenchymal stromal/stem cells (MSCs) are increasingly employed for tissue regeneration, largely mediated through paracrine actions. Currently, extracellular vesicles (EVs) released by MSCs are major mediators of these paracrine effects. We evaluated whether rat-bone-marrow-MSC-derived EVs (rBMSCs-EVs) can ameliorate tendon injury in an in vivo rat model. Pro-collagen1A2 and MMP14 protein are expressed in rBMSC-EVs, and are important factors for extracellular-matrix tendon-remodeling. In addition, we found pro-collagen1A2 in rBMSC-EV surface-membranes by dot blot. In vitro on cells isolated from Achilles tendons, utilized as rBMSC -EVs recipient cells, EVs at both low and high doses induce migration of tenocytes; at higher concentration, they induce proliferation and increase expression of Collagen type I in tenocytes. Pretreatment with trypsin abrogate the effect of EVs on cell proliferation and migration, and the expression of collagen I. When either low- or high-dose rBMSCs-EVs were injected into a rat-Achilles tendon injury-model (immediately after damage), at 30 days, rBMSC-EVs were found to have accelerated the remodeling stage of tendon repair in a dose-dependent manner. At histology and histomorphology evaluation, high doses of rBMSCs-EVs produced better restoration of tendon architecture, with optimal tendon-fiber alignment and lower vascularity. Higher EV-concentrations demonstrated greater expression of collagen type I and lower expression of collagen type III. BMSC-EVs hold promise as a novel cell-free modality for the management of tendon injuries.

SUBMITTER: Gissi C

PROVIDER: S-EPMC7067391 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Extracellular vesicles from rat-bone-marrow mesenchymal stromal/stem cells improve tendon repair in rat Achilles tendon injury model in dose-dependent manner: A pilot study.

Gissi Clarissa C Radeghieri Annalisa A Antonetti Lamorgese Passeri Cristina C Gallorini Marialucia M Calciano Lucia L Oliva Francesco F Veronesi Francesca F Zendrini Andrea A Cataldi Amelia A Bergese Paolo P Maffulli Nicola N Berardi Anna Concetta AC

PloS one 20200312 3

Mesenchymal stromal/stem cells (MSCs) are increasingly employed for tissue regeneration, largely mediated through paracrine actions. Currently, extracellular vesicles (EVs) released by MSCs are major mediators of these paracrine effects. We evaluated whether rat-bone-marrow-MSC-derived EVs (rBMSCs-EVs) can ameliorate tendon injury in an in vivo rat model. Pro-collagen1A2 and MMP14 protein are expressed in rBMSC-EVs, and are important factors for extracellular-matrix tendon-remodeling. In additio ...[more]

PMID: 32163452

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Project description:BACKGROUND:Bone marrow aspirate is a primary source for cell-based therapies with increasing value in the world of orthopaedic surgery, especially in revision cases of tendon and ligament repairs. However, cells within peritendinous structures, such as the paratenon and surrounding bursa, contribute to the native tendon-healing response and offer promising cell populations for cell-based repair strategies. Therefore, the purpose of this study is to investigate the efficacy of cells derived from human subacromial bursa as compared with the current gold standard, bone marrow stromal cells (BMSCs), for tendon repairs in an established in vivo immunodeficient murine patellar tendon defect model. HYPOTHESIS:Subacromial bursal cells will show superior survival and engraftment into the host tissue as compared with BMSCs. STUDY DESIGN:Controlled laboratory study. METHODS:Human subacromial bursal and bone marrow aspirate were harvested from the same donor undergoing rotator cuff repair. Cells were transfected with a fluorescent lentiviral vector to permanently label the cells, encapsulated into fibrin gel, and implanted into bilateral full-length central-width patellar tendon defects of immunodeficient mice. Additional surgery was performed on control mice comparing fibrin without cells and natural healing. At the time of sacrifice, all limbs were scanned on a multiphoton microscope to monitor the engraftment of the human donor cells. Afterward, limbs were assigned to either immunohistochemical or biomechanical analysis. RESULTS:As compared with BMSCs, implanted subacromial bursal cells displayed superior tissue engraftment and survival. The main healing response in this defect model was the creation of new healing tissue over the anterior surface of the defect space. The implantation of cells significantly increased the thickness of the anterior healing tissue as compared with control limbs that did not receive cells. Cell proliferation was also increased in limbs that received implanted cells, suggesting that the donor cells stimulated a more robust healing response. Finally, these changes in the healing response did not lead to significant changes in mechanical properties. CONCLUSION:The subacromial bursa, while often removed during rotator cuff repair, may harbor a more suitable cell source for tendon repair than BMSCs, as bursal cells display superior engraftment and survival in tendon tissue. In addition, the subacromial bursa may be a more accessible cell source than bone marrow aspirate. CLINICAL RELEVANCE:The subacromial bursa contains a cell population that responds to tendon injury and may provide a more optimal cell source for tendon repair and regeneration strategies. Therefore, cells could be harvested from this tissue in the future, as opposed to the current practice of bursectomy and debridement.

Project description:BackgroundNicotine is a modifiable risk factor that is well demonstrated to cause deleterious effects on tendon healing and overall health. Individuals that have a dependence on nicotine may be at an elevated risk for numerous postoperative complications when compared to nondependent patients. The purpose of this study is to evaluate the complications postoperatively between nicotine- and non-nicotine-dependent Achilles tendon repairs.MethodsThe global health network database, TriNetX, was used to access and analyze deidentified patient information. Two cohorts were identified for the purposes of this study. Cohort A was defined as patients who had an Achilles tendon repair (Current Procedural Terminology [CPT]: 27650 or CPT: 27654) and had a dependence to nicotine (International Classification of Diseases, Tenth Revision, code: F17). Cohort B was defined as patients who had an Achilles tendon repair but did not have a dependence to nicotine. Data were gathered from health care organizations from August 21, 2000, to August 21, 2023. All postoperative complications were analyzed between 1 and 90 days after the Achilles tendon repair.ResultsA total of 2117 nicotine-dependent patients were matched with 18 102 non-nicotine-dependent patients. After propensity matching for age at event, ethnicity, race, sex, and type 2 diabetes mellitus, nicotine-dependent patients who underwent Achilles tendon repair experienced higher associated risk for numerous postoperative complications. When compared to nondependent patients, nicotine-dependent patients had increased risk for wound disruption (risk ratio [RR] 1.55, 95% CI 1.11-2.16) and infection following a procedure (RR 1.64, 95% CI 1.09-2.47) within 90 days post Achilles tendon repair.ConclusionIn this database study using propensity matching, nicotine-dependent patients who underwent Achilles tendon repair were correlated with an increased associated risk for wound disruption and infection after a procedure than their non-nicotine-dependent counterpart.Level of evidenceLevel III, retrospective cohort study.

Project description:BackgroundTo reduce incision complications, minimally invasive operative approaches for treatment with acute Achilles tendon rupture have been developed, such as Mini-open repair and percutaneous repair. Which technique is the better surgical option? In the present study, we compared the two surgical procedures- modified Mini-open repair versus percutaneous repair-in the treatment of acute Achilles tendon rupture.MethodsFrom January 2016 to November 2018, 68 matched patients with acute Achilles tendon rupture were divided into treatment group (Mini-open with modified Ma-Griffith technique) and control group (the Ma-Griffith technique). The patients were then treated with different surgical techniques and followed up for no less than 24 months, and the functional outcome scores and complications were retrospectively evaluated.ResultsThe mean follow-up time in Mini-open repair group was 29.0±2.9 months, and that in control group was 27.9±2.9 months (P=0.147). The Mini-open repair group showed reliably higher American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score and Achilles tendon Total Rupture Score (ATRS) than the control group in functional assessment (95.0±3.8 vs. 92.3±5.3, P=0.000; 93.8±3.8 vs. 90.9±4.5,P=0.000). There was no cases of sural nerve injury in Mini-open repair group, whereas the percutaneous repair group had 5 cases of the same (P=0.027). No significant differences were found in the calf circumference (32.3±3.9 vs. 31.8±3.6) (P=0.564), range of motion of the ankle (51.3±4.8 vs. 50.5±4.2, P=0.362), or wound complications (34/0 vs. 34/0) (P=1.000) between the two groups at the end of the follow-up time. However, the percutaneous repair group had a shorter average operating time (23.1±5.2 min) than that of the Mini-open repair group (27.7±4.3 min) (P=0.000).ConclusionsAcute Achilles tendon ruptures may be treated successfully with a new Mini-open repair system or percutaneous repair technique. However, the Mini-open repair system may represent a superior surgical option, since it offers advantages in terms of direct visual control of the repair, AOFAS Ankle-Hindfoot Score, Achilles tendon Total Rupture Score and risk of sural nerve palsy.Study designCase-control studies, Level of evidence, 3.

Dataset Information

Extracellular vesicles from rat-bone-marrow mesenchymal stromal/stem cells improve tendon repair in rat Achilles tendon injury model in dose-dependent manner: A pilot study.

Publications

Extracellular vesicles from rat-bone-marrow mesenchymal stromal/stem cells improve tendon repair in rat Achilles tendon injury model in dose-dependent manner: A pilot study.

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