Exosomes Isolated From Adipose-Derived Stem Cells: A New Cell-Free Approach to Prevent the Muscle Degeneration Associated With Torn Rotator Cuffs

2019 ◽  
Vol 47 (13) ◽  
pp. 3247-3255 ◽  
Author(s):  
Chongyang Wang ◽  
Wei Song ◽  
Bi Chen ◽  
Xudong Liu ◽  
Yaohua He
Keyword(s):  
Stem Cells ◽  
Rotator Cuff ◽  
Fatty Infiltration ◽  
Biomechanical Properties ◽  
Rotator Cuff Tears ◽  
Large Animal Model ◽  
Large Animal ◽  
Adipose Derived Stem Cells ◽  
Muscle Degeneration ◽  
Massive Rotator Cuff Tear

Background: Fatty infiltration, inflammation, and apoptosis are common degenerative changes in patients with chronic rotator cuff tears that can lead to muscle atrophy and can even result in massive irreparable rotator cuff tears. Some data have demonstrated the proregenerative, anti-inflammatory, and anti-apoptotic properties of stem cell–derived exosomes in some orthopaedic disorders, but their effect on torn rotator cuff muscles has never been investigated. Purpose: To study the effect of exosomes isolated from human adipose-derived stem cells (ASCs-Exos) on muscle degeneration, regeneration, and biomechanical properties in a rat model of a massive rotator cuff tear (MRCT). Study Design: Controlled laboratory study. Methods: A bilateral supraspinatus and infraspinatus tenotomy was performed on rats to create an MRCT model. Forty-two rats were randomly assigned to 3 groups: the sham surgery group, the saline group (lesions treated with a saline injection), and the ASCs-Exos group (lesions treated with an ASCs-Exos injection). Wet muscle weight, fatty infiltration, inflammation, vascularization, regeneration, and biomechanical properties were evaluated at 8 and 16 weeks after surgery. Results: The results revealed that the ASCs-Exos treatment could prevent the atrophy, fatty infiltration, inflammation, and vascularization of muscles in the MRCT model ( P < .001). Additionally, the myofiber regeneration and biomechanical properties of ASCs-Exos-treated rotator cuffs were significantly elevated compared with those in the saline-treated group ( P < .001). Conclusion: This study demonstrates that ASCs-Exos can effectively decrease atrophy and degeneration and improve muscle regeneration and biomechanical properties in torn rotator cuff muscles. Clinical Relevance: ASCs-Exos can be used as a new cell-free approach to prevent the muscle degeneration associated with torn rotator cuffs and may be helpful to repair torn rotator cuffs. Nevertheless, further work needs to be done in a large animal model owing to the inherent regenerative potential possessed by rodents.

The effect of adipose-derived stem cells on enthesis healing after repair of acute and chronic massive rotator cuff tears in rats

2019 ◽  
Vol 28 (4) ◽  
pp. 654-664 ◽  
Author(s):  
Benjamin B. Rothrauff ◽  
Catherine A. Smith ◽  
Gerald A. Ferrer ◽  
João V. Novaretti ◽  
Thierry Pauyo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Rotator Cuff ◽  
Rotator Cuff Tears ◽  
Adipose Derived Stem Cells ◽  
Massive Rotator Cuff Tears

Postoperative New-Onset Pseudoparalysis: A Retrospective Analysis of 430 Consecutive Arthroscopic Repairs for Large to Massive Rotator Cuff Tears

2018 ◽  
Vol 46 (7) ◽  
pp. 1701-1710 ◽  
Author(s):  
Hyeon Jang Jeong ◽  
Sung Min Rhee ◽  
Joo Han Oh
Keyword(s):  
Risk Factors ◽  
Rotator Cuff ◽  
Fatty Infiltration ◽  
Rotator Cuff Tears ◽  
Level Of Evidence ◽  
Massive Rotator Cuff Tear ◽  
Supraspinatus Tear ◽  
The Mean ◽  
Mean Time ◽  
New Onset

Background: The authors have sometimes encountered postoperative new-onset pseudoparalysis (PONP) after arthroscopic repair for large to massive rotator cuff tear (ARCR). As there are insufficient data regarding PONP, the authors aimed to determine whether such a condition is characterized by obvious risk factors, as well as to assess the conditions under which it can be reversed. Purpose: To evaluate the predictors of PONP development after ARCR and its reversal and to integrate these predictors into a scoring system that can be applied in clinical practice. Study Design: Case-control study; Level of evidence, 3. Methods: The authors retrospectively analyzed 430 consecutive ARCRs performed between March 2010 and May 2016. Patients were stratified according to the occurrence of PONP. To determine the risk factors of PONP, the authors compared the PONP and control groups (patients who did not experience PONP) in terms of demographic, clinical, and operative characteristics. Results were expressed in terms of odds ratios (ORs). Results: The incidence of PONP was 6.0% (26 of 430). Predictors of PONP included torn subscapularis (OR, 7.875; 95% CI, 1.780-34.956; P = .007), ≥30-mm retraction of the torn supraspinatus (OR, 4.657; 95% CI, 1.537-14.203; P = .007), age ≥65 years (OR, 3.865; 95% CI, 1.465-10.040; P = .006), and preoperative stiffness (OR, 2.954; 95% CI, 1.212-7.159; P = .017). The reversal rate of PONP was 65.4% (17 of 26), and the mean time to PONP reversal was 10 months. The occurrence and reversal of PONP were not related to retear. Fatty infiltration of the supraspinatus lower than Goutallier grade 3 was the sole predictor of reversal (OR, 22.000; 95% CI, 1.857-260.648; P = .014). Conclusion: Although the incidence of PONP after ARCR was low (6.0%), the risk of PONP was higher in patients with a torn subscapularis, larger supraspinatus tear size, older age, and preoperative stiffness. The mean time from PONP onset to reversal was 10 months, and PONP reversal was affected solely by fatty infiltration of the supraspinatus. Therefore, surgeons should consider the risk for PONP and attempt to identify high-risk patients before rotator cuff repair.

scholarly journals The role of adipose derived stem cells in the treatment of rotator cuff tears: from basic science to clinical application

2020 ◽  
Author(s):  
Fabrizio Mocini ◽  
Andrea Stefano Monteleone ◽  
Piero Piazza ◽  
Valentina Cardona ◽  
Valeria Vismara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Rotator Cuff ◽  
Basic Science ◽  
State Of The Art ◽  
Research Field ◽  
Rotator Cuff Tears ◽  
Adipose Derived Stem Cells ◽  
Clinical Literature ◽  
Multipotential Differentiation

Over the last decade, regenerative medicine has become increasingly popular throughout the scientific community. The poor healing capacity at the tendon-bone interface makes the rotator cuff an appealing target for biologic agents. Adipose derived stem cells are mesenchymal cells with the capacity for self-renewal and multipotential differentiation. They have been recently proposed, both in isolation and as adjuvants to existing surgical therapies, for the treatment of rotator cuff tears. Several studies have been carried out in this research field, starting from the biological characteristics of adipose derived stem cells, their preparation and culture, up to the application in the experimental field on animal models and on humans. The purpose of this study was to provide a state of the art about the current basic science and clinical literature for the effectiveness of adipose derived stem cells in the treatment of rotator cuff tears.

scholarly journals Fibro-adipogenesis in Injured Rotator Cuff Muscle

2022 ◽  
Author(s):  
Ajith K. Subhash ◽  
Michael Davies ◽  
Andrew Gatto ◽  
Jacob M. Bogdanov ◽  
Rae Lan ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Fatty Infiltration ◽  
Fatty Degeneration ◽  
Biomechanical Properties ◽  
Suprascapular Nerve ◽  
Nerve Compression ◽  
Rotator Cuff Tears ◽  
Post Injury ◽  
Chronic Injury

Abstract Purpose of Review Fibro-adipogenic progenitors were first characterized in 2010 and later found to contribute significantly to muscle regeneration and mediate degenerative changes in muscle following injury. These progenitors were also found to have an influence on the rotator cuff muscle’s response to chronic injury which is defined by fibrosis accompanied by massive fatty degeneration. The purpose of this review is to highlight progenitor cells, their contribution to fibro-adipogenesis in rotator cuff tissue, and the factors influencing fibro-adipogenesis in this tissue. Recent Findings Fibro-adipogenic progenitors are a key mediator of the fatty infiltration notably prevalent in rotator cuff injury. Relative to other muscle groups, the rotator cuff has relatively high rates of fibro-adipogenesis following massive chronic rotator cuff tears. This may be linked to the pre-injury density of fibro-adipogenic progenitors in muscle tissue affecting post-injury levels of fibro-adipogenesis. In addition, suprascapular nerve injury in rat models of rotator cuff tears has demonstrated worse, histologic, and biomechanical properties and lower healing rates of rotator cuff repairs. However, fatty infiltration in the rotator cuff following suprascapular nerve compression has been shown to be reversible following release of the nerve compression. Summary The fibro-adipogenic response to acute and chronic injury in rotator cuff tissue is determined by a complex array of factors including progenitor cell influence, transcriptional pathways, chronicity of the injury, anatomic location of injury, microenvironmental influences, and the severity of nerve involvement. Elucidating the complex interactions of these factors will provide potential targets for therapeutic intervention in vivo.

Zoledronic Acid Substantially Improves Bone Microarchitecture and Biomechanical Properties After Rotator Cuff Repair in a Rodent Chronic Defect Model

2020 ◽  
Vol 48 (9) ◽  
pp. 2151-2160
Author(s):  
Jakob E. Schanda ◽  
Claudia Keibl ◽  
Patrick Heimel ◽  
Xavier Monforte ◽  
Stefan Tangl ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Rotator Cuff ◽  
Humeral Head ◽  
Bone Microarchitecture ◽  
Intervention Group ◽  
Maximum Load ◽  
Biomechanical Properties ◽  
Rotator Cuff Tears ◽  
Mineral Density ◽  
Load To Failure

Background: Bone mineral density at the humeral head is reduced in patients with chronic rotator cuff tears. Bone loss in the humeral head is associated with repair failure after rotator cuff reconstruction. Bisphosphonates (eg, zoledronic acid) increase bone mineral density. Hypothesis: Zoledronic acid improves bone mineral density of the humeral head and biomechanical properties of the enthesis after reconstruction of chronic rotator cuff tears in rats. Study Design: Controlled laboratory study. Methods: A total of 32 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy with delayed transosseous rotator cuff reconstruction after 3 weeks. All rats were sacrificed 8 weeks after rotator cuff repair. Animals were randomly assigned to 1 of 2 groups. At 1 day after rotator cuff reconstruction, the intervention group was treated with a single subcutaneous dose of zoledronic acid at 100 µg/kg bodyweight, and the control group received 1 mL of subcutaneous saline solution. In 12 animals of each group, micro–computed tomography scans of both shoulders were performed as well as biomechanical testing of the supraspinatus enthesis of both sides. In 4 animals of each group, histological analyses were conducted. Results: In the intervention group, bone volume fraction (bone volume/total volume [BV/TV]) of the operated side was higher at the lateral humeral head ( P = .005) and the medial humeral head ( P = .010) compared with the control group. Trabecular number on the operated side was higher at the lateral humeral head ( P = .004) and the medial humeral head ( P = .001) in the intervention group. Maximum load to failure rates on the operated side were higher in the intervention group ( P < .001). Cortical thickness positively correlated with higher maximum load to failure rates in the intervention group ( r = 0.69; P = .026). Histological assessment revealed increased bone formation in the intervention group. Conclusion: Single-dose therapy of zoledronic acid provided an improvement of bone microarchitecture at the humeral head as well as an increase of maximum load to failure rates after transosseous reconstruction of chronic rotator cuff lesions in rats. Clinical Relevance: Zoledronic acid improves bone microarchitecture as well as biomechanical properties after reconstruction of chronic rotator cuff tears in rodents. These results need to be verified in clinical investigations.

Delamination Does Not Affect Outcomes After Arthroscopic Rotator Cuff Repair as Compared With Nondelaminated Rotator Cuff Tears: A Study of 1043 Consecutive Cases

2019 ◽  
Vol 47 (3) ◽  
pp. 674-681 ◽  
Author(s):  
Jieun Kwon ◽  
Ye Hyun Lee ◽  
Sae Hoon Kim ◽  
Jung Hoon Ko ◽  
Byung Kyu Park ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Rotator Cuff ◽  
Rotator Cuff Repair ◽  
Fatty Infiltration ◽  
Arthroscopic Rotator Cuff Repair ◽  
Rotator Cuff Tears ◽  
Symptom Duration ◽  
Negative Prognostic Factor ◽  
Arthroscopic Rotator Cuff ◽  
Cuff Repair

Background: Limited information is available regarding the characteristics of delaminated rotator cuff tears as compared with nondelaminated tears. Furthermore, there is conflicting information regarding the effects of delamination on the anatomic healing of repaired cuffs. Purpose: To evaluate the characteristics and anatomic outcomes of delaminated rotator cuff tears in comparison with nondelaminated tears to determine whether delamination is a negative prognostic factor affecting rotator cuff repair outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: Between 2010 and 2014, 1043 patients were enrolled in the study to assess the prevalence of delamination. Among them, the findings from 531 patients who underwent magnetic resonance imaging or computed tomographic arthrography at least 1 year after surgery were included to determine whether delamination was a negative prognostic factor affecting the anatomic outcomes of arthroscopic rotator cuff repair. Delamination was assessed intraoperatively and defined by distinguishable edge cleavage tearing or interstitial horizontal gap between the articular and bursal surfaces of the torn tendon. One of 3 repair techniques (modified Mason Allen, single row, or double row) was used according to tear configuration and tendon mobilization. The authors evaluated visual analog scale scores for pain and satisfaction and American Shoulder and Elbow Surgeons scores to quantify clinical outcomes. Results: The incidence of delamination was 42.9% (447 of 1043). As compared with those with nondelaminated tears, patients with delaminated tears were older ( P < .001) and had longer symptom duration ( P = .019), larger tear sizes and retractions ( P < .001 for both), higher grades of fatty infiltration of the rotator cuff muscles (all P < .001), and poorer tendon quality ( P < .001). The overall healing failure rate was 19.0% (101 of 531). In univariate analysis, the rate of healing failure for the repaired cuffs was significantly higher in the delaminated group (delaminated tears, 60 of 238, 25.2%; nondelaminated tears, 41 of 293, 14.0%; P = .001). However, results of subgroup and multivariate analyses showed that the presence of delamination was ultimately not an independent risk factor for the failure of cuff healing. Between the delaminated and nondelaminated groups, there was no significant difference in postoperative functional outcomes. Conclusion: The results suggest that delaminated rotator cuff tears might represent chronic degenerative tears of longer symptom duration, with larger tear sizes and higher grades of fatty infiltration in older patients. It appears that delamination could be a confounding factor, not an independent prognostic factor, affecting rotator cuff healing.

1 GENERATION OF A STABLE TRANSGENIC SWINE MODEL FOR CELL TRACKING AND CHROMOSOME DYNAMIC STUDIES

2016 ◽  
Vol 28 (2) ◽  
pp. 130
Author(s):  
R. Sper ◽  
S. Simpson ◽  
X. Zhang ◽  
B. Collins ◽  
J. Piedrahita
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Animal Model ◽  
Regenerative Medicine ◽  
Cancer Biology ◽  
Large Animal Model ◽  
Large Animal ◽  
Fetal Fibroblasts ◽  
Transgene Transmission

Transgenic pigs are an attractive research model in the field of translational research, regenerative medicine, and stem cell therapy due to their anatomic, genetic, and physiological similarities with humans. The development of a transgenic murine model with a fusion of green fluorescent protein (GFP) to histone 2B protein (H2B, protein of nucleosome core) resulted in an easier and more convenient method for tracking cell migration and engraftment levels after transplantation as well as a way to better understand the complexity of molecular regulation within cell cycle/division, cancer biology, and chromosome dynamics. Up to now the development of a stable transgenic large animal model expressing H2B-GFP has not been described. Our objective was to develop the first transgenic porcine H2B-GFP model via CRISPR-CAS9 mediated recombination and somatic cell nuclear transfer (SCNT). Porcine fetal fibroblasts were cotransfected with CRISPR-CAS9 designed to target the 3′ untranslated region of ACTB locus and a targeting vector containing 1Kb homology arms to ACTB flanking an IRES-H2B-GFP transgene. Four days after transfection GFP cells were fluorescence activated cell sorted. Single cell colonies were generated and analysed by PCR, and heterozygous colonies were used as donor cells for SCNT. The custom designed CRISPR-CAS9 knockin system demonstrated a 2.4% knockin efficiency. From positive cells, 119 SCNT embryos were generated and transferred to a recipient gilt resulting in three positive founder boars (P1 generation). Boars show normal fertility (pregnancies obtained via AI of wild type sows). Generated P1 clones were viable and fertile with a transgene transmission rate of 55.8% (in concordance with Mendel’s law upon chi-square test with P = 0.05). Intranuclear H2B-GFP expression was confirmed via fluorescence microscopy on 8-day in vitro cultured SCNT blastocysts and a variety of tissues (heart, kidney, brain, bladder, skeletal muscle, stomach, skin, and so on) and primary cultured cells (chondrocytes, bone marrow derived, adipocyte derived, neural stem cells, and so on) from P1 cloned boars and F1 42-day fetuses and viable piglets. In addition, chromosome segregation could be easily identified during cell cycle division in in vitro cultured stem cells. Custom designed CRISPR-CAS 9 are able to drive homologous recombination in the ACTB locus in porcine fetal fibroblasts, allowing the generation of the first described viable H2B-GFP porcine model via SCNT. Generated clones and F1 generation expressed H2B-GFP ubiquitously, and transgene transmission rates were with concordance of Mendel’s law. This novel large animal model represents an improved platform for regenerative medicine and chromosome dynamic and cancer biology studies.

Characteristics of human satellite cells from rotator cuff tears with or without fatty infiltration

2018 ◽  
Vol 27 (8) ◽  
pp. 1535
Author(s):  
Masashi Koide ◽  
Yoshihiro Hagiwara ◽  
Akira Ando ◽  
Takuya Sekiguchi ◽  
Kenji Kanazawa ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Satellite Cells ◽  
Fatty Infiltration ◽  
Rotator Cuff Tears
Sign in / Sign up

Export Citation Format

Share Document