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Stem cell therapy for rotator cuff tear

Sahishnu Patel, Anthony P Gualtieri, Helen H Lu, William N Levine
Rotator cuff tear is a very common shoulder injury that often necessitates surgical intervention for repair. Despite advances in surgical techniques for rotator cuff repair, there is a high incidence of failure after surgery because of poor healing capacity attributed to many factors. The complexity of tendon-to-bone integration inherently presents a challenge for repair because of a large biomechanical mismatch between the tendon and bone and insufficient regeneration of native tissue, leading to the formation of fibrovascular scar tissue...
October 17, 2016: Annals of the New York Academy of Sciences
Joshua A Greenspoon, Samuel G Moulton, Peter J Millett, Maximilian Petri
BACKGROUND: Surgical treatment of rotator cuff tears has consistently demonstrated good clinical and functional outcomes. However, in some cases, the rotator cuff fails to heal. While improvements in rotator cuff constructs and biomechanics have been made, the role of biologics to aid healing is currently being investigated. METHODS: A selective literature search was performed and personal surgical experiences are reported. RESULTS: Biologic augmentation of rotator cuff repairs can for example be performed wtableith platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs)...
2016: Open Orthopaedics Journal
V Havlas, J Kotaška, P Koníček, T Trč, Š Konrádová, Z Kočí, E Syková
PURPOSE OF THE STUDY Rotator cuff tears are one of the most frequent shoulder disorders which are often associated with pain and interfere with proper arm function. In order to evaluate the safety and effectiveness of using cultured human autologous mesenchymal stem cells (MSC) applied to the suture site during arthroscopic repair of a rotator cuff tear, a prospective clinical study was designed and started recently at the authors' department. Its primary goal was to evaluate the safety of using cultured human MSCs, the secondary goal then was to study a therapeutic effect of their application...
2015: Acta Chirurgiae Orthopaedicae et Traumatologiae Cechoslovaca
Jonathan P Gumucio, Michael D Flood, Stuart M Roche, Kristoffer B Sugg, Adeyiza O Momoh, Paul E Kosnik, Asheesh Bedi, Christopher L Mendias
PURPOSE: Rotator cuff injuries are associated with atrophy and fat infiltration into the muscle, commonly referred to as "fatty degeneration." As the poor function of chronically torn muscles may limit recovery after surgical repair, there is considerable interest in finding therapies to enhance muscle regeneration. Stromal vascular fraction stem cells (SVFCs) can improve muscle regeneration in other chronic injury states, and our objective was to evaluate the ability of SVFCs to reduce fibrosis and fat accumulation, and enhance muscle fibre specific force production after chronic rotator cuff tear...
April 2016: International Orthopaedics
Andre F Steinert, Manuela Kunz, Patrick Prager, Sascha Göbel, Ludger Klein-Hitpass, Regina Ebert, Ulrich Nöth, Franz Jakob, Frank Gohlke
INTRODUCTION: The bursa subacromialis (BS) provides the gliding mechanism of the shoulder and regenerates itself after surgical removal. Therefore, we explored the presence of mesenchymal stem cells (MSCs) within the human adult BS tissue and characterized the BS cells compared to MSCs from bone marrow (BMSCs) on a molecular level. METHODS: BS cells were isolated by collagenase digest from BS tissues derived from patients with degenerative rotator cuff tears, and BMSCs were recovered by adherent culture from bone-marrow of patients with osteoarthritis of the hip...
2015: Stem Cell Research & Therapy
Gretchen A Meyer, Michael C Gibbons, Eugene Sato, John G Lane, Samuel R Ward, Adam J Engler
UNLABELLED: : Chronic rotator cuff (RC) tears are a common and debilitating injury, characterized by dramatic expansion of adipose tissue, muscle atrophy, and limited functional recovery. The role of adipose expansion in RC pathology is unknown; however, given the identified paracrine/endocrine regulation by other adipose depots, it likely affects tissue function outside its boundaries. Therefore, we characterized the epimuscular (EM) fat depot of the human rotator cuff, defined its response to RC tears, and evaluated its influence on myogenesis in vitro...
July 2015: Stem Cells Translational Medicine
David Ross, Tristan Maerz, Michael Kurdziel, Joel Hein, Shashin Doshi, Asheesh Bedi, Kyle Anderson, Kevin Baker
BACKGROUND: The failure rate of tendon-bone healing after repair of rotator cuff tears remains high. A variety of biologic- and cell-based therapies aimed at improving rotator cuff healing have been investigated, and stem cell-based techniques have become increasingly more common. However, most studies have focused on the implantation of exogenous cells, which introduces higher risk and cost. We aimed to improve rotator cuff healing by inducing endogenous stem cell mobilization with systemic administration of granulocyte-colony stimulating factor (G-CSF)...
May 2015: Clinical Orthopaedics and related Research
Olaf Lorbach, Mike H Baums, Tanja Kostuj, Stephan Pauly, Markus Scheibel, Andrew Carr, Nasim Zargar, Maristella F Saccomanno, Giuseppe Milano
UNLABELLED: High initial fixation strength, mechanical stability and biological healing of the tendon-to-bone interface are the main goals after rotator cuff repair surgery. Advances in the understanding of rotator cuff biology and biomechanics as well as improvements in surgical techniques have led to the development of new strategies that may allow a tendon-to-bone interface healing process, rather than the formation of a fibrovascular scar tissue. Although single-row repair remains the most cost-effective technique to address a rotator cuff tear, some biological intervention has been recently introduced to improve tissue healing and clinical outcome of rotator cuff repair...
February 2015: Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA
J Gumucio, M Flood, J Harning, A Phan, S Roche, E Lynch, A Bedi, C Mendias
OBJECTIVES: Rotator cuff tears are among the most common and debilitating upper extremity injuries. Chronic cuff tears result in atrophy and an infiltration of fat into the muscle, a condition commonly referred to as 'fatty degeneration'. While stem cell therapies hold promise for the treatment of cuff tears, a suitable immunodeficient animal model that could be used to study human or other xenograft-based therapies for the treatment of rotator cuff injuries had not previously been identified...
September 2014: Bone & Joint Research
Pietro Randelli, Filippo Randelli, Vincenza Ragone, Alessandra Menon, Riccardo D'Ambrosi, Davide Cucchi, Paolo Cabitza, Giuseppe Banfi
Rotator cuff injuries are a common source of shoulder pathology and result in an important decrease in quality of patient life. Given the frequency of these injuries, as well as the relatively poor result of surgical intervention, it is not surprising that new and innovative strategies like tissue engineering have become more appealing. Tissue-engineering strategies involve the use of cells and/or bioactive factors to promote tendon regeneration via natural processes. The ability of numerous growth factors to affect tendon healing has been extensively analyzed in vitro and in animal models, showing promising results...
2014: BioMed Research International
David Factor, Barry Dale
PURPOSE/BACKGROUND: Tendinopathies are a broad topic that can be examined from the lab to their impact upon function. Improved understanding will serve to bring this pathology to the forefront of discussion, whether in the clinic or the classroom. The purpose of this current concepts clinical commentary is to explore intrinsic and extrinsic mechanisms of rotator cuff (RC) tendinopathy in order to improve clinical and research understanding. METHODS: Pubmed, Medline, Cinahl, PEDro, and Cochrane databases were searched, limiting results to those published in the English language, between the years of 2005 and 2012...
April 2014: International Journal of Sports Physical Therapy
Leonardo Osti, Matteo Buda, Angelo Del Buono
Fatty degeneration is a degenerative condition of the tendon-muscle unit of rotator cuff muscles, characterized by atrophy of muscle fibers, fibrosis, and fatty accumulation within and around the muscles. Many classification may be useful to stage this pathology, especially on Computed Tomography (CT) and magnetic resonance imaging (Mari) findings. Stem cell-based therapies for repair and regeneration of tendons and muscles may be used to promote healing and to make this condition reversible. Diagnosis and management of this condition is mandatory as in patients undergoing rotator cuff repair, it may influence outcomes, increase the likelihood of re-tearing, and evolve negatively...
October 2013: Muscles, Ligaments and Tendons Journal
Umile Giuseppe Longo, Giacomo Rizzello, Alessandra Berton, Ludovica Maltese, Caterina Fumo, Wasim S Khan, Vincenzo Denaro
Rotator cuff tear causes a high rate of morbidity. After surgical repair, the presence of a scar tissue reduces tendon biomechanical properties. Emerging strategies for enhancing tendon healing are growth factors, cytokines, gene therapy and tissue engineering. However their efficacy has to be proved. Growth factors help the process of tendon healing by aiding cells chemotaxis, differentiation and proliferation. Numerous growth factors, including the bone morphogenetic proteins and platelet-derived growth factor can be found during the early healing process of a rotator cuff repair...
November 2013: Current Stem Cell Research & Therapy
Guillermo Arce, Klaus Bak, Gregory Bain, Emilio Calvo, Benno Ejnisman, Giovanni Di Giacomo, Vicente Gutierrez, Dan Guttmann, Eiji Itoi, W Ben Kibler, Tom Ludvigsen, Augustus Mazzocca, Alberto de Castro Pochini, Felix Savoie, Hiroyuki Sugaya, John Uribe, Francisco Vergara, Jaap Willems, Yon Sik Yoo, John W McNeil, Matthew T Provencher
The goal of this article is to consolidate the International Society of Arthroscopy, Knee Surgery & Orthopaedic Sports Medicine (ISAKOS) Upper Extremity Committee's (UEC's) current knowledge on rotator cuff disease and management, as well as highlight key unresolved issues. The rotator cuff is an anatomically complex structure important for providing glenohumeral function and stability as part of a closed chain system. Current consensus suggests rotator cuff injuries are most accurately diagnosed, at levels similar to diagnosis by magnetic resonance imaging, with a combination of cuff- and impingement-specific clinical tests...
November 2013: Arthroscopy: the Journal of Arthroscopic & related Surgery
Pietro Randelli, Erika Conforti, Marco Piccoli, Vincenza Ragone, Pasquale Creo, Federica Cirillo, Pamela Masuzzo, Cristina Tringali, Paolo Cabitza, Guido Tettamanti, Nicoletta Gagliano, Luigi Anastasia
BACKGROUND: Stem cell therapy is expected to offer new alternatives to the traditional therapies of rotator cuff tendon tears. In particular, resident, tissue-specific, adult stem cells seem to have a higher regenerative potential for the tissue where they reside. HYPOTHESIS: Rotator cuff tendon and long head of the biceps tendon possess a resident stem cell population that, when properly stimulated, may be induced to proliferate, thus being potentially usable for tendon regeneration...
July 2013: American Journal of Sports Medicine
Zafar Ahmad, John Wardale, Roger Brooks, Fran Henson, Ali Noorani, Neil Rushton
PURPOSE: To conduct a systematic review of the current evidence for the effects of stem cells on tendon healing in preclinical studies and human studies. METHODS: A systematic search of the PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, and Embase databases was performed for stem cells and tendons with their associated terminology. Data validity was assessed, and data were collected on the outcomes of trials. RESULTS: A total of 27 preclinical studies and 5 clinical studies met the inclusion criteria...
July 2012: Arthroscopy: the Journal of Arthroscopic & related Surgery
Alan J Nixon, Ashlee E Watts, Lauren V Schnabel
Repair of rotator cuff tears in experimental models has been significantly improved by the use of enhanced biologic approaches, including platelet-rich plasma, bone marrow aspirate, growth factor supplements, and cell- and gene-modified cell therapy. Despite added complexity, cell-based therapies form an important part of enhanced repair, and combinations of carrier vehicles, growth factors, and implanted cells provide the best opportunity for robust repair. Bone marrow-derived mesenchymal stem cells provide a stimulus for repair in flexor tendons, but application in rotator cuff repair has not shown universally positive results...
February 2012: Journal of Shoulder and Elbow Surgery
Asheesh Bedi, Travis Maak, Christopher Walsh, Scott A Rodeo, Dan Grande, David M Dines, Joshua S Dines
The pathogenesis of rotator cuff degeneration remains poorly defined, and the incidence of degenerative tears is increasing in the aging population. Rates of recurrent tear and incomplete tendon-to-bone healing after repair remain significant for large and massive tears. Previous studies have documented a disorganized, fibrous junction at the tendon-to-bone interface after rotator cuff healing that does not recapitulate the organization of the native enthesis. Many biologic factors have been implicated in coordinating tendon-to-bone healing and maintenance of the enthesis after rotator cuff repair, including the expression and activation of transforming growth factor-β, basic fibroblast growth factor, platelet-derived growth factor-β, matrix metalloproteinases, and tissue inhibitors of metalloproteinases...
February 2012: Journal of Shoulder and Elbow Surgery
Lawrence V Gulotta, David Kovacevic, Jonathan D Packer, Xiang Hua Deng, Scott A Rodeo
BACKGROUND: Rotator cuffs heal through a scar tissue interface after repair that makes them prone to failure. Scleraxis (Scx) is a basic helix-loop-helix transcription factor that is thought to direct tendon development during embryogenesis. The purpose of this study was to determine if the application of mesenchymal stem cells (MSCs) transduced with adenoviral-mediated scleraxis (Ad-Scx) could improve regeneration of the tendon-bone insertion site in a rat rotator cuff repair model. HYPOTHESIS: Bone marrow-derived cells transduced with Scx would improve the structure of the healing tendon-bone interface and result in increased tendon attachment strength...
June 2011: American Journal of Sports Medicine
Lawrence V Gulotta, Scott A Rodeo
BACKGROUND: Rotator cuffs heal with an interposed layer of scar tissue that makes repairs prone to failure. Cell-based biologic therapies have the potential to augment this healing process. Scleraxis (Scx) is a transcription factor that is involved in tendon development during embryogenesis, and may help drive stem cells toward tenocyte differentiation in adults. QUESTIONS/HYPOTHESIS: (1) Overexpression of Scx with adenoviral-mediated gene transfer in stem cells will drive pluripotent stem cells toward tenoblastogenic lineages in vitro; (2) the application of these genetically modified cells will result in improved histologic and biomechanical healing of rotator cuff repairs...
October 2011: Clinical Orthopaedics and related Research
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