Eficacia del trasplante de células madre mesenquimales de lipoaspirado en el tratamiento de lesiones crónicas del manguito rotador. Modelo experimental en ratas / Efficacy of transplantation of lipoaspired mesenchymal stem cells in the treatment of chronic rotator cuff tears. Experimental model in rats

Antecedentes y objetivo: Las roturas del manguito rotador afectan aproximadamente al 30% de la población mayor de 60 años. El tratamiento quirúrgico por vía artroscópica de estas lesiones es el tratamiento de elección, sin embargo, a pesar de las mejoras técnicas de reparación el índice de rerroturas oscila entre el 11 y el 94%. Por ello, los investigadores buscan mejorar el proceso de curación biológica mediante el uso de diferentes alternativas como las células madre mesenquimales (MSC). Nuestro objetivo es evaluar la eficacia de un medicamento de terapia celular elaborado a partir de células madre alogénicas derivadas del tejido adiposo en un modelo de lesión crónica del manguito rotador en ratas. Material y método: Se creó la lesión del supraespinoso en 48 ratas para su posterior sutura a las 4 semanas. A 24 animales se les añadió las MSC en suspensión tras la sutura, y a 24 animales HypoThermosol-FRS® (HTS) como grupo control. En ambos grupos se analizó la histología (escala Åström y Rausing) y la carga máxima, desplazamiento y constante elástica del tendón supraespinoso a los 4 meses de la reparación. Resultados: No se encontraron diferencias estadísticamente significativas en la puntuación histológica comparando los tendones tratados con MSC con respecto a los tendones tratados con HTS (p=0,811) ni tampoco en los resultados de carga máxima (p=0,770), desplazamiento (p=0,852) ni constante elástica (p=0,669) del tendón en ambos grupos. Conclusiones: La adición en suspensión de células derivadas de tejido adiposo a la reparación de una lesión crónica de manguito no mejora las características histológicas ni biomecánicas del tendón suturado.(AU)

Background and aim: Rotator cuff tears emerge in approximately 30% of the population over 60 years of age. Arthroscopic surgical treatment of these lesions is the treatment of choice, however, despite the improved repair techniques, the rate of re-tears ranges between 11 and 94%. Therefore, researchers seek to improve the biological healing process through the use of different alternatives such as mesenchymal stem cells (MSCs). Our objective is to evaluate the efficacy of a Cellular Therapy Drug made from allogeneic stem cells derived from adipose tissue in a rat model of chronic rotator cuff injury. Material and methods: The supraspinatus lesion was created in 48 rats for subsequent suturing at 4 weeks. MSCs in suspension were added to 24 animals after suturing, and HypoThermosol-FRS® (HTS) to 24 animals as a control group. Histology (Åström and Rausing scale) and the maximum load, displacement and elastic constant of the supraspinatus tendon were analyzed in both groups 4 months after the repair. Results: No statistically significant differences were found in the histological score comparing the tendons treated with MSCs with respect to the tendons treated with HTS (P=.811) nor in the results of maximum load (P=.770), displacement (P=.852) or elastic constant (P=.669) of the tendon in both groups. Conclusions: The addition of adipose-derived cells in suspension to the repair of a chronic cuff injury does not improve the histology or biomechanics of the sutured tendon.(AU)

[Translated article] Efficacy of transplantation of lipoaspired mesenchymal stem cells in the treatment of chronic rotator cuff tears. Experimental model in rats / Eficacia del trasplante de células madre mesenquimales de lipoaspirado en el tratamiento de lesiones crónicas del manguito rotador. Modelo experimental en ratas

Antecedentes y objetivo: Las roturas del manguito rotador afectan aproximadamente al 30% de la población mayor de 60 años. El tratamiento quirúrgico por vía artroscópica de estas lesiones es el tratamiento de elección, sin embargo, a pesar de las mejoras técnicas de reparación el índice de rerroturas oscila entre el 11 y el 94%. Por ello, los investigadores buscan mejorar el proceso de curación biológica mediante el uso de diferentes alternativas como las células madre mesenquimales (MSC). Nuestro objetivo es evaluar la eficacia de un medicamento de terapia celular elaborado a partir de células madre alogénicas derivadas del tejido adiposo en un modelo de lesión crónica del manguito rotador en ratas. Material y método: Se creó la lesión del supraespinoso en 48 ratas para su posterior sutura a las 4 semanas. A 24 animales se les añadió las MSC en suspensión tras la sutura, y a 24 animales HypoThermosol-FRS® (HTS) como grupo control. En ambos grupos se analizó la histología (escala Åström y Rausing) y la carga máxima, desplazamiento y constante elástica del tendón supraespinoso a los 4 meses de la reparación. Resultados: No se encontraron diferencias estadísticamente significativas en la puntuación histológica comparando los tendones tratados con MSC con respecto a los tendones tratados con HTS (p=0,811) ni tampoco en los resultados de carga máxima (p=0,770), desplazamiento (p=0,852) ni constante elástica (p=0,669) del tendón en ambos grupos. Conclusiones: La adición en suspensión de células derivadas de tejido adiposo a la reparación de una lesión crónica de manguito no mejora las características histológicas ni biomecánicas del tendón suturado.(AU)

Background and aim: Rotator cuff tears emerge in approximately 30% of the population over 60 years of age. Arthroscopic surgical treatment of these lesions is the treatment of choice, however, despite the improved repair techniques, the rate of re-tears ranges between 11 and 94%. Therefore, researchers seek to improve the biological healing process through the use of different alternatives such as mesenchymal stem cells (MSCs). Our objective is to evaluate the efficacy of a Cellular Therapy Drug made from allogeneic stem cells derived from adipose tissue in a rat model of chronic rotator cuff injury. Material and methods: The supraspinatus lesion was created in 48 rats for subsequent suturing at 4 weeks. MSCs in suspension were added to 24 animals after suturing, and HypoThermosol-FRS® (HTS) to 24 animals as a control group. Histology (Åström and Rausing scale) and the maximum load, displacement and elastic constant of the supraspinatus tendon were analyzed in both groups 4 months after the repair. Results: No statistically significant differences were found in the histological score comparing the tendons treated with MSCs with respect to the tendons treated with HTS (P=.811) nor in the results of maximum load (P=.770), displacement (P=.852) or elastic constant (P=.669) of the tendon in both groups. Conclusions: The addition of adipose-derived cells in suspension to the repair of a chronic cuff injury does not improve the histology or biomechanics of the sutured tendon.(AU)

Tissue Engineering for the Ovine Rotator Cuff: Surgical Anatomy, Approach, Implantation and Histology Technique, along with Review of Literature.

Aim: Tissue engineering is a contemporary topic, which is widely discussed in shoulder surgery. The preclinical success of tissue engineering has not yet fully translated to clinical studies. In this study, we present our experience in this subject and discuss measurements to analyze the sheep tissue as comparative model. We also present a comprehensive systematic review of the literature in relation to tissue engineering and rotator cuff. Method: We studied the anatomy, histology and surgical approach of 24 infraspinatus tendons specimens in sheep and focused on certain measurements such as: (1) size of the normal tendon; (2) diameter of the normal footprint; and (3) bone hardness of the footprint using a durometer. Blood from six sheep was obtained and processed to produce platelet rich plasma using both the Harvest Smartprep and Cascade kit. We then outlined an approach to the infraspinatus tendon footprint in preparation for implantation of a biological augmentation material, which was repaired using a double row technique. This was followed by a histological analysis. Results: The average measurements of the footprint were 21 mm ×21 mm, the tendon length was 35.1 mm and the width proximal and distal was 21.9 and 14 mm, respectively. The average bone hardness at the 12, 3, 6, and 9 o'clock position was 64.1, 52.3, 50.1, and 37.7 respectively. Central footprint and lateral edge hardness was 44.8 and 43.4. Only the Harvest Smartprep and using a modified method, was able to produce a platelet concentration factor of 4. The Cascade method was unable to concentrate sheep blood. Conclusion: The sheep model is a suitable tissue for studying the rotator cuff. The researcher must be aware of certain interspecies caveats. Clinical tissue engineering and surgical techniques must be modified in order to be suitable when using sheep model.

Graft Utilization in the Augmentation of Large-to-Massive Rotator Cuff Repairs: A Systematic Review.

BACKGROUND: Current treatment options for symptomatic large-to-massive rotator cuff tears can reduce pain, but failure rates remain high. Surgeons have incorporated synthetic and biologic grafts to augment these repairs, with promising results. Multiple reviews exist that summarize these products; however, no systematic review has investigated the grafts' ability to maintain structural integrity after augmentation of large-to-massive rotator cuff repairs. PURPOSE: To systematically review and evaluate the effectiveness of grafts in the augmentation of large-to-massive rotator cuff repairs. STUDY DESIGN: Systematic review. METHODS: A comprehensive search of 4 reputable databases was completed. Inclusion criteria were (1) large-to-massive rotator cuff tear, (2) graft augmentation of primary repairs ± primary repair control group, and (3) minimum clinical and radiologic follow-up of 12 months. Two reviewers screened the titles, abstracts, and full articles and extracted the data from eligible studies. Results were summarized into evidence tables stratified by graft origin and level of evidence. RESULTS: Ten studies fit the inclusion criteria. Allograft augmentation was functionally and structurally superior to primary repair controls, with intact repairs in 85% versus 40% of patients (P < .01). This was supported by observational study data. Xenograft augmentation failed to demonstrate superiority to primary repair controls, with worse structural healing rates (27% vs 60%; P =.11). Both comparative studies supported this finding. There have also been many reports of inflammatory reactions with xenograft use. Polypropylene patches are associated with improved structural (83% vs 59% and 49%; P < .01) and functional outcomes when compared with controls and xenograft augmentation; however, randomized data are lacking. CONCLUSION: Augmentation of large-to-massive rotator cuff repairs with human dermal allografts is associated with superior functional and structural outcome when compared with conventional primary repair. Xenograft augmentation failed to demonstrate a statistically significant difference and may be associated with worse rerupture rates and occasional severe inflammatory reactions. Polypropylene patches have initial promising results. Research in this field is limited; future researchers should continue to develop prospective, randomized controlled trials to establish clear recommendations.

Properties of biologic scaffolds and their response to mesenchymal stem cells.

PURPOSE: The purpose of this study was to examine, in vitro, the cellular response of human mesenchymal stem cells (MSCs) to sample types of commercially available scaffolds in comparison with control, native tendon tissue (fresh-frozen rotator cuff tendon allograft). METHODS: MSCs were defined by (1) colony-forming potential; (2) ability to differentiate into tendon, cartilage, bone, and fat tissue; and (3) fluorescence-activated cell sorting analysis (CD73, CD90, CD45). Samples were taken from fresh-frozen human rotator cuff tendon (allograft), human highly cross-linked collagen membrane (Arthroflex; LifeNet Health, Virginia Beach, VA), porcine non-cross-linked collagen membrane (Mucograft; Geistlich Pharma, Lucerne, Switzerland), a human platelet-rich fibrin matrix (PRF-M), and a fibrin matrix based on platelet-rich plasma (ViscoGel; Arthrex, Naples, FL). Cells were counted for adhesion (24 hours), thymidine assay for cell proliferation (96 hours), and live/dead stain for viability (168 hours). Histologic analysis was performed after 21 days, and the unloaded scaffolds were scanned with electron microscopy. RESULTS: MSCs were successfully differentiated into all cell lines. A significantly greater number of cells adhered to both the non-cross-linked porcine collagen scaffold and PRF-M. Cell activity (proliferation) was significantly higher in the non-cross-linked porcine collagen scaffold compared with PRF-M and fibrin matrix based on platelet-rich plasma. There were no significant differences found in the results of the live/dead assay. CONCLUSIONS: Significant differences in the response of human MSCs to biologic scaffolds existed. MSC adhesion, proliferation, and scaffold morphology evaluated by histologic analysis and electron microscopy varied throughout the evaluated types of scaffolds. Non-cross-linked porcine collagen scaffolds showed superior results for cell adhesion and proliferation, as well as on histologic evaluation. CLINICAL RELEVANCE: This study enables the clinician and scientist to choose scaffold materials according to their specific interaction with MSCs.

Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm.

As dense connective tissues connecting bone to muscle and bone to bone, respectively, tendon and ligament (T/L) arise from the somitic mesoderm, originating in a recently discovered somitic compartment, the syndetome. Inductive signals from the adjacent sclerotome and myotome upregulate expression of Scleraxis, a key transcription factor for tenogenic and ligamentogenic differentiation. Understanding T/L development is critical to establishing a knowledge base for improving the healing and repair of T/L injuries, a high-burden disease due to the intrinsically poor natural healing response. Current treatment of the three most common tendon injuries-tearing of the rotator cuff of the shoulder, flexor tendon of the hand, and Achilles tendon-include mostly surgical repair and/or conservative approaches, including biophysical modalities such as rehabilitation and cryotherapy. Unfortunately, the fibrovascular scar formed during healing possesses inferior mechanical and biochemical properties, resulting in compromised tissue functionality. Regenerative approaches have sought to augment the injured tissue with cells, scaffolds, bioactive agents, and mechanical stimulation to improve the natural healing response. The key challenges in restoring full T/L function following injury include optimal combination of these biological agents as well as their delivery to the injury site. A greater understanding of the molecular mechanisms involved in T/L development and natural healing, coupled with the capability of producing complex biomaterials to deliver multiple biofactors with high spatiotemporal resolution and specificity, should lead to regenerative procedures that more closely recapitulate T/L morphogenesis, thereby offering future patients the prospect of T/L regeneration, as opposed to simple tissue repair.

Latissimus dorsi tendon transfer for massive irreparable rotator cuff tears: a systematic review.

Tendon transfers have been proposed as a possible solution to restore pain-free functions, strength, and range of motion in patients with massive and irreparable cuff tears. The aim of this review is to establish the outcomes of (1) latissimus dorsi tendon transfer (LDT-T) surgery performed as a single procedure or in combination with other muscle-tendon transfer procedures, replacement, or both; (2) LDT-T in primary and revision surgery for massive irreparable rotator cuff tears; (3) the LDT-T procedure in relation to subscapularis and teres minor integrity; (4) the LDT-T procedure in relation to the reattachment position on the humeral head of the transferred tendon; (5) the LDT-T procedure performed as a single or a double incision; (6) arthroscopic, open, or combined approach: and (7) the LDT-T procedure in patients with preoperative osteoarthritis and a nonosteoarthritic condition with the evaluation of osteoarthritis progression. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies of levels of evidence I-IV were included. The LDT-T surgical procedure, outcomes, and complications were evaluated. Twenty-two studies describing 493 shoulders in 487 patients were included in our study. There were no prospective randomized, controlled studies. LDT-T is a promising strategy for the management of massive and irreparable rotator cuff tears, even though no agreement was found on several aspects and options of LDT-T. Randomized prospective control studies are still awaited on this subject.

[Applications of biologic augmentations in rotator cuff repair].

Biologic augmentation could promote rotator cuff tendon healing and improve the mechanical properties as well as reduce postoperative adhesion. Biologic augmentations play a vital role in rotator cuff repair and healing. However, most of the studies were performed on animals and clinical outcomes were short-term follow-up. The therapeutic effects should be assessed in multicenter prospective trials.

The arthritic, cuff-deficient shoulder--when is hemiarthroplasty enough?

This article outlines the role of hemiarthroplasty in the treatment of cuff-tear arthropathy. Rotator cuff tear arthropathy, kinematics, and classification are reviewed.