Stem cell use in rotator cuff tears

BACKGROUND: Rotator cuff Tear (RCT) causes a lot of inconvenience for patients. In most cases, RCT injury does not heal back to bone after repair, and there is a high chance of retearing. Therefore, there is a need to explore more effective targeted therapies. Bone mesenchymal stem cell-derived exosome (BMSCs-Exo) has been proved to be beneficial to the proliferation of tendon cells, but its specific mechanism remains to be further explored. METHODS: BMSCs-Exo was isolated and identified by detecting the specific markers using flow cytometry and western blot assays...

Arthroscopic augmentation of massive and irreparable rotator cuff tears proves to be a valid and evidence-based treatment option to maximize healing and patient outcomes following rotator cuff repair. Integration of acellular dermal allografts as augment or interposition grafts demonstrates definitive benefit in patients with high risk of retear or individuals with severely retracted tears, respectively. Furthermore, these allografts have demonstrated benefit when used for superior capsular repair for chronic, atrophied tears in young, active patients who do not want to proceed with a reverse total shoulder replacement...

Background: In the musculoskeletal system, bone, tendon, and muscle form highly integrated multi-tissue units such as the rotator cuff complex, which facilitates functional and dynamic movement of the shoulder joint. Understanding the intricate interplay among these tissues within clinical, biological, and engineering contexts is vital for addressing challenging issues in treatment of musculoskeletal disorders and injuries. Methods: A wide-ranging literature search was performed, and findings related to the socioeconomic impact of rotator cuff tears, the structure-function relationship of rotator cuff bone-tendon-muscle units, pathophysiology of injury, current clinical treatments, recent state-of-the-art advances (stem cells, growth factors, and exosomes) as well as their regulatory approval, and future strategies aimed at engineering bone-tendon-muscle musculoskeletal units are outlined...

INTRODUCTION: As rotator cuff repairs (RCRs) are among the most common procedures in upper extremity orthopedics, healing augmentation using pharmacologic enhancement of the repaired rotator cuff muscle is of particular interest. OBJECTIVE: The purpose of this study is to review the current understanding of Matrix Metalloproteinases (MMPs), Doxycycline, Testosterone, Estrogen, Growth hormone/ IGF-1, Vitamin D, and Vitamin C as a means to mitigate deleterious effects and propagate factors that support healing following RCR...

Massive rotator cuff tears (MRCTs) of the shoulder cause disability and pain among the adult population. In chronic injuries, the tendon retraction and subsequently the loss of mechanical load lead to muscle atrophy, fat accumulation, and fibrosis formation over time. The intrinsic repair mechanism of muscle and the successful repair of the torn tendon cannot reverse the muscle degeneration following MRCTs. To address these limitations, we developed an electroconductive matrix by incorporating graphene nanoplatelets (GnPs) into aligned poly(l-lactic acid) (PLLA) nanofibers...

BACKGROUND: Rotator cuff tears (RCTs) induce chronic muscle weakness and shoulder pain. Treatment of RCT using surgery or drugs causes lipid infiltration and fibrosis, which hampers tissue regeneration and complete recovery. The pluripotent stem cell-derived multipotent mesenchymal stem cells (M-MSCs) represent potential candidate next-generation therapies for RCT. METHODS: The difference between M-MSCs and adult-MSCs was compared and analyzed using next-generation sequencing (NGS)...

The incidence of re-tearing after rotator cuff repair is very high. The main reason is that the tendon-osseous junction after the operation is scar healed. In response to this problem, research in recent years has focused on the application of grafts, including cell transplantation, periosteum transplantation, cartilage transplantation, and biosynthetic transplantation. Cell transplantation is mainly a variety of stem cells from different sources. The current research has confirmed that it can achieve better results...

Rotator cuff repair remains a challenge clinically due to the high retear rate after surgical intervention. There is a significant need to develop functional biomaterials facilitating tendon-to-bone integration. In this study, hydroxyapatite (HA) incorporated polylactic acid (PLLA) aligned nanofibrous membranes were fabricated by electrospinning as a low-cost sustainable rotator cuff patch. The morphology, physical, mechanical and in vitro cell assays of the nanofibrous membranes were characterized. The results showed that the nanofibrous membrane maintained a rough surface and weakened hydrophobicity...

BACKGROUND: Retraction and degenerative changes of chronic rotator cuff tears limit the healing capacity after routine surgical repair. PURPOSE: To fabricate a mesenchymal stem cell-derived exosome (MSC-Exos) loaded patch and evaluate the effect of this patch on the activity of rabbit tenocytes in vitro and on the repair of chronic rotator cuff tears associated with degenerative changes in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: The MSC-Exos loaded patch was fabricated using a dynamic wet-spinning system...

BACKGROUND: Current nonoperative treatments for partial-thickness rotator cuff tears (PTRCTs) have limited effectiveness in preventing tear progression or promoting tendon healing. This study aimed to establish a rabbit model using in situ-forming fibrin gel containing adipose stem cell-derived exosomes (ASC-Exos/fibrin) to treat PTRCTs. METHODS: Fifty-six rabbits (112 shoulders) were included in this study and assigned to 4 groups: the control group (32 shoulders; PTRCTs without treatment), the fibrin group (32 shoulders; PTRCTs treated with fibrin gel), the ASC-Exo/fibrin group (32 shoulders; PTRCTs treated with ASC-Exos/fibrin), and the sham group (16 shoulders; sham surgery)...

BACKGROUND: Degenerative rotator cuff tendinopathy (RCT) is associated with the senescence of tendon-derived stem cells (TDSCs). Nonsteroidal anti-inflammatory drugs have been demonstrated to alleviate age-associated inflammation (inflamm-aging)-induced cellular senescence of skeletal stem/progenitor cells. However, whether they can alleviate degenerative RCT through reducing inflamm-aging-related TDSC senescence is still unknown. PURPOSE: To assess whether celecoxib can prevent the inflamm-aging-related cellular senescence of TDSCs...

BACKGROUND: Successful management of massive rotator cuff (RC) tendon tears represents a treatment challenge because of the limited intrinsic healing capacity of native tendons and the risk of repair failure. Biologic augmentation of massive RC tears utilizing scaffolds-capable of regenerating bulk tendon tissue to achieve a mechanically functional repair-represents an area of increasing clinical interest. PURPOSE: To investigate the histological and biomechanical outcomes after the use of a novel biologic scaffold fabricated from woven electrochemically aligned collagen (ELAC) threads as a suture-holding, fully load-bearing, defect-bridging scaffold with or without mesenchymal stem cells (MSCs) compared with direct repair in the treatment of critically sized RC defects using a rabbit model...

Rotator cuff tear (RCT) is among the most common shoulder injuries and is prone to rerupture after surgery. Selecting suitable subpopulations of stem cells as a new specific cell type of mesenchymal stem cells has been increasingly used as a potential therapeutic tool in regenerative medicine. In this study, murine adipose-derived SSEA-4+CD90+PDGFRA+ subpopulation cells were successfully sorted, extracted, and identified. These cells showed good proliferation and differentiation potential, especially in the direction of tendon differentiation, as evidenced by qRT-PCR and immunofluorescence...

BACKGROUND: Muscle atrophy, fibrosis, and fatty infiltration are common to a variety of sports-related and degenerative conditions and are thought to be irreversible. Fibroadipogenic progenitors (FAPs) are multipotent resident muscle stem cells with the capacity to differentiate into fibrogenic as well as white and beige adipose tissue (BAT). FAPs that have assumed a BAT differentiation state (FAP-BAT) have proven efficacious in treating muscle degeneration in numerous injury models. PURPOSE: To characterize the subpopulation of murine FAPs with FAP-BAT activity, determine whether their promyogenic effect is mediated via exosomes, and analyze human FAPs for an analogous promyogenic exosome-rich subpopulation...

The purpose of this study is to summarize evidence for the use of adipose stem cell (ASC) injections in the treatment of rotator cuff tears (RCT) and identify future areas of study. A thorough literature search was performed to identify studies investigating the use of ASC injections in the treatment of RCTs. Among animal trials, it is unclear whether ASCs are of benefit for rotator cuff repair. In clinical trials, ASC injection may reduce retear rate with otherwise equivocal clinical outcomes. Although ASC injection may be safe, the literature does not provide a clear consensus as to the efficacy of ASC injections, nor does it delineate which patients would benefit most from this treatment...

Electrospun fibers, with proven ability to promote tissue regeneration, are widely being explored for rotator cuff repairing. However, without post treatment, the microstructure of the electrospun scaffold is vastly different from that of natural extracellular matrix (ECM). Moreover, during mechanical loading, the nanofibers slip that hampers the proliferation and differentiation of migrating stem cells. Here, electrospun nanofiber scaffolds, with crimped nanofibers and welded joints to biomimic the intricate natural microstructure of tendon-to-bone insertion, were prepared using poly(ester-urethane)urea and gelatin via electrospinning and double crosslinking by a multi-bonding network densification strategy...

Background: Tendon-to-bone healing is a difficult process in treatment of rotator cuff tear (RCT). In addition, diabetes is an important risk factor for poor tendon-to-bone healing. Therefore, we investigated the specific mechanisms through which diabetes affects tendon-to-bone healing by regulating the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Methods: Tendon-derived stem cells (TDSCs) were extracted from rats after which their proliferative capacities were evaluated by the MTT assay...

BACKGROUND: Rotator Cuff (RC) tendon tearing is a common clinical problem and there is a high incidence of revision surgery due to re-tearing. In an effort to improve patient outcome and reduce surgical revision, scaffolds have been widely used for augmentation of RC repairs. However, little is known about how scaffolds support tendon stem cell growth or facilitate tendon regeneration. The purpose of this study is to evaluate the structural and biological properties of a bioactive collagen scaffold (BCS) with the potential to promote tendon repair...

ABSTRACT: Postoperative tendon healing is still a matter of concern after rotator cuff repair. Several techniques have been introduced to help improve this healing process. Among them, the bone marrow is commonly used source and a research subject for methods using stem cells to promote wound healing process. A number of studies have shown that bone marrow stem cells can travel up through the holes on the rotator cuff insertion sites, contributing into the rotator cuff repair process, increasing the efficiency of tendon healing and improving clinical results...

BACKGROUND: Fatty infiltration of rotator cuff muscle is a limiting factor in the success of repairs. Fibroadipogenic progenitors (FAPs) are a population of stem cells within the rotator cuff that can differentiate into white adipocytes, fibroblasts, and beige adipocytes. The effects of patient age and rotator cuff tendon tear size on the number, differentiation patterns, and gene expression profiles of FAPs have not yet been analyzed. PURPOSE: To determine if patient age and rotator cuff tear size independently regulate FAP number, differentiation patterns, and gene expression profiles...