human stem cell use in rotator cuff tear

BACKGROUND: Muscle fatty degeneration following rotator cuff tears has been unequivocally associated with poorer functional outcomes and increased risk for re-tear following rotator cuff repair. Promising results have emerged from animal studies, with the implementation of various interventions for biologic inhibition of this fatty muscle degeneration. The lack of high quality randomized human evidence on this topic, increases the impact of pooled results from animal literature. The aim of the present study was to systematically review the available published literature for animal studies evaluating the ability of several interventions used to mitigate muscle fatty degeneration following the repair of massive rotator cuff tears...

Outcomes after repair of chronic rotator cuff injuries remain suboptimal. Type-1 collagen-rich tendon hydrogel was previously reported to improve healing in a rat chronic rotator cuff injury model. Stem cell seeding of the tendon hydrogel improved bone quality in the same model. This study aimed to examine whether there was a synergistic and dose-dependent effect of platelet-rich plasma (PRP) on tendon-bone interface healing by combining PRP with stem cell-seeded tendon hydrogel. Human cadaveric tendons were processed into a hydrogel...

BACKGROUND: Poor tendon-to-bone healing in chronic rotator cuff tears (RCTs) is related to unsatisfactory outcomes. Exosomes derived from mesenchymal stem cells reportedly enhance rotator cuff healing. However, the difficulty in producing exosomes with a stronger effect on enthesis regeneration must be resolved. PURPOSE: To study the effect of exosomes derived from kartogenin (KGN)-preconditioned human bone marrow mesenchymal stem cells (KGN-Exos) on tendon-to-bone healing in a rat model of chronic RCT...

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...

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...

BACKGROUND: Current clinical treatment options for symptomatic, partial-thickness rotator cuff tear (sPTRCT) offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs)...

BACKGROUND: Adipose stem cell-derived exosomes (ASC-Exos) are reported to effectively prevent muscle atrophy and degeneration of torn rat rotator cuff, but their influence on human samples and their potential mechanism are still unclear. PURPOSE: We aimed to investigate the effects of ASC-Exos on the metabolic activities of torn human rotator cuff tendons and explore the potential mechanism behind it. STUDY DESIGN: Controlled laboratory study...

Rotator cuff repair is a common surgery in sports medicine. During the surgery, torn tendon was re-fixed onto the bony surface. The majority of patients gain good results. However, re-tear occurs in some patients. The reason under this phenomenon is that the normal tendon-bone enthesis cannot be reconstructed. In order to strengthen the tendon-bone healing and promote enthesis regeneration, numerous manners are tested, among which stem cell related therapies are preferred. Stem cells, due to the ability of multi-lineage differentiation, are widely used in regenerative medicine...

Large and massive rotator cuff tears have the highest risk of retear. Common biologic modalities that can potentially reduce the retear rate and improve healing include platelet-rich plasma (PRP), scaffolds, and mesenchymal stem cells (MSCs). PRP has been studied for its role in improving rotator cuff healing and results of randomized controlled trials and meta-analyses show mixed results. Most studies in large and massivge tears show that PRP decreases the retear rate, but the connection between structural integrity and clinical outcomes is still unknown...

BACKGROUND: The muscle quality of the rotator cuff (RC), measured by atrophy and fatty infiltration (FI), is a key determinant of outcomes in RC injury and repair. The ability to regenerate muscle after repair has been shown to be limited. PURPOSE: To determine if there is a source of resident endogenous stem cells, fibroadipogenic progenitor cells (FAPs), within RC injury patients, and if these cells are capable of adipogenic, fibrogenic, and pro-myogenic differentiation...

Regeneration of the gradient structure of the tendon-to-bone interface (TBI) is a crucial goal after rotator cuff repair. The purpose of this study was to investigate the efficacy of a biomimetic hydroxyapatite-gradient scaffold (HA-G scaffold) isolated from adipose tissue (AD) with umbilical cord derived mesenchymal stem cells (UC MSCs) on the regeneration of the structure of the TBI by analyzing the histological and biomechanical changes in a rat repair model. As a result, the HA-G scaffold had progressively increased numbers of hydroxyapatite (HA) particles from the tendon to the bone phase...

BACKGROUND: Chronic full-thickness rotator cuff tears (FTRCTs) represent a major clinical concern because they show highly compromised healing capacity. PURPOSE: To evaluate the efficacy of using a 3-dimensional (3D) bioprinted scaffold with human umbilical cord blood (hUCB)-mesenchymal stem cells (MSCs) for regeneration of chronic FTRCTs in a rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 32 rabbits were randomly assigned to 4 treatment groups (n = 8 per group) at 6 weeks after a 5-mm FTRCT was created on the supraspinatus tendon...

Massive tears of the rotator cuff (RC) are associated with chronic muscle degeneration due to fibrosis, fatty infiltration, and muscle atrophy. The microenvironment of diseased muscle often impairs efficient engraftment and regenerative activity of transplanted myogenic precursors. Accumulating myofibroblasts and fat cells disrupt the muscle stem cell niche and myogenic cell signaling and deposit excess disorganized connective tissue. Therefore, restoration of the damaged stromal niche with non-fibro-adipogenic cells is a prerequisite to successful repair of an injured RC...

There is an ongoing debate about whether to resect or preserve the subacromial bursa during surgical treatment of rotator cuff tears. Neer was the first to systematically describe bursitis as a component of subacromial impingement syndrome that may extend to rotator cuff disease, often discussed as a point of controversy with Uhthoff who first identified the bursa as a contributor to rotator cuff healing, both experimentally and clinically. Because the subacromial bursa provides the gliding mechanism of the shoulder and regenerates itself after surgical removal, interest evolved on the role of the bursa in the healing of rotator cuff tears for evolution of regenerative therapies as a support of arthroscopic repair techniques...

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)...

BACKGROUND: The prevalence of rotator cuff tears increases as patients age due to an attenuated biologic healing capacity. As mechanical advancements in rotator cuff arthroscopic repairs begin to slow, researchers have looked toward using mesenchymal stem cells (MSC) to optimize the shoulder's biologic environment as an alternative route for improvement. OBJECTIVES: This article aims to review the levels of evidence in clinical studies using an injection of MSC in the shoulder joint or obtaining MSC from sources in the shoulder joint to determine if they show promise in augmenting rotator cuff repairs (RCR)...

While therapies using mesenchymal stem cells (MSCs) to treat rotator cuff tendon tear (RCTT) have yielded some promising preliminary results, MSCs therapy has not yet completely regenerated full-thickness RCTT (FTRCTT). It has recently been reported that polydeoxyribonucleotide (PDRN) is effective in the treatment of chronic rotator cuff disease. We hypothesized that local injection of human umbilical cord blood-derived (UCB)-MSCs with PDRN would be more effective in regenerating tendon tear than UCB-MSCs alone...

OBJECTIVE: The aim of this study was to investigate regenerative effects of ultrasound- (US-) guided injection with human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) and/or polydeoxyribonucleotide (PDRN) injection in a chronic traumatic full-thickness rotator cuff tendon tear (FTRCTT) in a rabbit model. METHODS: Rabbits ( n = 32) were allocated into 4 groups. After a 5 mm sized FTRCTT just proximal to the insertion site on the subscapularis tendon was created by excision, the wound was immediately covered by a silicone tube to prevent natural healing...

PURPOSE OF REVIEW: The purpose of this review was to establish the foundation of the major biologic adjuvants to rotator cuff repairs and review recent scientific findings. RECENT FINDINGS: Platelet-rich plasma (PRP) overall has no significant impact on functional outcomes and repair integrity, but may be more advantageous in small to medium tears. Further studies should focus on leukocyte-rich versus poor preparations and the use of PRP in patients that are high risk for repair failure...

BACKGROUND: Massive rotator cuff tears (MRCTs) represent a major clinical concern, especially when degeneration and chronicity are involved, which highly compromise healing capacity. PURPOSE: To study the effect of the secretome of mesenchymal stem cells (MSCs) on tendon cells (TCs) followed by the combination of these activated TCs with an electrospun keratin-based scaffold to develop a tissue engineering strategy to improve tendon-bone interface (TBi) healing in a chronic MRCT rat model...