Establishing a Mouse Model to Evaluate Mesenchymal Stem Cells as a Potential Preoperative Adjuvant in the Management of Massive Rotator Cuff Tears (original) (raw)

Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study

International orthopaedics, 2014

The purpose of this study was to evaluate the efficiency of biologic augmentation of rotator cuff repair with iliac crest bone marrow-derived mesenchymal stem cells (MSCs). The prevalence of healing and prevention of re-tears were correlated with the number of MSCs received at the tendon-to-bone interface. Forty-five patients in the study group received concentrated bone marrow-derived MSCs as an adjunct to single-row rotator cuff repair at the time of arthroscopy. The average number of MSCs returned to the patient was 51,000 ± 25,000. Outcomes of patients receiving MSCs during their repair were compared to those of a matched control group of 45 patients who did not receive MSCs. All patients underwent imaging studies of the shoulder with iterative ultrasound performed every month from the first postoperative month to the 24th month. The rotator cuff healing or re-tear was confirmed with MRI postoperatively at three and six months, one and two years and at the most recent follow up ...

Reduced levels of mesenchymal stem cells at the tendon–bone interface tuberosity in patients with symptomatic rotator cuff tear

International Orthopaedics, 2015

Purpose While the use of bone marrow concentrate (BMC) has been described in the treatment of rotator cuff tears, the impact of a rotator cuff injury on the mesenchymal stem cells (MSCs) content present in the human shoulder has not been determined, especially with regard to changes in the levels of MSCs at the tendon-bone interface. With the hypothesis that there was a decreased level of MSCs at the tendon-bone interface tuberosity in patients with rotator cuff tear, we assessed the level of MSCs in the tuberosity of the shoulder of patients undergoing a rotator cuff repair. Methods We analysed the data of 125 patients with symptomatic rotator cuff tears and of 75 control patients without rotator cuff injury. We recorded the following data: size of tear, number of torn tendons, aetiology of the tear, lag time between onset of shoulder symptoms/injury and repair, and also fatty infiltration of muscles. Mesenchymal stem cell content at the tendon-bone interface tuberosity was evaluated by bone marrow aspiration collected in the humeral tuberosities of patients at the beginning of surgery. Results A significant reduction in MSC content (from moderate, 30-50 %, to severe >70 %) at the tendon-bone interface tuberosity relative to the MSC content of the control was observed in all rotator cuff repair study patients. Severity of the decrease was statistically correlated to a number of factors, including the delay between onset of symptoms and surgery, number of involved tendons, fatty infiltration stage and increasing patient age. Conclusion This study demonstrates that the level of MSCs present in the greater tuberosity of patients with a rotator cuff tear decreases as a function of a number of clinical factors, including lag time from tear onset to treatment, tear size, number of tears and stage of fatty infiltration, among others. This information may help the practices in using biologic augmentation of a rotator cuff repair.

Bone Marrow-Derived Mesenchymal Stem Cells Transduced With Scleraxis Improve Rotator Cuff Healing in a Rat Model

The American Journal of Sports Medicine, 2011

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.

Regenerative Medicine in Rotator Cuff Injuries

BioMed Research International, 2014

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. Platelet-rich plasma (PRP) is a whole blood fraction which contains several growth factors. Controlled clinical studies using different autologous PRP formulations have provided controversial results. However, favourable structural healing rates have been observed for surgical repair of small and medium rotator cuff tears. Cell-based approaches have also been suggested to enhance tendon healing. Bone marrow is a well known source of mesenchymal stem cells (MSCs). Recently, ex vivo human studies have isolated and cultured distinct populations of MSCs from rotator cuff tendons, long head of the biceps tendon, subacromial bursa, and glenohumeral synovia. Stem cells therapies represent a novel frontier in the management of rotator cuff disease that required further basic and clinical research.

Stem Cell Therapy for Rotator Cuff Injuries

Journal of Regenerative Medicine & Biology Research, 2023

Rotator cuff injuries are a common issue among athletes and the aging population that have significant impacts on athlete's performance and individuals' quality of life. Traditional treatment options for rotator cuff injuries include physical therapy, surgery, medication and rest. Unfortunately, these traditional treatments options provide limited success in tissue regeneration and restoring function in the injured rotator cuff. Stem cell therapy has emerged as a potential treatment for rotator cuff injuries, offering the promise of enhanced healing and functional recovery. This literature review aims to synthesize the current state of research on stem cell therapy for rotator cuff injuries. The review encompasses a range of studies, including clinical trials and animal case studies. The potential of Mesenchymal Stem Cells (MSCs) derived from adipose tissue and other sources to promote tendon repair and mitigate muscle atrophy and fatty infiltration is a central focus. Studies have explored various approaches, such as intratendinous injection of bone marrow derived MSCs, adipose-derived stem cells loaded with fibrin gel and bone marrow stimulation. Overall, this literature review provides a comprehensive overview of the current landscape of stem cell therapy for rotator cuff injuries, highlighting both the progress made and the areas that require further exploration, as well as the ethical and safety concerns.

Immunomodulation of Pluripotent Stem Cell-Derived Mesenchymal Stem Cells in Rotator Cuff Tears Model

Biomedicines

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). In addition, using a rat model of RCT, the muscle recovery ability of M-MSCs and adult-MSCs was evaluated by conducting a histological analysis and monitoring the cytokine expression level. Results: Using NGS, it was confirmed that M-MSC was suitable for transplantation because of its excellent ability to regulate inflammation that promotes tissue repair and reduced apoptosis and rejection during transplantation. In addition, while M-MSCs persisted for up to 8 weeks in vivo, they significantly reduced in...

Human Rotator Cuff Tears Have an Endogenous, Inducible Stem Cell Source Capable of Improving Muscle Quality and Function After Rotator Cuff Repair

The American Journal of Sports Medicine, 2020

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. Study Design: Controlled laboratory study. Methods: A total of 20 patients between the ages of 40 and 75 years with partial- or full-thickness RC tears of the supraspinatus and evidence of atrophy and FI Goutallier grade 1, 2, or 3 were selected from 2 surgeons at an orthopaedic center. During the surgical repair procedure, supraspinatus muscle biopsy specimens were obtained for analysis as were deltoid muscle biopsy specimens to serve as the control. FAPs and satellite cells were quantified using fluorescence-act...

Effect of Platelet-Rich Plasma and Mesenchymal Stem Cells as Two Biological Alternatives in Rotator Cuff Injury Treatment: A Mini-Review

Research in Molecular Medicine, 2019

The rotator cuff injury introduces as significant damage of trauma and others factors, and currently recognized as a prevalent orthopedic problem. Thus, many clinical procedures have been demonstrated to reduce the complication of rotator cuff injury with varying degrees of success. Platelet-Rich Plasma (PRP) is being enchantingly agreed as one of the most effectiveness strategies for the symptomatic treatment of rotator cuff injury. Many confusing parameters can influence the result of PRP including size of rotator cuff injury, patient age, PRP producing strategy, and number and timing of PRP injections. However, there is some evidences which support beneficial effect PRP in term relieving pain and restoring function, along with minimal adverse effect, in compared with corticosteroids, and other nonsurgical methods. Besides platelet-rich plasma, Mesenchymal Stem Cells (MSCs) are another biological alternative that can be used to treat rotator cuff injuries. Due to lack of large clinical trials applicability, these biological cells have challenges fairly similar to PRP. In conclusion, there is a need for further research to understand the potential application of both of these alternatives as a safe and effective therapeutic option for rotator cuff injuries.