Posts by adminjosh
Advances in Stem Cell Therapies for Rotator Cuff Injuries
Rotator cuff injury is a common upper extremity musculoskeletal disease that may lead to persistent pain and functional impairment. Despite the clinical outcomes of the surgical procedures being satisfactory, the repair of the rotator cuff remains problematic, such as through failure of healing, adhesion formation, and fatty infiltration. Stem cells have high proliferation, strong paracrine action, and multiple differentiation potential, which promote tendon remodeling and fibrocartilage formation and increase biomechanical strength. Additionally, stem cell-derived extracellular vesicles (EVs) can increase collagen synthesi and inhibit inflammation and adhesion formation by carrying regulatory proteins and microRNAs. Therefore, stem cell-based therapy is a promising therapeutic strategy that has great potential for rotator cuff healing. In this review, we summarize the advances of stem cells and stem cell-derived EVs in rotator cuff repair and highlight the underlying mechanism of stem cells and stem cell-derived EVs and biomaterial delivery systems. Future studies need to explore stem cell therapy in combination with cellular factors, gene therapy, and novel biomaterial delivery systems.
Stem cell therapies in tendon-bone healing
Abstract
Tendon-bone insertion injuries such as rotator cuff and anterior cruciate ligament injuries are currently highly common and severe. The key method of treating this kind of injury is the reconstruction operation. The success of this reconstructive process depends on the ability of the graft to incorporate into the bone. Recently, there has been substantial discussion about how to enhance the integration of tendon and bone through biological methods. Stem cells like bone marrow mesenchymal stem cells (MSCs), tendon stem/progenitor cells, synovium-derived MSCs, adipose-derived stem cells, or periosteum-derived periosteal stem cells can self-regenerate and potentially differentiate into different cell types, which have been widely used in tissue repair and regeneration. Thus, we concentrate in this review on the current circumstances of tendon-bone healing using stem cell therapy.
Intratendinous Injection of AutologousAdipose Tissue-Derived MesenchymalStem Cells for the Treatment of RotatorCuff Disease: A First-In-Human Trial
ABSTRACT
Despite relatively good results of current symptomatictreatments for rotator cuff disease, there has been an unmetneed for fundamental treatments to halt or reverse the progressof disease. The purpose of this study was to assess the safety andefficacy of intratendinous injection of autologous adiposetissue-derived mesenchymal stem cells (AD MSCs) in patientswith rotator cuff disease. The first part of the study consists ofthree dose-escalation cohorts; the low- (1.0 × 10 cells), mid- (5.0× 10), and high-dose (1.0 × 10) groups with three patients eachfor the evaluation of the safety and tolerability. The second partincluded nine patients receiving the high-dose for theevaluation of the exploratory efficacy. The primary outcomeswere the safety and the shoulder pain and disability index(SPADI). Secondary outcomes included clinical, radiological, andarthroscopic evaluations. Twenty patients were enrolled in thestudy, and two patients were excluded. Intratendinous injectionof AD MSCs was not associated with adverse events. Itsignificantly decreased the SPADI scores by 80% and 77% in themid- and high-dose groups, respectively. Shoulder pain wassignificantly alleviated by 71% in the high-dose group. Magneticresonance imaging examination showed that volume of thebursal-side defect significantly decreased by 90% in the high-dose group. Arthroscopic examination demonstrated thatvolume of the articular- and bursal-side defects decreased by83% and 90% in the mid- and high-dose groups, respectively.Intratendinous injection of autologous AD MSCs in patient witha partial-thickness rotator cuff tear did not cause adverse events,but improved shoulder function, and relieved pain throughregeneration of rotator cuff tendon.
Mesenchymal Stem Cells From a Hypoxic Culture Can Improve Rotator Cuff Tear Repair
Abstract
A rotator cuff tear is an age-related common cause of pain and disability. Studies including our previously published ones have demonstrated that mesenchymal stem cells cultured under hypoxic conditions [hypoxic multipotent stromal cells (MSCs)] facilitate the retention of transplanted cells and promote wound healing. However, there are very few, if any, reports targeting the punctured supraspinatus tendons to create more or equally serous wounds as age-related tears of rotator cuff. It remains to be determined whether transplantation of bone-marrow-derived hypoxic MSCs into the punctured supraspinatus tendon improves tendon repair and, when combined with ultrasound-guided delivery, could be used for future clinical applications. In this study, we used a total of 33 Sprague-Dawley rats in different groups for normal no-punched control, hypoxic MSC treatment, nontreated vehicle control, and MSC preparation, and then evaluated treatment outcomes by biomechanical testing and histological analysis. We found that the ultimate failure load of the hypoxic MSC-treated group was close to that of the normal tendon and significantly greater than that of the nontreated vehicle control group. In vivo tracking of cells labeled with superparamagnetic iron oxide (SPIO) nanoparticles revealed an enhanced retention of transplanted cells at the tear site. Our study demonstrates that hypoxic MSCs improve rotator cuff tear repair in a rat model.