Ji Sun Shin

Intra‐Articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritis of the Knee: A Proof‐of‐Concept Clinical Trial

Mesenchymal stem cells (MSCs) are known to have a potential for articular cartilage regeneration. However, most studies focused on focal cartilage defect through surgical implantation. For the treatment of generalized cartilage loss in osteoarthritis, an alternative delivery strategy would be more appropriate. The purpose of this study was to assess the safety and efficacy of intra‐articular injection of autologous adipose tissue derived MSCs (AD‐MSCs) for knee osteoarthritis. We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee. The phase I study consists of three dose‐escalation cohorts; the low‐dose (1.0 × 107 cells), mid‐dose (5.0 × 107), and high‐dose (1.0 × 108) group with three patients each. The phase II included nine patients receiving the high‐dose. The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) at 6 months. Secondary outcomes included clinical, radiological, arthroscopic, and histological evaluations. There was no treatment‐related adverse event. The WOMAC score improved at 6 months after injection in the high‐dose group. The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high‐dose group. Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high‐dose group. Histology demonstrated thick, hyaline‐like cartilage regeneration. These results showed that intra‐articular injection of 1.0 × 108 AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events, and reduced cartilage defects by regeneration of hyaline‐like articular cartilage. Stem Cells 2014;32:1254–1266

Platelet-Rich Plasma for Arthroscopic Repair of Large to Massive Rotator Cuff Tears: A Randomized, Single-Blind, Parallel-Group Trial

Background: Platelet-rich plasma (PRP) is expected to have a biological augmentation potential in the healing of various diseases and injuries, including rotator cuff tears. However, few evaluations have been performed specifically for large to massive tears. Purpose: To assess the efficacy of PRP augmentation in patients undergoing arthroscopic repair for large to massive rotator cuff tears. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 48 patients scheduled for arthroscopic repair of large to massive rotator cuff tears were randomly assigned to receive either PRP-augmented (PRP group) or conventional treatment (conventional group). In the PRP group, 3 PRP gels (3 × 3 mL) were applied to each patient between the torn end and the greater tuberosity. The primary outcome measure was the retear rate assessed by magnetic resonance imaging (MRI) or computed tomographic arthrography (CTA) at a minimum of 9 months after surgery. Secondary outcome measures included pain, range of motion, muscle strength, overall satisfaction, functional scores, and the change in cross-sectional area (CSA) of the supraspinatus. Results: The retear rate of the PRP group (20.0%) was significantly lower than that of the conventional group (55.6%) (P = .023). Clinical outcomes showed no statistical difference between the 2 groups (all P > .05) except for the overall function (P = .043). The change in 1-year postoperative and immediately postoperative CSA was significantly different between the 2 groups: –15.54 ± 94.34 mm2 in the PRP group versus −85.62 ± 103.57 mm2 in the conventional group (P = .047). Conclusion: The application of PRP for large to massive rotator cuff repairs significantly improved structural outcomes, as evidenced by a decreased retear rate and increased CSA of the supraspinatus compared with repairs without PRP augmentation. While there was no significant difference in clinical outcomes except the overall shoulder function after 1-year follow-up, better structural outcomes in the PRP group might suggest improved clinical outcomes at longer term follow-up.

Platelet-Rich Plasma for Arthroscopic Repair of Medium to Large Rotator Cuff Tears: A Randomized Controlled Trial

Background: Two main questions about the use of platelet-rich plasma (PRP) for regeneration purposes are its effect on the speed of healing and the quality of healing. Despite recent numerous studies, evidence is still lacking in this area, especially in a representative patient population with medium to large rotator cuff tears. Purpose: To assess the efficacy of PRP augmentation on the speed and quality of healing in patients undergoing arthroscopic repair for medium to large rotator cuff tears. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 74 patients scheduled for arthroscopic repair of medium to large rotator cuff tears were randomly assigned to undergo either PRP-augmented repair (PRP group) or conventional repair (conventional group). In the PRP group, 3 PRP gels (3 × 3 mL) were applied to each patient between the torn end and the greater tuberosity. The primary outcome was the Constant score at 3 months after surgery. Secondary outcome measures included the visual analog scale (VAS) for pain, range of motion (ROM), muscle strength, overall satisfaction and function, functional scores, retear rate, and change in the cross-sectional area (CSA) of the supraspinatus muscle. Results: There was no difference between the 2 groups in the Constant score at 3 months (P > .05). The 2 groups had similar results on the VAS for pain, ROM, muscle strength, overall satisfaction and function, and other functional scores (all P > .05) except for the VAS for worst pain (P = .043). The retear rate of the PRP group (3.0%) was significantly lower than that of the conventional group (20.0%) (P = .032). The change in 1-year postoperative and immediately postoperative CSAs was significantly different between the 2 groups: –36.76 ± 45.31 mm2 in the PRP group versus −67.47 ± 47.26 mm2 in the conventional group (P = .014). Conclusion: Compared with repairs without PRP augmentation, the current PRP preparation and application methods for medium to large rotator cuff repairs significantly improved the quality, as evidenced by a decreased retear rate and increased CSA of the supraspinatus, but not the speed of healing. However, further studies may be needed to investigate the effects of PRP on the speed of healing without risking the quality.

Changes in Appearance of Fatty Infiltration and Muscle Atrophy of Rotator Cuff Muscles on Magnetic Resonance Imaging After Rotator Cuff Repair: Establishing New Time-Zero Traits

PURPOSE To investigate whether and how arthroscopic rotator cuff repair changes the appearance of fatty infiltration and muscle atrophy as shown on magnetic resonance imaging (MRI) by comparing measurements taken before and immediately after surgery. METHODS The first study determined appropriate measurements of fatty infiltration and muscle atrophy, and the second study assessed immediate postoperative changes caused by surgery per se. Forty-two patients who underwent arthroscopic shoulder surgery for reasons other than rotator cuff repair were included in the first study, and 101 patients who underwent arthroscopic rotator cuff repair were included in the second study. MRI was undertaken preoperatively and 3 days after surgery. Fatty infiltration was evaluated with the Goutallier grade and by measuring signal intensities of rotator cuff muscles, and muscle atrophy was assessed with the tangent sign, occupation ratio, and cross-sectional areas of muscles. RESULTS In the first study, only the cross-sectional area of the subscapularis significantly changed after surgery and was excluded in the second study. In the second study, fatty infiltration seemingly improved by at least 1 grade in 50.0%, 75.0%, and 95.8% of patients with Goutallier grade 2, 3, and 4, respectively, in the supraspinatus (P < .001) and in 28.6%, 57.1%, and 66.7%, respectively, in the infraspinatus (P < .001). Muscle atrophy of the supraspinatus changed by at least 1 grade in 93.6% of patients with a grade 2 tangent sign and 100.0% with a grade 3 tangent sign, as well as 84.0% of patients with a grade 3 occupation ratio; cross-sectional areas of the supraspinatus and infraspinatus significantly increased by 21.6% and 7.0%, respectively (all P < .001). CONCLUSIONS This study showed that arthroscopic rotator cuff repair changed the appearance of both fatty infiltration and muscle atrophy of the supraspinatus and infraspinatus on MRI. We suggest that these changes be considered when one is assessing rotator cuff muscle changes by comparing the appearance on MRI before surgery with that at a certain time after surgery. LEVEL OF EVIDENCE Level IV, therapeutic case series.

Multiple Channeling Improves the Structural Integrity of Rotator Cuff Repair

Background: Multiple channeling is a straightforward additional procedure for rotator cuff repair that creates multiple channels in the greater tuberosity, through which bone marrow of the proximal humerus communicates with the repair site. Purpose: To investigate the effect of multiple channeling on clinical and structural outcomes of arthroscopic rotator cuff repair. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 124 patients with a full-thickness rotator cuff tear were included in the study. Fifty-seven patients underwent arthroscopic rotator cuff repair with multiple channeling (the multiple channeling group) and 67 without it (the conventional group). Analysis of surface markers was performed to characterize the cells recruited by multiple channeling using flow cytometry. Clinical outcomes were evaluated preoperatively and at a minimum of 2 years after surgery (average, 36.79 ± 13.69 months) with respect to pain, range of motion, muscle strength, overall satisfaction, and commonly used functional scores. At a minimum of 9 months after surgery, structural integrity was assessed by magnetic resonance imaging or computed tomography arthrography. Results: Mesenchymal stem cells (MSCs) positive for CD73, CD90, and CD105 and negative for CD45 could be isolated and cultured from bone marrow mononuclear cells of the proximal humerus. Clinical outcomes, including pain, range of motion, strength, overall satisfaction, and functional scores, showed no statistical difference between the 2 groups (all P > .05). The retear rate of the multiple channeling group (22.2%) was significantly lower than that of the conventional group (45.2%) (P = .023). Conclusion: The findings of the study showed that multiple channeling significantly decreased the retear rate after arthroscopic rotator cuff repair, probably via the recruitment of endogenous MSCs from the proximal humerus. Although the results did not show significant differences in the clinical outcomes between the 2 groups, better clinical outcomes might be anticipated in the multiple channeling group via improved structural integrity in a long-term follow-up.

Accuracy of Intra-Articular Injection of the Glenohumeral Joint: A Modified Anterior Approach

PURPOSE This study examined the accuracy of our modified anterior approach to the glenohumeral joint using arthrography. METHODS Two hundred fifty-six consecutive patients with adhesive capsulitis received the glenohumeral joint injection: a mixture of 1 mL of 40 mg of triamcinolone hexacetonide, 2 mL of 2% lidocaine, 3 mL of contrast medium (Ioxitalamate), and 4 mL of normal saline solution, for a total of 10 mL, through a modified anterior approach. Anteroposterior, lateral, and axial arthrography after each injection was performed to determine the accuracy and patterns of the injection. The injection was judged to be successful if some of the contrast medium was placed within the joint. RESULTS There were 78 male and 178 female patients, and the mean age was 54 years (range, 28 to 87 years). In 232 of the 256 patients (90.6%), the injection was deemed to have reached the glenohumeral joint, and these cases were considered successful. Among these patients, the contrast medium was shown only in the joint in 189 (73.8%), whereas in 43 (16.8%) it was shown both in and out of the joint. Of the 24 misguided injections, 15 (5.9%) had anterior placement, 6 (2.3%) had posterior placement, and 2 (0.8%) had superior placement, whereas the material was located in all portions outside the joint in 1 (0.4%). CONCLUSIONS This study showed that our modified anterior approach had an accuracy greater than 90% for the intra-articular injection of the glenohumeral joint without radiographic guidance.

Intra-articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritis of the Knee: A 2-Year Follow-up Study:

Background: The intra-articular injection of mesenchymal stem cells (MSCs) into the knee has shown a potential for the treatment of generalized cartilage loss in osteoarthritis (OA). However, there have been few midterm reports with clinical and structural outcomes. Purpose: To assess the midterm safety and efficacy of an intra-articular injection of autologous adipose tissue–derived (AD) MSCs for knee OA at 2-year follow-up. Study Design: Cohort study; Level of evidence, 3. Methods: Eighteen patients with OA of the knee were enrolled (3 male, 15 female; mean age, 61.8 ± 6.6 years [range, 52-72 years]). Patients in the low-, medium-, and high-dose groups received an intra-articular injection of 1.0 × 107, 5.0 × 107, and 1.0 × 108 AD MSCs into the knee, respectively. Clinical and structural evaluations were performed with widely used methodologies including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and measurements of the size and depth of the cartilage defect, signal intensity of regenerated cartilage, and cartilage volume using magnetic resonance imaging (MRI). Results: There were no treatment-related adverse events during the 2-year period. An intra-articular injection of autologous AD MSCs improved knee function, as measured with the WOMAC, Knee Society clinical rating system (KSS), and Knee injury and Osteoarthritis Outcome Score (KOOS), and reduced knee pain, as measured with the visual analog scale (VAS), for up to 2 years regardless of the cell dosage. However, statistical significance was found mainly in the high-dose group. Clinical outcomes tended to deteriorate after 1 year in the low- and medium-dose groups, whereas those in the high-dose group plateaued until 2 years. The structural outcomes evaluated with MRI also showed similar trends. Conclusion: This study identified the safety and efficacy of an intra-articular injection of AD MSCs into the OA knee over 2 years, encouraging a larger randomized clinical trial. However, this study also showed potential concerns about the durability of clinical and structural outcomes, suggesting the need for further studies. Clinical Trial Registration: NCT01300598

Cross-sectional area of the supraspinatus muscle after rotator cuff repair: an anatomic measure of outcome.

BACKGROUND The change in the cross-sectional area of a repaired muscle, measured with use of magnetic resonance imaging (MRI), could be an indicator of recovery of muscle function. The aims of this study were to evaluate the change in the area of the supraspinatus muscle between the immediately postoperative and one-year postoperative MRIs and to identify factors associated with the change. METHODS Eighty-eight patients with a full-thickness rotator cuff tear were included. MRI was performed three days and one year after surgery. Patients were classified into two groups according to whether the area of the supraspinatus increased or decreased between these two time points. Outcomes including pain, shoulder motion, strength, and commonly used clinical scores were assessed preoperatively and at three, six, and twelve months after surgery. Changes in the rotator cuff muscles and retear of the repaired tendon were also evaluated. RESULTS The area of the supraspinatus muscle increased in twenty-nine (33%) of the patients and decreased in fifty-nine (67%). The change in area was 36.75 ± 27.94 mm² in the group in which it increased and -94.25 ± 70.38 mm² in the group in which it decreased (p < 0.001). Multiple regression analysis indicated that a lower preoperative Simple Shoulder Test (SST) score, better gross visual grade of the tendon at surgery, and greater strength of the supraspinatus at six months postoperatively were associated with an increase in the area. No retear or Sugaya grade of 3 was found in any patient in whom the area increased, whereas 34% of the patients in whom the area decreased had a retear (p < 0.001). CONCLUSIONS This study showed that the cross-sectional area of the supraspinatus muscle could either increase or decrease during the first year after rotator cuff repair and that robust healing (indicated by a Sugaya grade of 1 or 2) and good tendon quality at surgery were important factors associated with an increase in the area. LEVEL OF EVIDENCE Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Allogeneic Platelet-Rich Plasma for Rotator Cuff Repair

ABSTRACT Objective: To investigate the safety and efficacy of allogeneic platelet-rich plasma (PRP) in rotator cuff repair. Methods: Seventeen patients with a full-thickness rotator cuff tear were included. Ten patients underwent arthroscopic rotator cuff repair with allogeneic, and seven patients with autologous PRP. Three PRP gels in a volume 3 ml each were applied between the torn end and the greater tuberosity. Clinical outcomes were assessed preoperatively and at a minimum of 2 years after surgery. Structural outcomes were evaluated with the presence of retear and the change of the cross-sectional area (ACT) of the supraspinatus. Results: Allogeneic PRP did not cause any adverse events during the follow-up period. There was no significant difference in the clinical outcome measures between the two groups (all p > 0.05). The retear rate was 33.3% and 25.0% in the allogeneic group and autologous group, respectively (p = 0.764). The change between the one-year postoperative and immediately postoperative ACT was not also significantly different between the two groups (p = 0.373). Conclusion: Allogeneic PRP in arthroscopic rotator cuff did not cause any local or general complications and that has the efficacy comparable to autologous PRP with respect to the clinical and structural outcomes.Level of Evidence III, Retrospective Comparative Study.