En-Rung Chiang

Clinical Outcome and Imaging of Arthroscopic Single-Row and Double-Row Rotator Cuff Repair: A Prospective Randomized Trial

PURPOSE The purpose of this study was to compare the clinical and imaging outcomes of single-row and double-row suture anchor fixation in arthroscopic rotator cuff repair with emphasis on analysis of the effect of various tear size on repair integrity. METHODS Fifty-three patents were randomized to either single-row or double-row rotator cuff repair at the time of surgical intervention. The clinical results were evaluated by applying the UCLA score and the ASES index and assessing muscle strength in abduction and external rotation with a minimum 2-year follow-up. The postoperative rotator cuff integrity was evaluated by magnetic resonance arthrography at 6-month and minimum 2-year follow-up. RESULTS We enrolled 27 patients in the single-row group and 26 patients in the double-row group. Statistically, the UCLA score; the ASES index; and muscle strength were significantly increased in both groups after surgery, but there was no significant difference between the 2 groups. At minimum 2-year follow-up, intact rotator cuffs were found in 17 patients in the single-row group and 20 in the double-row group, based on magnetic resonance arthrography results. Overall, there was no significant difference in postoperative structural integrity between the 2 groups at 6-month and 2-year follow-up. In patients with tear size larger than 3 cm, the muscle strength of the shoulder was significantly better in the double-row group. For the final imaging results, regardless of the tear size, there was no difference between the single-row and double-row groups. CONCLUSIONS Arthroscopic rotator cuff repair with double-row fixation showed better shoulder strength in patients with larger tear size (>3 cm) in comparison with single-row fixation. However, the imaging results showed no significant difference in cuff integrity in both groups in patients with any tear size at 6-month and minimum 2-year follow-up. LEVEL OF EVIDENCE Level II, lesser-quality randomized control trial.

Mesenchymal Stem Cells From a Hypoxic Culture Improve and Engraft Achilles Tendon Repair

Background: Bone marrow–derived mesenchymal stem cells (MSCs) from humans cultured under hypoxic conditions increase bone healing capacity. Hypothesis: Rat MSCs cultured under hypoxic conditions increase the tendon healing potential after transplantation into injured Achilles tendons. Study Design: Controlled laboratory study. Methods: Biomechanical testing, histological analysis, and bromodeoxyuridine (BrdU) labeling/collagen immunohistochemistry were performed to demonstrate that augmentation of an Achilles tendon rupture site with hypoxic MSCs increases healing capacity compared with normoxic MSCs and controls. Fifty Sprague-Dawley rats were used for the experiments, with 2 rats as the source of bone marrow MSCs. The cut Achilles tendons in the rats were equally divided into 3 groups: hypoxic MSC, normoxic MSC, and nontreated (vehicle control). The uncut tendons served as normal uncut controls. Outcome measures included mechanical testing in 24 rats, histological analysis, and BrdU labeling/collagen immunohistochemistry in another 24 rats. Results: The ultimate failure load in the hypoxic MSC group was significantly greater than that in the nontreated or normoxic MSC group at 2 weeks after incision (2.1 N/mm2 vs 1.1 N/mm2 or 1.9 N/mm2, respectively) and at 4 weeks after incision (5.5 N/mm2 vs 1.7 N/mm2 or 2.7 N/mm2, respectively). The ultimate failure load in the hypoxic MSC group at 4 weeks after incision (5.5 N/mm2) was close to but still significantly less than that of the uncut tendon (7.2 N/mm2). Histological analysis as determined by the semiquantitative Bonar histopathological grading scale revealed that the hypoxic MSC group underwent a significant improvement in Achilles tendon healing both at 2 and 4 weeks when compared with the nontreated or normoxic MSC group via statistical analysis. Immunohistochemistry further demonstrated that the hypoxic and normoxic MSC groups had stronger immunostaining for type I and type III collagen than did the nontreated group both at 2 and 4 weeks after incision. Moreover, BrdU labeling of MSCs before injection further determined the incorporation and retention of transplanted cells at the rupture site. Conclusion: Transplantation of hypoxic MSCs may be a better and more readily available treatment than normoxic MSCs for Achilles tendon ruptures. Clinical Relevance: The present study provides evidence that transplantation of hypoxic MSCs may be a promising therapy for the treatment of Achilles tendon ruptures.

Isolation of mesenchymal stem cells from shoulder rotator cuff: a potential source for muscle and tendon repair.

The self-healing potential of each tissue belongs to endogenous stem cells residing in the tissue; however, there are currently no reports mentioned for the isolation of human rotator cuff-derived mesenchymal stem cells (RC-MSCs) since. To isolate RC-MSCs, minced rotator cuff samples were first digested with enzymes and the single cell suspensions were seeded in plastic culture dishes. Twenty-four hours later, nonadherent cells were removed and the adherent cells were further cultured. The RC-MSCs had fibroblast-like morphology and were positive for the putative surface markers of MSCs, such as CD44, CD73, CD90, CD105, and CD166, and negative for the putative markers of hematopoietic cells, such as CD34, CD45, and CD133. Similar to BM-MSCs, RC-MSCs were demonstrated to have the potential to undergo osteogenic, adipogenic, and chondrogenic differentiation. Upon induction in the defined media, RC-MSCs also expressed lineage-specific genes, such as Runx 2 and osteocalcin in osteogenic induction, PPAR-γ and LPL in adipogenic differentiation, and aggrecan and Col2a1 in chondrogenic differentiation. The multipotent feature of RC-MSCs in the myogenic injury model was further strengthened by the increase in myogenic potential both in vitro and in vivo when compared with BM-MSCs. These results demonstrate the successful isolation of MSCs from human rotator cuffs and encourage the application of RC-MSCs in myogenic regeneration.

Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits

Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.

Isolation of mesenchymal stem cells from human ligamentum flavum: implicating etiology of ligamentum flavum hypertrophy.

Study Design. To demonstrate the existence of mesenchymal stem cells (MSCs) in ligamentum flavum (LF) and their pathogenic role in LF hypertrophy. Objective. To isolate and characterize LF-derived MSCs and their response to transforming growth factor-beta 1 (TGF-&bgr;1) and trichostatin A (TSA), a histone deacetylase inhibitor (HDACi). Summary of Background Data. LF is a connective tissue, of which hypertrophic changes induce spinal stenosis. The pathogenic role of TGF-&bgr;1 in spinal stenosis has been implicated. TSA has been shown to suppress TGF-&bgr;1–induced alpha-smooth muscle actin (&agr;-SMA), type I and III collagen synthesis in a variety of cells. MSCs have been isolated from a variety of adult tissues, except LF. Whether MSCs exist in LF and their response to TGF-&bgr;1 and TSA is not clear. Methods. The MSCs from LF were isolated and cultured. Their phenotypic character, linage differentiation potential, and response to TGF-&bgr;1 and TSA were analyzed. Results. LF-derived MSCs have the similar profile of surface markers as bone marrow MSCs. They were demonstrated to have the potential to be differentiated into osteoblasts, adipocytes, and chondrocytes. Administration of TGF-&bgr;1 stimulated cell proliferation, enhanced the gene expression of type I and III collagen, and increased the gene expression and protein level of &agr;-SMA. TSA blocked the fibrogenic effects of TGF-&bgr;1. Conclusion. The current results demonstrated the isolation of MSCs from LF. The cellular response to TGF-&bgr;1 implied that these cells might play an important role in the pathogenesis of LF hypertrophy. TSA, which blocks the effects of TGF-&bgr;1, may be a potent therapeutic choice for inhibiting LF hypertrophy.

Hamstring graft sizes differ between Chinese and Caucasians.

PurposeThe use of hamstring tendon autografts for anterior cruciate ligament (ACL) surgery has become more and more common. The purposes of this study were to determine whether anthropomorphic measurement correlated with tendon sizes in Chinese patient group and whether tendon sizes in Chinese and Caucasian patient groups differed.MethodsFrom 2008 to 2009, 100 patients that received double-bundle ACL reconstruction with autologous hamstring tendons were prospectively enrolled. The original lengths and triple-folded graft diameters of the individual semitendinosus (ST) and gracilis (Gr) tendons were recorded and correlated with the anthropometric data (height, weight, body mass index, gender, thigh length, shank length, leg length and bilateral thigh circumference) of the patients. Later, using height for predictions, the original heights of patients were added to the equations previously used for regression models to compare the tendon lengths in different ethnic groups.ResultsAfter stepwise multiple linear regression analysis, the height and leg lengths showed greatest correlation with the lengths of both tendons. The lengths of both the semitendinosus and gracilis tendons in Caucasian patients were significantly longer than in the Chinese patients.ConclusionsThe results of this study showed that anthropomorphic measurements (height and leg length) correlated with tendon lengths. In addition, Caucasians had significantly longer hamstring tendons than the Chinese patients.Level of evidenceProspective cohort study (prevalence), Level I.

Arthroscopic posteroinferior capsular plication and rotator interval closure after Bankart repair in patients with traumatic anterior glenohumeral instability—A minimum follow-up of 5 years

BACKGROUND Shoulder joint laxity over anteroinferior and posteroinferior labral–capsular structure inpatients with traumatic anterior glenohumeral instability was reported in the previous literature. The purpose of this study was to report our experience in arthroscopic treatment of traumatic anterior–inferior shoulder instability by Bankart lesion stabilisation with rotator interval closure and posteroinferior capsular plication. METHODS From August 2000 to November 2004, 45 patients with traumatic anterior–inferior shoulder instability were retrospectively enrolled. Each shoulder was treated with absorbable suture for rotator interval closure and posteroinferior capsular plication after anteroinferior stabilisation. The assessments were performed using the Rowe score, the University of California at Los Angeles (UCLA) shoulder rating scale, the American Shoulder and Elbow Surgeons (ASES) score) and shoulder range of motion (ROM). RESULTS With the average follow-up time of 77.1 months, all shoulder scores improved after surgery(P < 0.001). The average ROM deficit of the operated shoulders was not significant (P > 0.05) as compared with the healthy side. A total of 42 shoulders remained stable (93.3%) and there were three recurrences (6.6%). All patients without recurrence returned to their pre-injury levels of athletic activity. CONCLUSIONS In patients with anterior glenohumeral instability, arthroscopic stabilisation of anteroinferior capsulolabral structure with rotator interval closure and posteroinferior capsular plication provided a reasonable result without significant loss of ROM at a minimum follow-up of 5 years.

Arthroscopic Treatment for Pigmented Villonodular Synovitis of the Shoulder Associated With Massive Rotator Cuff Tear

PURPOSE Our purpose was to investigate arthroscopic treatment of patients diagnosed with pigmented villonodular synovitis (PVNS) of the shoulder and massive rotator cuff tear with the initial presentation of large, recurrent joint effusion. METHODS From December 2005 to June 2007, 5 patients (3 males and 2 females) diagnosed with PVNS of the shoulder and massive rotator cuff tear were treated with arthroscopic synovectomy, partial cuff repair, or debridement if the cuff was irreparable. All 5 patients were followed-up for a mean of 22.4 months (range, 12 to 33 months). Outcomes were measured with use of the American Shoulder and Elbow Surgeons (ASES) and University of California at Los Angeles (UCLA) scoring systems. Two patients received partial rotator cuff repair by suture anchors and another 2 received suture repairs only. All of the patients had residual tear with variable sizes. RESULTS With a mean follow-up of 22.4 months (range, 12 to 33 months), the mean ASES and UCLA scores improved from preoperative values of 48.2 and 7.8 to 80.0 and 29.6 points, respectively (P < .05). All patients were satisfied with the procedure, and no signs of recurrence were noted during the follow-up period. CONCLUSIONS Five cases of PVNS of the shoulder and massive rotator cuff tears with the initial symptoms of shoulder effusion and function limitation were reported. After arthroscopic synovectomy and partial rotator cuff repair or debridement, all patients gained symptomatic and limited functional improvement at an average follow-up of 22 months. LEVEL OF EVIDENCE Level IV, therapeutic case series.

Trichostatin A inhibits TGF‐β1 induced in vitro chondrogenesis of hMSCs through Sp1 suppression

Trichostatin A (TSA) is a histone deacetylase inhibitor (HDACi) known to modulate differentiation of many cells. However, its effect on chondrogenesis remains elusive. This study was aimed to investigate the effects of TSA on in vitro transforming growth factor-β1 (TGF-β1)-induced chondrogenesis of human mesenchymal stem cells (hMSCs). The pellet cultures of hMSCs in a chondrogenic medium were exposed to TGF-β1 and TSA. Quantitative reverse transcription/polymerase chain reaction (PCR) analysis, Alcian blue staining, and immunohistochemistry staining were used to confirm and compare the differences in chondrogenesis by analyzing the mRNA of chondrogenic genes (Sox9, Aggrecan, and Col2A1), synthesis of chondrogenic proteins and type II collagen, respectively. TGF-β1 signaling and its downstream targets were determined by western blot analysis. TGF-β1 led to significant increases in chondrogenic gene expression and the synthesis of chondrogenic proteins. However, TSA significantly decreased chondrogenic gene expression and the synthesis of chondrogenic proteins in a dose-dependent manner. TGF-β1 increased phosphorylation of Smad 2/3 and Sp1 expression around half an hour after induction. The increase of Sp1, but not Smad 2/3 activation was almost completely blocked by the addition of TSA. The chondrogenic effect of TGF-β1 was also suppressed by the Sp1-binding inhibitor mithramycin A. Finally, overexpression of Sp1 abolished TSA-mediated inhibition of TGF-β1-induced chondrogenesis. Our study showed that TSA inhibited chondrogenesis through inhibition of TGF-β1-induced Sp1 expression. Furthermore, Sp1 could be a useful tool in future studies looking into biological mechanisms by which chondrogenesis of hMSCs can be augmented, especially in the area of clinical application.

Fibromatosis stem cells rather than bone-marrow mesenchymal stem cells recapitulate a murine model of fibromatosis.

Palmar fibromatosis is a benign fibroproliferative tumor of unknown etiology, with a high rate of recurrence after excision. The offending cells of palmar fibromatosis are myofibroblasts and the cellular origin of other myofibroblasts has previously been reported to be the bone marrow. However, further clarification of the relationship between bone marrow precursors and palmar fibromatosis is required. Stem cells (SCs) are known to exist in various tissues, but whether SCs can be isolated from fibromatosis tissue is still unclear. The purpose of this study was to isolate and identify stem cells from human palmar fibromatosis, and to evaluate the differences in the differentiation and fibrogenic capacities of bone marrow stem cells (BMSCs) and fibromatosis-derived stem cells (FSCs). We found that FSCs had better fibrogenic differentiation potential than BMSCs, whereas BMSCs had better adipogenic and chondrogenic differentiation capacities. Treatment with transforming growth factor-β1 increased the expression of α-smooth muscle actin, and types III and I collagen significantly more in FSCs than in BMSCs. An in vivo study further confirmed the results of fibrogenesis and suggested that FSCs can recapitulate the fibromatosis nodule. In summary, their myofibroblastic differentiation both in vivo and in vitro makes FSCs a potential cell source for future applications in murine models of fibromatosis or fibrogenesis.