Yong Gon Koh

Mesenchymal Stem Cell Implantation in Osteoarthritic Knees Is Fibrin Glue Effective as a Scaffold

Background: The cell-based tissue engineering approach that uses mesenchymal stem cells (MSCs) has addressed the issue of articular cartilage repair in osteoarthritic (OA) knees. However, to improve outcomes, an advanced surgical procedure with tissue-engineered scaffolds may be needed to treat patients with large cartilage lesions. Purpose: To investigate the clinical and second-look arthroscopic outcomes of the implantation of MSCs loaded in fibrin glue as a scaffold in patients with OA knees and to compare these outcomes with those of MSC implantation without a scaffold. Study Design: Cohort study; Level of evidence, 3. Methods: This study retrospectively evaluated 54 patients (56 knees) who were examined with second-look arthroscopy after MSC implantation for cartilage lesions in their OA knees. Patients were divided into 2 groups: 37 patients (39 knees) were treated with MSC implantation without a scaffold (group 1), and 17 patients (17 knees) underwent implantation of MSCs loaded in fibrin glue as a scaffold (group 2). Clinical outcomes were evaluated according to the International Knee Documentation Committee (IKDC) score and the Tegner activity scale, and cartilage repair was assessed with the International Cartilage Repair Society (ICRS) grade. Statistical analyses were performed to identify various prognostic factors associated with the clinical and second-look arthroscopic outcomes. Results: At final follow-up (mean, 28.6 months; range, 24-34 months), the mean IKDC score and Tegner activity scale in each group significantly improved: group 1, from 38.1 ± 7.7 to 62.0 ± 11.7 (IKDC) and from 2.5 ± 0.9 to 3.5 ± 0.8 (Tegner); group 2, from 36.1 ± 6.2 to 64.4 ± 11.5 (IKDC) and from 2.2 ± 0.8 to 3.8 ± 0.8 (Tegner) (P < .001 for all). According to the overall ICRS cartilage repair grades, 9 of the 39 lesions (23%) in group 1 and 12 of the 17 lesions (58%) in group 2 achieved a grade of I or II. There was a significant difference in ICRS grades between the groups (P = .028). Overweight (body mass index ≥ 27.5 kg/m2) and large lesion size (≥5.7 cm2) were significant predictors of poor clinical and arthroscopic outcomes in group 1 (P < .05 for both). There was a similar trend in group 2, but the differences were not significant, possibly owing to the smaller sample size. Conclusion: Clinical and arthroscopic outcomes of MSC implantation were encouraging for OA knees in both groups, although there were no significant differences in outcome scores between groups. However, at second-look arthroscopy, there were better ICRS grades in group 2.

Second-Look Arthroscopic Evaluation of Cartilage Lesions After Mesenchymal Stem Cell Implantation in Osteoarthritic Knees

Background: Cartilage regenerative procedures have been receiving increased interest because of their potential to alter the progression of osteoarthritis (OA). The application of mesenchymal stem cells (MSCs) has been proposed as a new treatment option for OA based on the ability of these cells to differentiate into chondrocytes. Purpose: To investigate the clinical and second-look arthroscopic outcomes of MSC implantation and to identify prognostic factors associated with this treatment. Study Design: Case series; Level of evidence, 4. Methods: This study retrospectively evaluated 37 knees examined using second-look arthroscopic surgery after MSC implantation for cartilage lesions in OA knees. Clinical outcomes were evaluated according to the International Knee Documentation Committee (IKDC) score and Tegner activity scale, and cartilage repair was assessed using International Cartilage Repair Society (ICRS) grading. Statistical analyses were performed to identify various prognostic factors associated with the clinical and second-look arthroscopic outcomes. Results: The mean patient age was 57.4 years (range, 48-69 years), the mean follow-up period was 26.5 months (range, 24-34 months), the mean body mass index (BMI) was 26.3 kg/m2 (range, 19.8-31.2 kg/m2), and the mean lesion size was 5.4 ± 2.9 cm2 (range, 2.3-8.9 cm2). The mean IKDC and Tegner activity scale scores were significantly improved from 38.0 ± 7.8 to 61.0 ± 11.0 and from 2.5 ± 0.5 to 3.6 ± 0.7, respectively (P < .001 for both). According to the ICRS overall repair grades at second-look arthroscopic surgery, 2 of the 37 lesions (5%) were grade I (normal), 7 (19%) were grade II (near normal), 20 (54%) were grade III (abnormal), and 8 (22%) were grade IV (severely abnormal). In terms of overall patient satisfaction with the operation, 33 (94%) patients reported good to excellent satisfaction. High BMI (≥27.5 kg/m2) and large lesion size (≥5.4 cm2) were found to be significant predictors of poor clinical and arthroscopic outcomes (P < .05 for both). Other prognostic factors, including patient age, sex, cartilage lesion location, and presence of subchondral cysts, did not significantly influence the outcomes (P > .05). Conclusion: The outcomes of MSC implantation for cartilage repair in OA knees seem encouraging; high BMI and large lesion size are important factors affecting outcomes. Although still in the early stages of application, MSC implantation for cartilage repair may have great potential for the treatment of OA knees. However, second-look arthroscopic findings revealed that 76% had the repair rated as abnormal or severely abnormal by ICRS standards. The development of an advanced surgical procedure with tissue-engineered scaffolds may be needed to treat patients with large cartilage lesions.

Clinical Outcomes of Mesenchymal Stem Cell Injection With Arthroscopic Treatment in Older Patients With Osteochondral Lesions of the Talus

Background: The ideal treatment for osteochondral lesions of the talus (OLTs) is still controversial, especially in older patients. Recently, mesenchymal stem cells (MSCs) have been suggested for use in the cell-based treatment of cartilage lesions. Purpose: To compare the clinical outcomes of MSC injection and arthroscopic marrow stimulation treatment with those of arthroscopic marrow stimulation treatment alone for the treatment of OLTs in older patients. Study Design: Cohort study; Level of evidence, 3. Methods: Among 107 patients with OLTs treated arthroscopically, only the patients older than 50 years (65 patients) were included in this study. Patients were divided into 2 groups: 35 patients (37 ankles) treated with arthroscopic marrow stimulation treatment alone (group A) and 30 patients (31 ankles) who underwent MSC injection along with arthroscopic marrow stimulation treatment (group B). Clinical outcomes were evaluated according to the visual analog scale (VAS) for pain, the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, and the Roles and Maudsley score. The Tegner activity scale was used to determine outcomes in activity levels. Results: The mean VAS score in each group was significantly improved (P < .05) from 7.2 ± 1.1 to 4.0 ± 0.7 in group A and from 7.1 ± 1.0 to 3.2 ± 0.9 in group B. The mean AOFAS score in each group was also significantly improved (P < .05) from 68.0 ± 5.5 to 77.2 ± 4.8 in group A and from 68.1 ± 5.6 to 82.6 ± 6.4 in group B. There were significant differences in mean VAS and AOFAS scores between the groups at final follow-up (mean, 21.8 months; range, 12-44 months) (P < .001). The Roles and Maudsley score showed significantly greater improvement in group B than in group A after surgery (P = .040). The Tegner activity scale score was significantly improved in group B (from 3.5 ± 0.7 to 3.8 ± 0.7; P = .041) but not in group A (from 3.5 ± 0.8 to 3.6 ± 0.6; P = .645). Large lesion size (≥109 mm2) and the existence of subchondral cysts were significant predictors of unsatisfactory clinical outcomes in group A (P = .04 and .03, respectively). These correlations were not observed in group B. Conclusion: Injection of MSCs with marrow stimulation treatment was encouraging in patients older than 50 years compared with patients treated with marrow stimulation treatment alone, especially when the lesion size was larger than 109 mm2 or a subchondral cyst existed. Although still in the early stages of application, MSCs may have great potential in the treatment of OLTs in patients older than 50 years, and more evaluations of its effect should be performed.

Factors Associated With the Clinical Outcomes of the Osteochondral Autograft Transfer System in Osteochondral Lesions of the Talus Second-Look Arthroscopic Evaluation

Background: Identifying factors associated with the clinical outcomes of the osteochondral autograft transfer system would be helpful for treating patients with an osteochondral lesion of the talus. Purpose: To investigate the clinical and second-look arthroscopic results of the osteochondral autograft transfer system and to identify the prognostic factors associated with this procedure. Study Design: Case series; Level of evidence, 4. Methods: The authors retrospectively evaluated 52 ankles that underwent osteochondral autograft transfer for a medial osteochondral lesion of the talus. Second-look arthroscopies were performed at a mean of 13.1 months postoperatively. Clinical outcomes were evaluated according to a visual analog scale (VAS) for pain, American Orthopaedic Foot and Ankle Society (AOFAS) score, and the Tegner activity scale. Statistical analyses were performed to identify various prognostic factors associated with the clinical outcomes. Results: The mean VAS, AOFAS, and Tegner activity scale scores were all significantly improved from 6.9 ± 0.9 to 3.3 ± 1.4 (VAS), from 67.4 ± 4.9 to 82.6 ± 7.8 (AOFAS), and from 3.0 ± 0.8 to 3.9 ± 0.9 (Tegner; P < .05). Regarding overall patient satisfaction with the operation, 49 (95%) patients reported good to excellent results. Prognostic factors including the patient’s age, sex, body mass index, duration of symptoms, defect size and depth, location of osteochondral lesion of the talus, and the existence of a subchondral cyst did not significantly influence clinical outcomes (P > .05), except for body mass index on the Tegner activity scale score (P = .021). Significant differences were observed among clinical outcomes for second-look arthroscopy according to the presence of soft tissue impingement and uncovered areas around the graft (P < .05). The VAS and AOFAS score at the last follow-up were significantly worse when the articular surface of the tibial plafond at the malleolar osteotomy site was uneven (P = .031 and .012, respectively). Conclusion: This study showed that the articular surface of the tibial plafond at the malleolar osteotomy site, soft tissue impingement, and uncovered areas around the graft were important factors affecting the clinical outcomes, as observed through second-look arthroscopy. Therefore, surgeons should restore the articular surface accurately after the osteotomy, and more caution should be taken to avoid soft tissue impingement and uncovered areas around the graft when performing osteochondral autograft transfer.

Mesenchymal Stem Cell Implantation in Knee Osteoarthritis An Assessment of the Factors Influencing Clinical Outcomes

Background: Several clinical studies have reported on cell-based treatment using mesenchymal stem cells (MSCs) for cartilage regeneration in knee osteoarthritis (OA). However, little is known about the factors that influence the clinical outcomes after surgery. Purpose/Hypothesis: This study aimed to investigate the clinical outcomes of MSC implantation in patients with knee OA and assess the factors that are associated with clinical outcomes. The hypothesis was that factors may exist that could influence clinical outcomes. Study Design: Case series; Level of evidence, 4. Methods: A total of 49 patients (55 knees) were retrospectively evaluated after MSC implantation for knee OA. The inclusion criteria were patients who had an isolated full-thickness cartilage lesion and Kellgren-Lawrence OA grade 1 or 2. Clinical outcomes were measured with the International Knee Documentation Committee (IKDC) score, Tegner activity score, and patients’ overall satisfaction with the surgery. Statistical analyses were performed to determine the effect of different factors on the clinical outcome. Results: The mean pre- and postoperative IKDC and Tegner activity scores significantly improved from 37.7 ± 6.3 to 67.3 ± 9.5 (IKDC) and from 2.2 ± 0.7 to 3.8 ± 0.7 (Tegner) (P < .001 for both). Twenty-four patients reported their overall satisfaction with the surgery as excellent (43.6%), 17 as good (30.9%), 11 as fair (20.0%), and 3 as poor (5.5%). There were significant differences in clinical outcomes at the final follow-up among the age and lesion size groups (P < .05 for all). Multivariate analyses showed high prognostic significance related to patient age and lesion size, and scatter plots suggested a cutoff age of 60 years and a cutoff lesion size of 6.0 cm2 for the optimum identification of poor clinical outcomes (P < .05 for both). Conclusion: The clinical outcomes of MSC implantation for knee OA are encouraging. Patient age and lesion size are important factors that affect clinical outcomes; thus, these may serve as a basis for preoperative surgical decisions. Cutoff points exist for the risk of clinical failure in patients older than 60 years and those with a lesion size larger than 6.0 cm2.

Does an Injection of a Stromal Vascular Fraction Containing Adipose-Derived Mesenchymal Stem Cells Influence the Outcomes of Marrow Stimulation in Osteochondral Lesions of the Talus? A Clinical and Magnetic Resonance Imaging Study

Background: Marrow stimulation for the treatment of osteochondral lesions of the talus (OLTs) is controversial in patients with poor prognostic factors of OLTs. Currently, mesenchymal stem cells (MSCs) are expected to biologically augment the treatment of OLTs. Purpose: To compare the clinical and magnetic resonance imaging (MRI) outcomes between an injection of MSCs with marrow stimulation and marrow stimulation alone in patients with OLTs. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 49 patients (50 ankles) with OLTs underwent follow-up MRI after arthroscopic treatment. Among these 50 ankles, 26 underwent marrow stimulation alone (conventional group), and 24 underwent marrow stimulation with an injection of a stromal vascular fraction (SVF) containing MSCs (MSC group). Clinical outcomes were evaluated according to the visual analog scale (VAS) for pain, American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, and Tegner activity scale. The magnetic resonance observation of cartilage repair tissue (MOCART) score was used for the MRI evaluation of repaired lesions. Results: The mean VAS score, AOFAS score, and Tegner score improved from 7.1 ± 1.2, 68.5 ± 5.6, and 3.4 ± 0.6 to 3.9 ± 0.8, 78.3 ± 4.9, and 3.5 ± 0.8, respectively, in the conventional group and from 7.1 ± 0.8, 67.7 ± 4.7, and 3.4 ± 0.5 to 3.2 ± 0.8, 83.3 ± 7.0, and 3.9 ± 0.7, respectively, in the MSC group. All clinical outcomes, including the VAS, AOFAS, and Tegner scores, improved significantly in the MSC group compared with the conventional group (P = .003, .009, and .041, respectively). There was a significant difference (P = .037) in the mean MOCART score between the conventional and MSC groups (49.4 ± 16.6 vs 62.1 ± 21.8, respectively), and significant correlations of the MOCART score with clinical outcomes were found in both groups (P < .05). Patient age (≥46.1 years), large lesion size (≥151.2 mm2), and the presence of subchondral cysts were associated with a worse MOCART score in the conventional group (P = .015, .004, and .013, respectively) but not in the MSC group. Conclusion: Clinical and MRI outcomes of an injection of an SVF containing MSCs with marrow stimulation were encouraging, compared with marrow stimulation alone, for the treatment of OLTs. Therefore, an injection of an SVF containing MSCs with marrow stimulation should be considered as a treatment for OLTs, even when poor prognostic factors, including older age, large-sized lesion, or the presence of subchondral cysts, exist.

Comparative Matched-Pair Analysis of the Injection Versus Implantation of Mesenchymal Stem Cells for Knee Osteoarthritis

Background: The mesenchymal stem cell (MSC)–based tissue engineering approach has been developed to address the problem of articular cartilage repair in knee osteoarthritis (OA). However, the most effective method of MSC application has not yet been established. Purpose: To compare the injection and implantation of MSCs in patients with knee OA in terms of clinical and second-look arthroscopic outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: Among 182 patients treated with arthroscopic surgery using MSCs for knee OA from October 2010 to August 2012, patients treated with an injection of MSCs in combination with platelet-rich plasma (injection group; n = 20) were pair-matched with patients who underwent MSC implantation on a fibrin glue scaffold (implantation group; n = 20) based on sex, age, and lesion size. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) score and Tegner activity scale, and cartilage repair was assessed arthroscopically with the International Cartilage Repair Society (ICRS) grading system. Results: The mean (±SD) IKDC and Tegner activity scores significantly improved from 38.5 ± 9.2 to 55.2 ± 15.0 and from 2.5 ± 1.2 to 3.5 ± 1.2, respectively, in the injection group and from 36.6 ± 4.9 to 62.7 ± 14.1 and from 2.3 ± 0.9 to 3.6 ± 1.1, respectively, in the implantation group at the time of second-look arthroscopic surgery (mean, 12.6 months postoperatively) (P < .001 in all cases). At final follow-up (mean, 28.6 months postoperatively), the mean IKDC and Tegner activity scores in the implantation group had improved further to 64.8 ± 13.4 and 3.9 ± 1.0, respectively (P < .001 and P = .035, respectively), while no significant improvements were found in the injection group (P = .130 and P = .655, respectively). At final follow-up, there was a significant difference in the mean IKDC score between groups (P = .049). Significant correlations between the number of administered MSCs and the postoperative clinical outcomes were found only in the injection group. Significant correlations between the clinical outcomes and the ICRS grades were found in both groups. The ICRS grades were significantly better in the implantation group (P = .041). In the injection group, 2 of the 20 lesions (10%) were grade I (normal), 5 (25%) were grade II (near normal), 8 (40%) were grade III (abnormal), and 5 (25%) were grade IV (severely abnormal). In the implantation group, 6 of the 20 lesions (30%) were grade I, 7 (35%) were grade II, 4 (20%) were grade III, and 3 (15%) were grade IV. Conclusion: Utilizing the described method, MSC implantation for knee OA resulted in better clinical and second-look arthroscopic outcomes than an MSC injection.

Characterization of adipose tissue-derived stromal vascular fraction for clinical application to cartilage regeneration.

Bone marrow concentration (BMC) is the most recognized procedure to prepare mesenchymal stem cells for cartilage regeneration. However, bone marrow aspiration is highly invasive and results in low stem cell numbers. Recently, adipose tissue-derived stromal vascular fraction (AT-SVF) was studied as an alternate source of stem cells for cartilage regeneration. However, AT-SVF is not fully characterized in terms of functional equivalence to BMC. Therefore, in this study, we characterized AT-SVF and assessed its suitability as a one-step surgical procedure for cartilage regeneration, as an alternative to BMC. AT-SVF contained approximately sixfold less nucleated cells than BMC. However, adherent cells in AT-SVF were fourfold greater than BMC. Additionally, the colony-forming unit frequency of AT-SVF was higher than that of BMC, at 0.5 and 0.01%, respectively. The mesenchymal stem cell (MSC) population (CD45−CD31−CD90+CD105+) was 4.28% in AT-SVF and 0.42% in BMC, and the adipose-derived stromal cell (ASC) population (CD34+CD31−CD146−) was 32% in AT-SVF and 0.16% in BMC. In vitro chondrogenesis demonstrated that micromass was not formed in BMC, whereas it was clearly formed in AT-SVF. Taken together, uncultured AT-SVF could be used in one-step surgery for cartilage regeneration as a substitute for BMC.

Supramalleolar Osteotomy With Bone Marrow Stimulation for Varus Ankle Osteoarthritis Clinical Results and Second-Look Arthroscopic Evaluation

Background: Supramalleolar osteotomy (SMO), which redistributes the load line within the ankle joint, has been reported as an effective treatment for varus ankle osteoarthritis. However, no study has examined cartilage regeneration in the medial compartment of the ankle after SMO. Hypothesis/Purpose: This study aimed to investigate the clinical and radiological outcomes of SMO and to identify the association between the outcomes of SMO and cartilage regeneration evaluated by second-look arthroscopy. The hypothesis was that cartilage regeneration would be an important predictor of the outcomes of SMO and that arthroscopic marrow stimulation would aid in cartilage regeneration. Study Design: Case series; Level of evidence, 4. Methods: A total of 31 ankles were retrospectively evaluated after arthroscopic marrow stimulation with SMO for varus ankle osteoarthritis; second-look arthroscopy was conducted for all these ankles. Clinical outcome measures included a visual analog scale (VAS) for pain and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Radiological outcome variables included the tibial-ankle surface angle (TAS), talar tilt (TT), and tibial-lateral surface angle (TLS), and progression of degenerative arthritis of the ankle was assessed. In the second-look arthroscopy, cartilage regeneration was evaluated using the International Cartilage Repair Society (ICRS) grade. Results: The mean ± standard deviation VAS and AOFAS scores were 7.1 ± 0.8 and 62.9 ± 4.0 preoperatively, and they significantly improved to 3.4 ± 1.3 and 83.1 ± 7.5, respectively (P < .001, for both) at the time of the second-look arthroscopy (mean, 13.2 months postoperatively). However, at final follow-up (mean, 27.4 months postoperatively), they were significantly decreased to 4.1 ± 1.6 and 79.9 ± 8.0, respectively, compared with the values at second-look arthroscopy (P < .001, for both). The mean TAS, TT, and TLS improved significantly after SMO but showed no significant correlation with the clinical outcomes and ICRS grade (P > .05 for all three). At second-look arthroscopy, the ICRS overall repair grades were normal in 1 (3%), nearly normal in 7 (23%), abnormal in 13 (42%), and severely abnormal in 10 (32%). Progressive degenerative arthritis was observed in 13 cases (42%). The ICRS grade was significantly associated with the clinical outcomes (P < .0001) and development of degenerative arthritis of the ankle joint (P = .002). Conclusion: This study showed improved clinical outcomes after SMO for varus ankle osteoarthritis in comparison to the preoperative assessments. Furthermore, the ICRS grade was significantly associated with the clinical outcomes of SMO at final follow-up and significantly associated with the development of degenerative arthritis of the ankle joint. Therefore, arthroscopic marrow stimulation should be considered with SMO to ensure adequate cartilage regeneration. However, given the ICRS grades observed at the time of the second-look arthroscopies and the progression of degenerative arthritis in 42%, the long-term prognosis in this group of patients is uncertain.

Clinical Comparison of the Osteochondral Autograft Transfer System and Subchondral Drilling in Osteochondral Defects of the First Metatarsal Head

Background: Osteochondral defects of the first metatarsal head can deteriorate to osteoarthritis of the first metatarsophalangeal joint if left untreated. Treatment options for osteochondral defects of the first metatarsal head vary widely. Purpose: To compare the clinical outcomes of the osteochondral autograft transfer system with those of subchondral drilling for the treatment of osteochondral defects of the first metatarsal head. Study Design: Cohort study; Level of evidence, 3. Methods: The authors retrospectively evaluated 24 cases of osteochondral defects of the first metatarsal head treated operatively; 14 patients underwent subchondral drilling (group A), while 10 were treated with the osteochondral autograft transfer system (group B). The association of variables of osteochondral defects with clinical outcomes was assessed in each group. Clinical outcomes were evaluated according to a visual analog scale (VAS) for pain, the American Orthopaedic Foot and Ankle Society (AOFAS) hallux metatarsophalangeal-interphalangeal scale, and the Roles and Maudsley score. The Tegner activity scale and an activity rating scale were used to determine the activity levels. Results: The mean VAS score in both groups was significantly improved (from 6.9 ± 0.9 to 3.9 ± 1.3 in group A and from 7.4 ± 0.8 to 3.4 ± 1.2 in group B; P < .05). No difference was noted between the 2 groups at final follow-up (P = .651). The mean AOFAS score in both groups was significantly improved (from 62.9 ± 5.8 to 73.2 ± 8.2 in group A and from 65.0 ± 4.1 to 81.5 ± 5.8 in group B; P < .05). There was a significant difference in mean AOFAS score between the 2 groups at final follow-up (P = .032). Large defect size (≥50 mm2) and the existence of a subchondral cyst were significant predictors of unsatisfactory clinical outcomes in group A (P = .047 and P = .019, respectively). Multivariate analyses showed a defect size larger than 50 mm2 was associated with significantly worse outcomes on the last follow-up VAS and AOFAS scores in group A (P = .005 for VAS and P = .006 for AOFAS). There was no association of defect size and subchondral cyst with clinical outcomes in group B (P > .05). No association was found between location of the defect area and clinical outcome in either group. Conclusion: For osteochondral defects larger than 50 mm2 or when a subchondral cyst exists, the osteochondral autograft transfer system could potentially be used as a treatment of choice for osteochondral defects of the first metatarsal head to restore functionality of the metatarsophalangeal joint.