Chris Hyunchul Jo

Mesenchymal Stem-Cell Transplantation for Hypoxic-Ischemic Brain Injury in Neonatal Rat Model

Neonatal hypoxic-ischemic brain injury (HIE) remains a major cause of neurologic disabilities. However, many experimental therapies have shown limited successes. We assessed whether human mesenchymal stem cells (MSCs) could be transplanted in the HIE rat brain to improve neurologic disabilities. P7 SD rats were either subjected to left carotid artery ligation and hypoxic exposure [hypoxia-ischemia (HI)] or sham operation and normoxic exposure (sham). On P10, rat pubs received either PKH26-labeled MSCs or buffer via intracardial injection, resulting in four experimental groups: sham-buffer, sham-MSC, HI-buffer, and HI-MSC. Cylinder test and accelerating rotarod test were performed 14, 20, 30, and 40 d after injection. Six weeks after injection, cresyl violet and double immunofluorescence staining were performed. MSCs were transplanted to the whole brain mainly after HI. Glial fibrillary acidic protein and OX42 were more abundantly colocalized with MSC than neuronal specific nuclear protein or myelin basic protein. There were no significant differences in the total amounts and cell types between the lesioned and nonlesioned hemisphere. The lesioned hemispheric volume was decreased after HI (p = 0.012) but not restored by MSC. Neurologic performance was significantly impaired only on the cylinder test after HI (p = 0.034), and MSC transplants improved it (p = 0.010). These suggest MSC can be a candidate for the treatment of neonatal HIE.

The slippage-proof knot: a new, nonstacking, arthroscopic, sliding locking knot with a lag bight.

The slippage-proof knot is a new, nonstacking, arthroscopic, sliding knot with a lag bight. The knot is easy to tie and ensures smooth sliding and avoidance of premature locking.

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

Comparative study of unilateral and bilateral cages with respect to clinical outcomes and stability in instrumented posterior lumbar interbody fusion.

OBJECTIVEnWe sought to compare the clinical and radiological results of instrumented posterior lumbar interbody fusion (PLIF) using unilateral or bilateral polyetheretherketone cages and pedicle screws.nnnMETHODSnOne hundred eighty-seven cases of degenerative spine that had been followed for at least 18 months were reviewed retrospectively. In 88 cases (147 levels), one cage was inserted, and in 99 cases (152 levels), two cages were inserted. Visual analog scale, Oswestry disability index, and functional rating indices were measured. Lumbar lordosis, lumbar scoliotic and fusion level scoliotic angles, and stable fixation were determined before surgery and 12 months postoperatively on standing x-rays. Amounts of intra- and postoperative blood loss, total quantities transfused, and operation times were also evaluated.nnnRESULTSnNo significant differences were found between the two groups in terms of visual analog scale, Oswestry disability index, functional rating indices, lumbar lordosis, lumbar scoliotic angles, fusion level scoliotic angles, or fixation stabilities. However, the amounts of postoperative blood loss, total blood loss, and total transfusion for two-level PLIF using a unilateral cage were statistically smaller than those for two-level PLIF using bilateral cages. Times required for PLIF using a unilateral cage were also significantly shorter than those for PLIF using bilateral cages.nnnCONCLUSIONnUnilateral cage and bilateral pedicle screw insertion may be a good alternative surgical option because it provides adequate alignment, balance, and mechanical stability in addition to reducing operative time, blood loss, and transfusion requirements.

Effect of intraoperative position used in posterior lumbar interbody fusion on the maintenance of lumbar lordosis

OBJECTnThe objective in this study was to compare retrospectively the use of different operating tables with different positions for posterior lumbar interbody fusion (PLIF) and the effect on intraoperative and postoperative lumbar lordosis and segmental lordosis.nnnMETHODSnOne hundred seventy-two patients with degenerative disease of the lumbar spine who underwent posterior decompression and PLIF in which a 0 degrees polyetheretherketone cage and pedicle screw fixation were used were evaluated. Ninety-one patients underwent surgery on a Wilson table (Group I) and 81 patients were treated on an OSI Jackson spinal table (Group II). Preoperative standing, intraoperative prone, and postoperative standing lateral radiographs were obtained in each patient. The total lumbar and segmental lordosis were compared and analyzed according to the position in which the patients were placed for their operation.nnnRESULTSnThe intraoperative total lumbar lordosis was significantly decreased compared with the preoperative value. The postoperative total lumbar lordosis was similar, however, to the preoperative values in both groups. In Group I, the intraoperative segmental lordosis of L2-3 and L3-4 was significantly decreased compared with the pre-operative segmental lordosis. In Group II, the intraoperative segmental lordosis of L3-4, L4-5, L5-S1, and L4-S1 was significantly decreased compared with the preoperative segmental lordosis. The postoperative segmental lordosis of L4-5 was significantly decreased and L2-3 was significantly increased compared with the preoperative lordosis in both groups.nnnCONCLUSIONSnIntraoperative position does not affect postoperative total lumbar lordosis and segmental lordosis in short-segment PLIF of the lumbar spine in a retrospective analysis of the surgical procedure to maintain lordosis.

Effects of Platelet-Rich Plasma With Concomitant Use of a Corticosteroid on Tenocytes From Degenerative Rotator Cuff Tears in Interleukin 1β–Induced Tendinopathic Conditions:

Background: A corticosteroid injection is commonly used to treat tendinopathy, but it has been associated with negative effects on tendon homeostasis. Platelet-rich plasma (PRP) is known to have proliferative and anabolic effects as well as cytoprotective effects against corticosteroids on tenocytes. However, the combined effects of a corticosteroid and PRP on the anti-inflammatory, matrix synthesis, and cytoprotective potential of tenocytes in conditions simulating tendinopathy have not been investigated. Purpose: To assess the effects of PRP on tenocytes from degenerative rotator cuff tears with the concomitant use of a corticosteroid in interleukin 1β (IL-1β)–induced tendinopathic conditions. Study Design: Controlled laboratory study. Methods: Tenocytes were enzymatically isolated and cultured from patients with degenerative rotator cuff tears. PRP was prepared using a plateletpheresis system, and growth factor concentrations were measured. To evaluate the gene expression of proinflammatory and anti-inflammatory cytokines, enzymes and their inhibitors, and matrix molecules, cells were cultured with 1 ng/mL IL-1β, 1 μM dexamethasone, and 10% (vol/vol) platelet-poor plasma (PPP) and PRP of 200, 1000, and 4000 × 103/μL; quantitative real-time reverse transcriptase polymerase chain reaction was also performed. Western blotting was performed to investigate the protein synthesis of degradative enzymes and their inhibitors. Cell viability, apoptosis, and senescence assays were also conducted. Results: PRP did not interfere with the anti-inflammatory effects of dexamethasone on tenocytes pretreated with IL-1β, but it increased the synthesis of tissue inhibitor of metalloproteinase (TIMP)–1 and -3. Meanwhile, PRP did not induce anti-inflammatory cytokines that had been suppressed with a corticosteroid. It did increase the type I/III collagen ratio mainly through the suppression of type III collagen expression. PRP reversed the decreased viability, increased apoptosis, and induced senescence with IL-1β and a corticosteroid. Conclusion: This study shows that the addition of PRP does not interfere with the anti-inflammatory effects of a corticosteroid on IL-1β–treated tenocytes from degenerative rotator cuff tears but that it does avoid the deleterious side effects of a corticosteroid. Clinical Relevance: PRP can be clinically useful with a corticosteroid as a treatment for tendinopathy.

Anterior capsular abnormality: another important MRI finding for the diagnosis of adhesive capsulitis of the shoulder

ObjectiveTo evaluate the usefulness of anterior capsular abnormality, thickening, and abnormal signal intensity on MRI for the diagnosis of adhesive capsulitis of the shoulder.Materials and methodsThis retrospective study included 29 patients with adhesive capsulitis and 20 controls. Clinical criteria with significant restricted passive motion was used for the diagnosis of adhesive capsulitis. The anterior capsular thickness and signal intensity were evaluated on the thickest portion of anterior glenohumeral joint capsule, located deep to the subscapularis muscle. In addition, the previously known MR findings of adhesive capsulitis, such as humeral and glenoid capsular thickness in axillary recess, maximal axillary capsular thickness, and coracohumeral ligament thickness, were measured. The presence of humeral and glenoid capsular abnormal hyperintensity in axillary recess, abnormal hyperintensity, and obliteration of the subcoracoid fat triangle were also evaluated.ResultsAll MRI findings significantly differed between adhesive capsulitis and controls. Among MR findings, multivariable analysis showed that anterior capsular thickness, maximal axillary capsular thickness, and anterior capsular abnormal hyperintensity were variables that could differentiate adhesive capsulitis from the control group, with odds ratios of 7.97, 17.75, and 12.41, respectively (pu2009<u20090.05). In ROC analysis, the anterior capsular thickness showed high diagnostic performances with an AUC of 0.897. The cut-off value of anterior capsular thickness at 3.5xa0mm showed excellent diagnostic accuracy, with sensitivity of 68.97% and specificity of 100%.ConclusionsAnterior capsular abnormality, thickening, and abnormal hyperintensity can be used for the diagnosis of adhesive capsulitis of shoulder, in addition to previously known abnormal MRI findings.

Comparative Analysis of Platelet-rich Plasma Effect on Tenocytes from Normal Human Rotator Cuff Tendon and Human Rotator Cuff Tendon with Degenerative Tears

Background Platelet-rich plasma (PRP) stimulates cell proliferation and enhances matrix gene expression and synthesis. However, there have been no comparative study of the PRP effect on the normal and degenerative tenocytes. The purpose of this study was to compare the effect of PRP on tenocytes from normal and degenerative tendon. Methods Tendon tissues were obtained from patients undergoing arthroscopic repair (n=9) and from healthy donors (n=3). Tenocytes were cultured with 10% (vol/vol) platelet-poor plasma, PRP activated with calcium, and PRP activated with calcium and thrombin. The total cell number was assessed at days 7 and 14. The expressions of type I and III collagen, decorin, tenascin-C, and scleraxis were evaluated by quantitative real-time reverse transcriptase polymerase chain reaction. The total collagen and glycosaminoglycan (GAG) synthesis was evaluated at days 7 and 14. Results No differences were observed between the groups at day 7, but cell proliferation was remarkably increased in tenocytes from the degenerative tendon at day 14. In both tenocyte groups, the gene expressions of type I and III collagen were up-regulated. GAG synthesis was greater in the normal tendon, whereas the expressions of decorin and tenascin-C were increased in tenocytes from the degenerative tendon. Tenocytes from the degenerative tendon had higher fold-change of GAG synthesis and a lower collagen III/I ratio than normal tenocytes. Conclusions PRP promoted the cell proliferation and enhanced the synthesis of tendon matrix in both groups. PRP has a greater positive effect on cell proliferation, matrix gene expression and synthesis in tenocytes from degenerative tendon.

Theoretical prediction and validation of cell recovery rates in preparing platelet-rich plasma through a centrifugation

In the present study, we propose a theoretical framework to predict the recovery rates of platelets and white blood cells in the process of centrifugal separation of whole blood contained in a tube for the preparation of platelet-rich plasma. Compared to previous efforts to optimize or standardize the protocols of centrifugation, we try to further the physical background (i.e., based on the multiphase flow phenomena) of analysis to develop a universal approach that can be applied to widely different conditions. That is, one-dimensional quasi-linear partial differential equation to describe the centrifugal sedimentation of dispersed phase (red and white blood cells) in continuous phase (plasma) is derived based on the kinematic-wave theory. With the information of whole blood volume and tube geometry considered, it is possible to determine the positions of interfaces between supernatant/suspension and suspension/sediment, i.e., the particle concentration gradient in a tube, for a wide range of centrifugation parameters (time and acceleration). While establishing a theory to predict the recovery rates of the platelet and white blood cell from the pre-determined interface positions, we also propose a new correlation model between the recovery rates of plasma and platelets, which is found to be a function of the whole blood volume, centrifugal time and acceleration, and tube geometry. The present predictions for optimal condition show good agreements with available human clinical data, obtained from different conditions, indicating the universal applicability of our method. Furthermore, the dependence of recovery rates on centrifugal conditions reveals that there exist a different critical acceleration and time for the maximum recovery rate of platelets and white blood cells, respectively. The other parameters such as hematocrit, whole blood volume and tube geometry are also found to strongly affect the maximum recovery rates of blood cells, and finally, as a strategy for increasing the efficiency, we suggest to dilute the whole blood, increase the whole blood volume with a tube geometry fixed.