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Abstract Background Interleukin (IL)-17 is an important factor in rheumatoid arthritis (RA) pathogenesis. MicroRNA (miRNA)s are a family of non coding RNAs and associated with human diseases including RA. The purpose of this study is to identify the miRNAs in the differentiation of IL-17 producing cells, and analyze their expression pattern in the peripheral blood mononuclear cells (PBMC) and synovium from RA patients. Methods IL-17 producing cells were expanded from CD4+T cell. MiRNA microarray was performed to identify the miRNAs in the differentiation of IL-17 producing cells. Quantitative polymerase chain reaction was performed to examine the expression patterns of the identified miRNAs in the PBMC and synovium from RA and osteoarthritis (OA) patients. Double staining combining in situ hybridization and immunohistochemistry of IL-17 was performed to analyze the expression pattern of identified miRNA in the synovium. Results Six miRNAs, let-7a, miR-26, miR-146a/b, miR-150, and miR-155 were significantly up regulated in the IL-17 producing T cells. The expression of miR-146a and IL-17 was higher than in PBMC in the patients with low score of Larsen grade and short disease duration. MiR-146a intensely expressed in RA synovium in comparison to OA. MiR-146a expressed intensely in the synovium with hyperplasia and high expression of IL-17 from the patients with high disease activity. Double staining revealed that miR-146a expressed in IL-17 expressing cells. Conclusion These results indicated that miR-146a was associated with IL-17 expression in the PBMC and synovium in RA patients. There is the possibility that miR-146a participates in the IL-17 expression.

This study evaluated factors affecting sensory restoration after thumb reconstruction using a wrap-around flap in 21 thumbs in patients aged 11 to 50 years old. The patients were followed from 12 to 94 months after surgery. Static and moving 2-point discrimination of the reconstructed pulp was measured and analysed using multiple regression analysis. According to the univariate and multivariate analyses, the preoperative period, the number of nerve coaptations, and the duration of follow-up all significantly affected sensory recovery. Sensory recovery with more than three coaptations was significantly better than those with less than three coaptations, and the number of nerve coaptations was one of the primary factors influencing sensory recovery. We conclude from this study that the wrap-around flap should be performed soon after injury and that surgeons should try to coaptate three or more nerves to enhance sensory recovery. Level of evidence: IV [ABSTRACT FROM AUTHOR]

The purpose of this study is to clarify the kinetics of transplanted mesenchymal stem cells (MSCs) in rat skeletal muscle injury model and the contribution of the magnetic cell delivery system to muscle injury repair. A magnetic field generator was used to apply an external magnetic force to the injury site of the tibia anterior muscle, and 1 × 106 MSCs labeled with ferucarbotran-protamine complexes, which were isolated from luciferase transgenic rats, were injected into the injury site. MSCs were injected with and without an external magnetic force (MSC M+ and MSC M− groups, respectively), and phosphate-buffered saline was injected into injury sites as a control. In vivo bioluminescence imaging was performed immediately after the transplantation and, at 12, 24, and 72 h, and 1 and 4 weeks post-transplantation. Also, muscle regeneration and function were histologically and electromechanically evaluated. In vivo bioluminescence imaging showed that the photon of the MSC M+ group was significantly higher than that of the MSC M− group throughout the observation period. In addition, muscle regeneration and function in the MSC M+ group was histologically and functionally better than that of the MSC M− group. The results of our study indicated that magnetic cell delivery system may be of use in directing the transplanted MSCs to the injury site to promote skeletal muscle regeneration. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 754-759, 2013 [ABSTRACT FROM AUTHOR]

Chung Y-G, Bishop AT, Giessler GA, Suzuki O, Platt JL, Pelzer M, Friedrich PF, Kremer T. Surgical angiogenesis: a new approach to maintain osseous viability in xenotransplantation. Xenotransplantation 2010; 17: 38–47. © 2010 John Wiley & Sons A/S. Large segmental osseous defects are challenging clinical problems. Current reconstructive methods, using non-viable allografts, vascularized autografts or prostheses have significant rates of serious complications and failure. These include infection, stress fracture and non-union (frozen structural allogenic bone); loosening and implant failure (prosthetic replacement); limited availability, poor match of size and shape and donor site morbidity (vascularized autograft bone). In the future, microvascular transplantation of living allogenic or xenogenic bone could solve some of these issues, combining the advantages of living bone autografts (capability of primary osseous healing, remodeling, and fracture resistance) with the ability to match size and shape, provide immediate stability and avoid donor site morbidity. Xenotransplants would be particularly attractive, as they could be readily available, if long-term bone survival could be achieved without unacceptable morbidity. Here, we present a preliminary study to evaluate a new and unique method to maintain xenogenic bone circulation without need for long-term immune modulation that depends upon generation of a neo-angiogenic circulation within the transplanted bone from recipient-derived vessels. Thus, only short-term immunosuppression would be required to achieve bone survival. Methods: One hundred and forty-one hamster femora were microsurgically transplanted to rats, restoring nutrient vessel circulation with standard microvascular anastomoses. At the same time, a host-derived arteriovenous bundle (AVB) was placed within the medullary canal. Two independent variables were evaluated: use of tacrolimus/cyclophosmamid immunosuppression (IS) and patency of the implanted AVB. Rats were therefore randomized to four groups; group 1—no IS + patent AVB; group 2—no IS + ligated AVB; group 3—IS + patent AVB; group 4—IS + ligated AVB. Rats were sacrificed after 1 or 2 weeks. We evaluated bone blood flow (microsphere entrapment), neoangiogenesis (microangiography and quantification of capillary density), bone necrosis rate (osteocyte counts) and nutrient pedicle rejection (microsurgical anastomotic patency). Statistical Analysis was performed with two-way ANOVA with Bonferroni adjustment. Differences were considered significant when P < 0.05. Results: Capillary density was significantly increased with a patent intramedullary AVB (groups 1/3) compared to groups with ligated AVBs (groups 3/4). Capillary sprouting was predominantly restricted to the endosteal layer. Most nutrient pedicles (78.7%) stayed patent in groups with IS (groups 3 and 4). Consequently, bone blood flow was significanty higher in groups 3 and 4 compared to groups 1 and 2. Similary, a patent AV bundle improved flow in group 1 when compared to group 2. The bone necrosis rate was not influenced by the presence of patent AVBs but was significantly reduced in groups 3 and 4. Conclusions: Surgical angiogenesis occurs when patent arteriovenous bundles are placed in the medullary canal of xenogenic bone and leads to increased bone blood flow. Bone viability was not significantly influenced by neoangiogenesis. Although capillary sprouting was restricted to the endosteal layer in this short term study, more complete cortical revascularization might be observed in a long-term study. Such a study should further evaluate whether these new vessels supply sufficient blood flow to maintain long-term bone viability and allow remodeling. [ABSTRACT FROM AUTHOR]

Background Platelets contain many kinds of growth factors with the ability to accelerate angiogenesis. We analyzed whether a single injection of platelet-rich plasma (PRP) would accelerate surgical angiogenesis in necrotic bone implanted with vascular tissue. Methods We used 24 Japanese White rabbits. PRP was refined from autologous blood by separation twice with centrifugation. A removed iliac bone was frozen in liquid nitrogen to ensure complete cellular necrosis. A narrow hole was made in the bone and the saphenous vascular bundle was passed through the hole. The bone was wrapped after injection of either 1 mL (1) PRP, or (2) saline solution into the hole, and was placed subcu-taneously in the thigh. In both groups, angiogenesis was compared 1 week and 2 weeks after surgery. Result Angiogenesis was observed along the implanted vascular bundle in both groups. At 1 and 2 weeks after surgery, both the vessel density and the average length of newly formed vessels of the experimental group were significantly greater than in the control group. Both the vessel density and the length were greater after 2 weeks than after 1 week. Interpretation A single injection of PRP accelerates surgical angiogenesis in vascular-implanted necrotic bone. [ABSTRACT FROM AUTHOR]

Purpose: We performed radius lengthening to treat radial deviation of the wrist in patients with Bayne and Klug type II and type III radial longitudinal deficiencies. The purpose of this investigation was to review our results of radius lengthening for radial longitudinal deficiency. Methods: Beginning in 1991 radius lengthening was performed to treat 4 patients with radial longitudinal deficiency whose mean age at the initial lengthening was 16 months. The corrections for radial deviation of the wrists were performed simultaneously by soft-tissue distraction of the wrist. According to Bayne and Klug’s classification 2 patients had type II and 2 patients had type III deficiencies. All but 1 patient had lengthening several times to correct the recurring discrepancy between the radius and the ulna. Results: The corrections were achieved just after the lengthening but deformities recurred because of growth discrepancies between the radius and the ulna as the children grew. The radius was lengthened by a mean of 28 mm, with a mean length gain of 79%. The mean period in the fixator was 136 days. Two patients had both functionally and cosmetically acceptable correction after several lengthening procedures. In the other patient we abandoned this treatment method because of severe bone absorption at the distal end of the lengthened radius. One patient died of cardiac disease after one lengthening. Conclusions: Radius lengthening for Bayne and Klug type II and type III deficiencies may be accomplished successfully with the primary benefit of maintaining wrist and forearm motion. It is likely that at least 3 lengthenings may be required and this may need to be accompanied by a soft-tissue distraction at the ulnar carpal joint as well. Type of study/level of evidence: Therapeutic, Level IV. [Copyright &y& Elsevier]

The aim of this study was to accelerate angiogenesis in necrotic bone by combining vascular bundle implantation and fibroblast growth factor-2 (FGF-2) administration.Twenty-four Japanese white rabbits were evaluated in this study. A portion of a rabbit iliac crest bone was removed as a free bone graft and frozen in liquid nitrogen to ensure complete cellular necrosis. A narrow hole was created in the bone and the graft was placed in the proximal thigh. In group 1, FGF-2 was injected into the hole at a single dose of 100 μg, and the saphenous artery and its venae comitantes were passed through the hole of the bone. In group 2, injection of saline into the hole and the vascular bundle implantation was used as a control. Neovascularization around the vessel was evaluated at weeks 1 and 2 after surgery.Neovascularization was observed along the implanted vascular bundle in both groups. At both 1 and 2 weeks after surgery, the vessel density of group 1 was significantly higher than that of group 2. The average length of newly formed vessels of group 1 was also significantly longer than that of group 2 at both 1 and 2 weeks after surgery. Both the vessel density and length were greater in week 2 animals than week 1.A local single injection of FGF-2 improved surgical angiogenesis in necrotic bone in this study. As FGF-2 is recognized as a potent mitogen for a variety of mesenchymal cells, the combination of vascular bundle implantation and FGF-2 administration may contribute to the treatment of ischemic osteonecrosis. [Copyright &y& Elsevier]

This study evaluated factors affecting sensory restoration after thumb reconstruction using a wrap-around flap in 21 thumbs in patients aged 11 to 50 years old. The patients were followed from 12 to 94 months after surgery. Static and moving 2-point discrimination of the reconstructed pulp was measured and analysed using multiple regression analysis. According to the univariate and multivariate analyses, the preoperative period, the number of nerve coaptations, and the duration of follow-up all significantly affected sensory recovery. Sensory recovery with more than three coaptations was significantly better than those with less than three coaptations, and the number of nerve coaptations was one of the primary factors influencing sensory recovery. We conclude from this study that the wrap-around flap should be performed soon after injury and that surgeons should try to coaptate three or more nerves to enhance sensory recovery. Level of evidence: IV.

Object: CD133(+) cells have the potential to enhance histological and functional recovery from peripheral nerve injury. However, the number of CD133(+) cells safely obtained from human peripheral blood is extremely limited. To address this issue, the authors expanded CD133(+) cells derived from human peripheral blood using the serum-free expansion culture method and transplanted these ex vivo expanded cells into a model of sciatic nerve defect in rats. The purpose of this study was to determine the potential of ex vivo expanded CD133(+) cells to induce or enhance the repair of injured peripheral nerves., Methods: Phosphate-buffered saline (PBS group [Group 1]), 10(5) fresh CD133(+) cells (fresh group [Group 2]), 10(5) ex vivo expanded CD133(+) cells (expansion group [Group 3]), or 10(4) fresh CD133(+) cells (low-dose group [Group 4]) embedded in atelocollagen gel were transplanted into a silicone tube that was then used to bridge a 15-mm defect in the sciatic nerve of athymic rats (10 animals per group). At 8 weeks postsurgery, histological and functional evaluations of the regenerated tissues were performed., Results: After 1 week of expansion culture, the number of cells increased 9.6 ± 3.3-fold. Based on the fluorescence-activated cell sorting analysis, it was demonstrated that the initial freshly isolated CD133(+) cell population contained 93.22% ± 0.30% CD133(+) cells and further confirmed that the expanded cells had a purity of 59.02% ± 1.58% CD133(+) cells. However, the histologically and functionally regenerated nerves bridging the defects were recognized in all rats in Groups 2 and 3 and in 6 of 10 rats in Group 4. The nerves did not regenerate to bridge the defect in any of the rats in Group 1., Conclusions: The authors' results show that ex vivo expanded CD133(+) cells derived from human peripheral blood have a therapeutic potential similar to fresh CD133(+) cells for peripheral nerve injuries. The ex vivo procedure that can be used to expand CD133(+) cells without reducing their function represents a novel method for developing cell therapy for nerve defects in a clinical setting.

Background: Indications for pollicization of the index finger have decreased since the toe-to-thumb transfer and wraparound flap have been developed for thumb reconstruction. Pollicization, however, remains a useful method of thumb reconstruction depending on the amputation level, age, and patients' requests. The purpose of this study was to evaluate the authors' results and to clarify indications for pollicization., Methods: Eight patients treated by pollicization of the index finger after thumb amputation were reviewed retrospectively. Five men and three women were included. The age at surgery ranged from 24 to 66 years, with a mean age of 43 years. Amputation levels included the metacarpophalangeal joint in four patients, the first metacarpal in three, and the carpometacarpal joint in one. The period between injury and pollicization ranged from 0 days to 4 years. Postoperative evaluations included thumb range of motion, opposition and pinch function, grasp and pinch strength, sensation, conversion of position sense, a "picking-up" test, and appearance., Results: The follow-up period ranged from 5 to 28 years, with an average of 15 years, excluding one patient who died during the follow-up period. The thenar muscles were retained in four patients, who had excellent postoperative function and satisfactory results., Conclusions: Pollicization gives excellent results if the thenar muscles can be retained; opposition can be expected after this procedure. However, if the thenar muscles cannot be preserved, the reconstructed thumb may function as a post against the fingers to regain grasping and pinching functions.

Objective: The purpose of this study was to determine whether 3-dimensional (3D) computed tomography (CT) imaging with volume rendering can accurately evaluate extensor tendons in the hand and wrist., Methods: Three-dimensional CT imaging was used to evaluate 14 cases. The location where the rupture was suspected was the wrist level in all cases. The accuracy of the image diagnosis was confirmed during surgery in 13 cases., Results: Three-dimensional CT could identify all extensor tendons proximal to the metacarpophalangeal joint. In the cases with rupture, the location of the distal stump could be identified, whereas that of the proximal stump was uncertain. The tendon stump location confirmed during surgery correlated well with the images., Conclusions: This study revealed the usefulness of 3D CT imaging in defining extensor tendons proximal to the metacarpophalangeal joint. This method increased the accuracy and ease of diagnosis and was always useful in surgical planning and patient education.

The ability of vascular endothelial growth factor (VEGF) to accelerate neoangiogenesis from implanted arterovenous (AV) bundles in necrotic bone was evaluated. A saphenous AV bundle was placed in a necrotic segment of rabbit ilium. In group II, VEGF (100 ng/h x 3 days) was administered by continuous infusion. Bone blood flow was measured with radioactive-labeled microspheres, and capillary density was determined by microangiography combined with Spälteholtz bone clearing at 1, 2, and 4 weeks. Neovascularization was observed along the implanted vascular bundle in both groups. One week after surgery, bone blood flow and vessel area were significantly higher in VEGF-treated animals (P < 0.05). No significant difference was observed at later times. Direct VEGF administration increased surgical angiogenesis and improved blood flow and neovascularization in necrotic bone 1 week after AV bundle implantation. Thereafter, a robust angiogenic response from the AV bundle was seen in both groups., (Copyright 2004 Wiley-Liss, Inc.)