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Background: During anterior cruciate ligament (ACL) reconstruction, even when a posterior wall of the femoral bone tunnel is identified, computed tomography (CT) occasionally demonstrates a breach of the posterior femoral cortex of the femoral bone tunnel, i.e., posterior wall blowout, after ACL reconstruction (posterior wall blowout-like phenomenon). This study aimed to investigate the influence of the posterior wall blowout-like phenomenon on clinical outcomes after ACL reconstruction using hamstring tendon., Methods: A total of 105 patients who underwent CT examination two weeks after ACL reconstruction were enrolled. A cortical suspension device was used for femoral side fixation in all cases. Posterior wall was identified in all cases during the surgery. The side-to-side difference in anterior knee laxity, pivot shift test, Lysholm knee score, the International Knee Documentation Committee (IKDC) subjective form, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were evaluated one year after the surgery. A second CT examination was performed 6-12 months after the surgery, if a posterior wall blowout-like phenomenon was identified in the first CT examination., Results: Two weeks after the surgery, 16 of the 105 patients showed a posterior wall blowout-like phenomenon. Twelve of the 16 cases demonstrated a regenerated posterior femoral cortex of the femoral bone tunnel on their second CT images. There were no significant differences between the posterior wall blowout-like phenomenon group and the normal posterior wall group in terms of a side-to-side difference in anterior knee laxity (0.4 ± 1.5 mm and 0.1 ± 1.6 mm, respectively), pivot shift test, Lysholm knee score, IKDC score, and KOOS at one year after surgery. The length and diameter of the femoral bone tunnel were not significantly different between the two groups., Conclusions: Posterior wall blowout-like phenomenon after ACL reconstruction using a cortical suspension device did not negatively influence clinical outcomes., Level of Evidence: III - retrospective comparative clinical study., Competing Interests: Declaration of competing interest The authors declare there are no conflicts of interest directly relevant to the content of this study., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: An increase in medial meniscus extrusion (MME) due to abnormal biomechanical stress leads to knee osteoarthritis (OA) progression. MME evaluation during walking is a key method of detecting dynamic changes in the meniscus, and in combination with motion analysis, can provide a deeper understanding of the mechanisms involved in the increase of MME., Objective: To validate the feasibility of MME dynamic evaluation in combination with a motion analysis system based on the correlation between the increase in MME and biomechanical factors., Methods: Twenty-three knees from 23 patients with mild to moderate knee OA were analysed in this study. The medial meniscus during walking was evaluated by ultrasound. The increase in MME was calculated as the difference between the minimum and maximum MME during walking. A three-dimensional motion analysis system was synchronised with the ultrasound and then, biomechanical factors such as knee moment and ground reaction force were evaluated., Results: The wave patterns of the mediolateral and vertical components of ground reaction forces and knee adduction moment were similar to those in the MME based on a high cross-correlation coefficient (>0.8). The increase in MME was significantly correlated with the peak value of the knee adduction moment (r = 0.54, P = 0.0073) but not with the mediolateral and vertical components of the ground reaction force., Conclusion: The findings show that knee adduction moment is correlated with an increase in MME during walking and indicates the validity and feasibility of the dynamic evaluation of MME in combination with a motion analysis system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Knee joint distraction (KJD) has received much attention as a joint preserving surgery, especially in young patients with advanced knee osteoarthritis (OA)., Methods: This study included 16 patients with advanced knee OA who underwent KJD combined with marrow stimulating techniques and were followed up for more than 2 years. The patients' clinical scores, including the Japanese Orthopaedic Association (JOA) score, Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, ROM, joint space width, and semiquantitative MRI were evaluated. The factors affecting clinical outcomes were analyzed., Results: Postoperatively, the JOA score and the individual scores of the KOOS subscales improved significantly (JOA score: P = 0.0028, KOOS-symptoms: P = 0.0016, -pain: P = 0.0011, -ADL: P = 0.0009, -sports/recreation: P = 0.0144, and -QOL: P = 0.0034). Although the extension of the knee joint did not change throughout the follow-up period, flexion of the joint deteriorated at the time of device removal but recovered to the preoperative level at the final follow-up. Preoperative joint space width was 2.4 ± 2.0 mm and at the final follow-up, it increased to 3.3 ± 1.5 mm, showing statistically significant improvement (P = 0.034). The postoperative semiquantitative MRI score also improved significantly (from 6.0 ± 3.0 to 42.1 ± 28.7, P = 0.0001). A high BMI was associated with a poor clinical outcome., Conclusion: Although the effect of marrow stimulating techniques for cartilage repair was not well clarified and the complication rate was high, the clinical and radiographic outcomes showed significant improvement after KJD combined with marrow stimulating techniques in patients with advanced knee OA. However, we should be careful about suggesting this procedure in obese patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Medial meniscus extrusion (MME) leads to symptomatic knee osteoarthritis (OA) due to increased mechanical stress. MME increases with weight-bearing, and the difference in MME between non-weight-bearing and weight-bearing status (ΔMME) is a factor that causes greater MME. The lateral wedge insole (LWI) is an ideal approach for decreasing the amount of ΔMME associated with the reduction of medial loading stress in the early stage of knee OA. However, the effect of the LWI for 3 months on the ΔMME and its response to OA stage have not been elucidated., Objective: To investigate the effects of the LWI for 3 months on MME and the ΔMME in each stage of OA., Methods: Participants were divided into three groups: no intervention with the LWI (control group; n = 9) and intervention with the LWI in early OA (early OA group: Kellgren-Lawrence (K/L) stage = 2, n = 17) and late OA (late OA group: K/L stage > 2, n = 13). MME was evaluated using ultrasound, and the ΔMME was obtained as the difference in MME from non-weight-bearing and weight-bearing conditions. These measurements were performed at two time points: the initial office visit as a baseline and post-3 months., Results: The weight-bearing MME and ΔMME values post-3 months were significantly decreased compared with those at baseline in the early OA group but not in the control or late OA groups., Conclusions: The use of the LWI for 3 months decreased weight-bearing MME and ΔMME values, and its effectiveness was more pronounced in the early stage of knee OA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Osteoarthritis (OA) is a progressive joint disorder, with abnormal remodeling of subchondral bone linked to the disruption of cartilage metabolism. Nerves also play an important role in bone remodeling in OA progression, and vasoactive intestinal peptide (VIP), one of the neuropeptides, plays an important role in bone metabolism. The aim of this study was to analyze the expression pattern of VIP in subchondral bone, and its potential as a therapeutic target for OA progression., Design: The pattern of VIP expression in the human tibia was histologically evaluated. The effect of VIP on angiogenesis was investigated using human umbilical vein endothelial cells (HUVECs). Knee OA was induced by the resection of the medial meniscotibial ligament in C57BL/6 mice. A VIP receptor antagonist was intraperitoneally administered postoperatively, and therapeutic effects were analyzed at 4 and 8 weeks., Results: VIP expression in the subchondral bone increased as OA progressed in human tibia. VIP was also expressed in the vascular channels into the cartilage layer. The total length and branch points were significantly increased, due to the VIP receptor agonist in HUVECs. In OA mice, the VIP receptor antagonist could prevent cartilage degeneration and subchondral bone sclerosis. The Osteoarthritis Research Society International score in the VIP receptor antagonist group was significantly lower than in the control group., Conclusion: VIP is involved in the progression of OA through its effect on subchondral bone sclerosis and angiogenesis. Inhibition of VIP signaling has the potential to be a therapeutic target to prevent OA progression., Competing Interests: Declaration of Competing Interest The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Medial meniscal extrusion (MME) is a risk factor for the progression of knee osteoarthritis (OA). MME evaluation is crucial and it is commonly performed using magnetic resonance imaging (MRI) or static ultrasonography. We developed a prototype flat-shaped ultrasound transducer to visualize the actual meniscal movements during walking., Objective: The aim of this study was to investigate whether it is feasible to visualize and evaluate the meniscal movements during walking using the novel flat-shaped ultrasound transducer for dynamic ultrasonography., Methods: Six participants who were diagnosed with primary unilateral or bilateral tibiofemoral knee OA on radiography (mean age, 67.1 ± 9.9 years; males/females, 4/2) and six healthy volunteers without any symptoms in their knees (mean age, 26.3 ± 4.0 years; males/females, 4/2) were enrolled in this study. The movement of the medial meniscus during walking was visualized using the novel transducer and the gait motion was recorded as video images that were synchronized with the ultrasonogram. MME and ΔMME (the difference between the minimum and maximum MME during the stance phase of the gait cycle) were evaluated in those with OA and compared with those in healthy volunteers., Results: In both groups, MME was visualized clearly in the stance phase. The mean values of MME and ΔMME in the knee OA group were significantly greater than those in the control group (P < .01)., Conclusions: Dynamic meniscal movement during gait can be evaluated with the specially developed novel ultrasound transducer. Our approach will be helpful in unveiling unknown pathological mechanisms in knee OA., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property. We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address that is accessible by the Corresponding Author., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Lateral thrust is known to be risk factors for knee osteoarthritis progression. Medial meniscus extrusion is also known to be risk factors for knee osteoarthritis progression; moreover, the amount of change in medial meniscus extrusion from non-weight bearing to weight bearing is an important factor for the progression of knee osteoarthritis. This study aimed to investigate the correlation between lateral thrust and the change in medial meniscus extrusion., Methods: In total, 44 knees from 44 patients (mean age, 68.9 years) with knee osteoarthritis were divided into two groups according to the Kellgren-Lawrence grade: early-stage osteoarthritis (Kellgren-Lawrence = 2) and severe osteoarthritis (Kellgren-Lawrence = 3 or 4). The lateral thrust during gait, represented as the lateral acceleration peak immediately after heel strike, was recorded by an inertial sensor. The amount of change in medial meniscus extrusion, which was the difference between weight-bearing (unipedal standing) and non-weight-bearing (supine) conditions, was evaluated using ultrasonography., Results: The mean value of the lateral acceleration peak in the severe osteoarthritis group was higher than that of the early-stage osteoarthritis group (p < 0.05). The non-weight-bearing and weight-bearing medial meniscus extrusion in the severe OA group were significantly higher than those of the early-stage osteoarthritis group (p < 0.001). However, the amount of change in medial meniscus extrusion in severe osteoarthritis group was significantly lower than in the early-stage osteoarthritis group (p < 0.05). The amount of change in medial meniscus extrusion showed a significant correlation with the lateral acceleration peak in the early-stage osteoarthritis group (r = 0.56, p < 0.001). On the other hand, there was no significant correlation in the severe osteoarthritis group., Conclusion: The lateral thrust shows a positive correlation with the amount of change in medial meniscus extrusion by weight bearing in patients with early-stage knee osteoarthritis., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Large differences in tibial tubercle-posterior cruciate ligament (TT-PCL) distance were described in several reports between countries, suggesting that abnormal TT-PCL distance is variable due to individual patient size. This study aimed to clarify the relationship between TT-PCL distance and patient size, and to determine a method for describing individualized TT lateralization., Methods: We analyzed 41 patients with recurrent patellar dislocation (RPD) and 41 age-matched patients without patellar instability who underwent primary anterior cruciate ligament reconstruction (control). TT-PCL distance and tibia width (TW) were measured based on preoperative T2-weighted magnetic resonance imaging. Then, TT-PCL distance was standardized based on TW (TT-PCL ratio), and TT-PCL distance and ratio were compared between groups. Correlations were investigated among TT-PCL distance, TT-PCL ratio and each measurement (patient height, weight, TW)., Results: Strong positive correlations were observed between TW and patient height, and weak or moderate positive correlations were found between TT-PCL distance and each parameter. The mean TT-PCL distance was 21.2 and 20.6 mm (P = .39), while the mean TT-PCL ratio was 31.6% and 29.0% (P = .0093) in the RPD and control groups, respectively. The TT-PCL ratio was <34% in 39 of 41 knees (95.1%) in the control group. No correlation was indicated between the TT-PCL ratio and patient size., Conclusions: Our findings demonstrate that the TT-PCL ratio is not affected by patient size, although the TT-PCL distance is associated with knee size and patient height. The TT-PCL ratio could be an important index for identifying patients for whom distal realignment surgery should be considered., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Patients with discoid lateral meniscus (DLM) are prone to meniscal injuries related to its shape and abnormal mobility. The anatomical joint inclination of the proximal tibiofibular joint (PTFJ) can also affect joint movement in knee motion. However, an association between PTFJ morphology and DLM remains unclear. The purpose of this study was to investigate the morphology of the PTFJ on MRI and how this differs between patients with and without DLM., Materials and Methods: Fifty-eight patients with DLM and 58 age-matched controls (normal meniscus) were included in this study. Slices from preoperative MRI sagittal images that clearly showed the PTFJ were used for measurements. The angle between the PTFJ and the perpendicular line of the fibula axis was measured as the inclination angle, and patients were classified as horizontal-type (<20°) or oblique-type (>20°). The inclination angle was also compared among patients with open and closed epiphysis in both groups to assess the effect of age., Results: Patients in the horizontal-type PTFJ group frequently had DLM. Before epiphyseal closure, most patients had a horizontal-type PTFJ, with or without DLM. However, in older patients with a closed epiphysis, most with a normal meniscus had an oblique-type PTFJ, and those with DLM retained the horizontal-type joint., Conclusion: The horizontal-type PTFJ was significantly associated with DLM, and patients with DLM tended to retain a horizontal-type PTFJ after epiphyseal closure. In contrast, in patients with a normal meniscus, the PTFJ may change from a horizontal-type to an oblique-type PTFJ in line with bone maturity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ankle arthroscopy is a minimally invasive technique for ankle joint treatment. However, injury to the intermediate dorsal cutaneous nerve (IDCN) and the medial dorsal cutaneous nerve (MDCN) is a common complication during anterior portal placement. To prevent injuries, methods such as palpating the nerves topographically and marking the nerves by transilluminating the skin with an arthroscope have been proposed. Easier and more definitive methods of identifying the IDCN and MDCN should result in a reduction of complications. Recently, a vein imaging system was developed that projects images of subcutaneous vasculature directly onto the skin with the use of near-infrared (NIR) light. Because anatomic studies have shown that superficial veins accompany the IDCN and MDCN, protecting the subcutaneous veins could lower the risk of nerve injury. We introduce our technique for the creation of an ankle arthroscopic portal using an NIR imaging system, which displays the vein image on the skin, to prevent injury to the superficial veins and, consequently, reduce IDCN and MDCN injuries. This is the first technical report on the prevention of vein and nerve injuries using an NIR imaging system. Our technique for avoiding vein injury using a peripheral vein illumination device during anterior portal placement in ankle arthroscopy could lower the risk of complications.

Background: It is known that a lateral wedge insole (LWI) decreases medial loading stress in the knee. Medial meniscus pathology, such as a degenerative tear or a root tear, leading to malfunction and medial meniscus extrusion (MME), is a critical condition that leads to severe osteoarthritis (OA). However, the effect of LWI on MME is still unknown. The objective of this study was to investigate the effect of LWI use on MME in knee OA using ultrasonography., Methods: Thirty-one knees from 18 patients with knee OA diagnosed radiographically were allocated to the OA group (mean age, 73.6years; sex M:F, 2:16). Twenty-two knees from 11 volunteers without knee OA were also enrolled as an age-matched control group. MME was evaluated using ultrasonography with the patients in three positions: supine, standing without LWI, and standing with LWI., Results: In both groups, the mean values of the MME increased significantly when patients were in the standing position compared to the supine position. In the OA group, MME significantly decreased with LWI use. There was no significant difference in MME between use and non-use of an LWI in the control group., Conclusions: The LWI could significantly decrease MME in patients with knee OA., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: A high incidence of dorsomedial cutaneous nerve (DMCN) damage in hallux valgus surgery has been reported. Identification of the vein around 1st metatarsal head is reported to be helpful to reduce the DMCN damage during surgery. The near-infrared (NIR) vascular imaging system, the VeinViewer ® Flex, projects the vein onto the skin. The purpose of this study was to investigate the difference of the vein course between normal and hallux valgus foot using the VeinViewer ® Flex, and to validate that the DMCN was accompanied with its vein., Methods: Twenty-seven feet with the hallux valgus and 27 feet in healthy subjects were included. The vein was projected onto the skin at the metatarsal head by the VeinViewer ® Flex. The distance between the vein and the mid-line of the metatarsal head was measured. The correlation of the distance and hallux valgus angle or 1-2 intermetatarsal angle (IMA) was analyzed. The vein depicted by the VeinViewer ® Flex and operative findings was compared in 4 patients during surgery., Results: The vein in the hallux valgus patients shifted toward the dorsolateral side on the metatarsal bone head compared to that in healthy subjects. The distance from the midline of the 1st metatarsal bone to the vein in the hallux valgus (12.1 mm) was significantly higher than that in healthy subjects (2.7 mm) (p < 0.05). There was a significant correlation between the shift of the vein course toward dorsolateral and IMA. Surgical exploration revealed that the vein depicted by VeinViewer ® Flex could be easily identified and the nerve was along with this vein in all 4 surgical cases., Conclusions: The vein in the hallux valgus patients shifted toward the dorsolateral on the metatarsal bone and it could be a landmark to identify DMCN. The NIR vascular imaging system would be useful to reduce the risk of nerve damage in great toe surgery., (Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to evaluate bone tunnel changes following anterior cruciate ligament (ACL) reconstruction during the early postoperative period using computed tomography (CT), and to understand the impact of postoperative immobilization on these changes., Methods: Twenty patients who underwent double-bundle ACL reconstruction using hamstring tendon autografts were included. We subcategorized patients into two groups: patients who underwent isolated ACL reconstruction and had three days of knee immobilization (Group A, n=10); and patients with concomitant meniscus injuries who underwent ACL reconstruction and meniscus repair simultaneously (Group B, n=10) had their knees immobilized for two weeks after surgery. Bone tunnel enlargement was evaluated using CT imaging at one to three days, two weeks, one month, three months and six months after surgery. The cross-sectional area of the femoral and tibial tunnels was measured, and enlargement rate was calculated. The tunnel center location at two weeks after surgery was also evaluated., Results: The mean cross-sectional area adjacent to the joint space of the femoral and tibial tunnels significantly increased immediately after surgery, especially in the first month (P<0.01). However, after one to six months they were not increased (P>0.01). There was no significant difference in tunnel enlargement rate between group A and B. Tunnel center location changed even in the first two weeks., Conclusions: Bone tunnel enlargement following double-bundle ACL reconstruction occurred at an earlier time point after surgery than anticipated. Postoperative immobilization could not prevent bone tunnel enlargement, but might prevent tunnel migration., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: A symptomatic bipartite patella is rarely seen in athletic adolescents or young adults in daily clinical practice. To date, only a limited number of studies have focused on patellofemoral alignment. The current study revealed a unique patellofemoral alignment in a patient with a symptomatic bipartite patella., Methods: Twelve patients with 12 symptomatic bipartite patellae who underwent arthroscopic vastus lateralis release (VLR) were investigated (10 males and two females, age: 15.7±4.4years). The radiographic data of contralateral intact and affected knees were reviewed retrospectively. From the lateral- and skyline-view imaging, the following parameters were measured: the congruence angle (CA), the lateral patellofemoral angle (LPA), and the Caton-Deschamps index (CDI). As an additional parameter, the bipartite fragment angle (BFA) was evaluated against the main part of the patella in the skyline view., Results: Compared with the contralateral side, the affected patellae were significantly medialized and laterally tilted (CA: P=0.019; LPA: P=0.016), although there was no significant difference in CDI (P=0.877). This patellar malalignment was found to significantly change after VLR (CA: P=0.001; LPA: P=0.003) and the patellar height was significantly lower than in the preoperative condition (P=0.016). In addition, the BFA significantly shifted to a higher degree after operation (P=0.001)., Conclusions: Patients with symptomatic bipartite patellae presented significantly medialized and laterally tilted patellae compared with the contralateral intact side. This malalignment was corrected by VLR, and the alignment of the bipartite fragment was also significantly changed., Level of Evidence: Level IV, case series., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background Aims: The therapeutic application of CD34+ circulating progenitor cells (which includes endothelial progenitor cells) has been hampered by the quantity and quality of isolated circulating CD34(+) cells from the patient's peripheral blood. Our group had previously established a suspension culture system for human CD34(+) cells, with increased quantity and quality (QQ) of the angiogenic cell product. We successfully scaled up the expansion process with the use of culture bags because there is the need to move toward a dynamic and fully controlled bioreactor system to meet Good Manufacturing Practice (GMP) standards and attain clinically meaningful cell doses in a time- and cost-effective way., Methods: CD34(+) cells isolated from mobilized peripheral blood of healthy donors were expanded ex vivo for 7 days in QQ medium (serum-free) in cell culture bags (30 mL) and pre- and post-expansion cells were characterized by means of flow cytometry and quantitative polymerase chain reaction; angiogenic potential was assessed by use of the in vitro tube formation assay., Results: Our data show effective expansion of the cultured population (7-fold) while maintaining the stem/progenitor content and increasing the endothelial population. Moreover, post-expanded cells showed higher tube formation capacity compared with pre-expanded cells. In addition, an upregulation of the anti-inflammatory gene expression and a downregulation of pro-inflammatory genes were observed, which suggests that the increase in angiogenic potential is not paired with an increase in the inflammatory profile., Conclusions: The QQ expansion method was successfully scaled up to cell culture bags and was able to meet GMP standards, with a higher in vitro angiogenic profile., (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Human blood-derived CD133(+) cell populations, which are believed to represent a hematopoietic/endothelial progenitor fraction, have the ability to promote the repair of injured spinal cord in animal models. However, the mechanisms by which CD133(+) cell transplantation promotes spinal cord regeneration remain to be clarified. Another possible hurdle on the way to clinical applicability of these cells is their scarce representation in the overall population of mononuclear cells. We therefore analyzed and compared ex-vivo expanded human cord blood derived CD133(+) cells with freshly isolated CD133(+) cells as well as corresponding CD133(-) control mononuclear cells in respect to their ability to promote spinal cord repair using in vitro assays and cell transplantation into a mouse spinal cord injury model. In vitro, expanded cells as well as fresh CD133(+) cells formed endothelial progenitor cell (EPC) colonies, whereas CD133(-) cells formed no EPC colonies. In vivo, the administration of fresh CD133(+) and expanded cells enhanced angiogenesis, astrogliosis, axon growth and functional recovery after injury. In contrast, the administration of CD133(-) cells failed to promote axon growth and functional recovery, but moderately enhanced angiogenesis and astrogliosis. In addition, high-dose administration of expanded cells was highly effective in the induction of regenerative processes at the injured spinal cord., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Cardiovascular disease is the leading cause of death and disability in the Western world. In addition to the advancement of current therapeutic approaches to reduce the associated morbidity and mortality, regenerative medicine and cell-based therapy have been areas of continuous investigation. Circulating and bone-marrow-derived stem or endothelial progenitor cells are an attractive source for regenerative therapy in the cardiovascular field. In this review, we highlight the advantages and limitations of this approach with a focus on key observations from animal studies and clinical trials., (Copyright 2010 Mosby, Inc. All rights reserved.)

Background: This study was performed to evaluate whether the radiographic crossover sign influences the painful femoroacetabular impingement or the radiographic progression of osteoarthritis after rotational acetabular osteotomy (RAO)., Methods: A total of 104 patients (115 hips) with preosteoarthritis (pre-OA) or early-stage OA of the hip due to dysplasia underwent RAO. Their mean age at the time of surgery was 34.7 years. The mean follow-up period was 13 years. Clinical follow-up was performed with the system of Merle d'Aubigne, and the impingement sign was evaluated. Radiographic analyses included the center-edge angle, acetabular roof angle, head lateralization index (HLI), joint congruency, crossover sign, posterior wall sign, acetabular index of depth to width, pistol grip deformity, and femoral head/femoral neck ratio., Results: The mean clinical score improved significantly from 14.6 preoperatively to 17.0 at follow-up. The impingement sign at follow-up was observed in 14 hips (12.2%). The center-edge angle, acetabular roof angle, and head lateralization index (HLI) improved significantly after surgery. The crossover sign was observed in 8 hips (7.0%) preoperatively and in 49 hips (42.6%) postoperatively. The posterior wall sign was observed in 70 hips (60.9%) preoperatively and in 73 hips (63.5%) postoperatively. The impingement sign after RAO was positive significantly in the postoperative crossover sign-positive hips. Radiographic progression of OA was observed in 11 hips (crossover sign was positive in 7 hips and negative in 4 hips). The only factors significantly associated with radiographic progression after RAO were fair postoperative joint congruency and age at surgery., Conclusions: Although there was no significant radiographic progression of OA despite significant retroversion, anterior impingement and radiographic crossover sign after RAO are should be checked during the procedure. The goal of RAO should be correct alignment of the acetabulum including a correct version with a negative crossover sign.

Background Aims: The distinction between hematopoietic stem cells (HSC) and endothelial progenitor cells (EPC) is poorly defined. Co-expression of CD34 antigen with vascular endothelial growth factor (VEGF) receptor (VEGFR2) is currently used to define EPC ( 1 )., Methods: We evaluated the phenotypic and genomic characteristics of peripheral blood-derived CD34(+) cells in 22 granulocyte-colony-stimulating factor (G-CSF)-mobilized patients with severe coronary artery disease and assessed the influence of cell selection and storage on CD34(+) cell characteristics., Results: The median CD34(+) cell contents in the products before and after enrichment with the Isolex 300i Magnetic Cell Selection System were 0.2% and 82.5%, respectively. Cell-cycle analysis showed that 80% of CD34(+) cells were in G0 stage; 70% of the isolated CD34(+) cells co-expressed CD133, a marker for more immature progenitors. However, less than 5% of the isolated CD34(+) cells co-expressed the notch receptor Jagged-1 (CD339) and only 2% of the isolated CD34(+) population were positive for VEGFR2 (CD309). Molecular assessment of the isolated CD34(+) cells demonstrated extremely low expression of VEGFR2 and endothelial nitric oxide synthase (eNOS) and high expression of VEGF-A. Overnight storage at 4 degrees C did not significantly affect CD34(+) cell counts and viability. Storage in liquid nitrogen for 7 weeks did not affect the percentage of CD34(+) cells but was associated with a 26% drop in cell viability., Conclusions: We have demonstrated that the majority of isolated CD34(+) cells consist of immature and quiescent cells that lack prototypic markers of EPC. High VEGF-A gene expression might be one of the mechanisms for CD34(+) cell-induced angiogenesis.

The aim of the present study was to clarify the morphologic characteristics of time-intensity curves (TICs) that are useful for distinguishing benign from malignant lesions. One hundred three patients with breast lesions underwent dynamic breast MRI. The areas under the receiver operating characteristic (ROC) curves (AUC) from every component of TIC were compared between benign and malignant disease. As a result, angle of cross line between 1 and 4 min is more useful than rapid enhancement for distinguishing benign from malignant lesions.

Failures in fracture healing are mainly caused by a lack of vascularization. Adult human circulating CD34+ cells, an endothelial/hematopoietic progenitor-enriched cell population, have been reported to differentiate into osteoblasts in vitro; however, the therapeutic potential of CD34+ cells for fracture healing is still unclear. Therefore, we performed a series of experiments to test our hypothesis that functional fracture healing is supported by vasculogenesis and osteogenesis via regenerative plasticity of CD34+ cells. Peripheral blood CD34+ cells, isolated from total mononuclear cells of adult human volunteers, showed gene expression of osteocalcin in 4 of 20 freshly isolated cells by single cell reverse transcriptase-polymerase chain reaction analysis. Phosphate-buffered saline, mononuclear cells, or CD34+ cells were intravenously transplanted after producing nonhealing femoral fractures in nude rats. Reverse transcriptase-polymerase chain reaction and immunohistochemical staining at the peri-fracture site demonstrated molecular and histological expression of human-specific markers for endothelial cells and osteoblasts at week 2. Functional bone healing assessed by biomechanical as well as radiological and histological examinations was significantly enhanced by CD34+ cell transplantation compared with the other groups. Our data suggest circulating human CD34+ cells have therapeutic potential to promote an environment conducive to neovascularization and osteogenesis in damaged skeletal tissue, allowing the complete healing of fractures.