Keiji Tensho

Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months.

Among autologous somatic stem cells, bone marrow‐derived mesenchymal stem cells (BMSCs) are the most widely used worldwide to repair not only mesenchymal tissues (bone, cartilage) but also many other kinds of tissues, including heart, skin, and liver. Autologous BMSCs are thought to be safe because of the absence of immunological reaction and disease transmission. However, it is possible that they will form tumours during long‐term follow‐up. In 1988, we transplanted autologous BMSCs to repair articular cartilage, which was the first such trial ever reported. Subsequently we performed this procedure in about 40 patients. Demonstration that neither partial infections nor tumours appeared in these patients provided strong evidence for the safety of autologous BMSC transplantation. Thus, in this study we checked these patients for tumour development and infections. Between January 1998 and November 2008, 41 patients received 45 transplantations. We checked their records until their last visit. We telephoned or mailed the patients who had not visited the clinics recently to establish whether there were any abnormalities in the operated joints. Neither tumours nor infections were observed between 5 and 137 (mean 75) months of follow‐up. Autologous BMSC transplantation is a safe procedure and will be widely used around the world. Copyright

Xeno-free proliferation of human bone marrow mesenchymal stem cells

The proliferation of human bone marrow mesenchymal stem cells (MSCs) employing xeno-free materials not containing fetal calf serum (FCS) and porcine trypsin was investigated for the regenerative medicine of cartilage using MSCs. Four sequential subcultivations of MSCs using a medium containing 10% FCS and recombinant trypsin (TrypLESelect™) resulted in cell growth comparable to that with porcine trypsin. There was no apparent difference in the cell growth and morphology between two kinds of MSC stored in liquid nitrogen using 10% FCS plus DMSO or serum-free TC protector™. MSCs were isolated from human bone marrow cells, stored in liquid nitrogen, and sequentially subcultivated four times employing conventional materials that included FCS, porcine trypsin, and DMSO, or xeno-free materials that included serum-free medium (MesenCult-XF™), TC protector™ and TrypLESelect™. Cells in the culture using the xeno-free materials maintained typical fibroblast-like morphology and grew more rapidly than the cells in the culture using the conventional materials, while the cell surface markers of MSCs (CD90 and CD166) were well maintained in both cultures. Chondrogenic pellet cultures were carried out using these subcultivated cells and a medium containing TGFβ3 and IGF1. The pellet culture using cells grown with the xeno-free materials showed an apparently higher gene expression of aggrecan, a chondrocyte marker, than the pellet culture using cells grown with the conventional materials. Consequently, MSCs that are isolated, stored, and grown using the xeno-free materials including the serum-free medium (MesenCult-XF™), TC protector™, and recombinant trypsin (TrypLESelect™) might be applicable for regenerative medicine of cartilage.

Bony Landmarks of the Anterior Cruciate Ligament Tibial Footprint A Detailed Analysis Comparing 3-Dimensional Computed Tomography Images to Visual and Histological Evaluations

Background: Although the importance of tibial tunnel position for achieving stability after anterior cruciate ligament (ACL) reconstruction was recently recognized, there are fewer detailed reports of the anatomy of the tibial topographic footprint compared with the femoral side. Hypothesis: The ACL tibial footprint has a relationship to bony prominences and surrounding bony landmarks. Study Design: Descriptive laboratory study. Methods: This study consisted of 2 anatomic procedures for the identification of bony prominences that correspond to the ACL tibial footprint and 3 surrounding landmarks: the anterior ridge, lateral groove, and intertubercular fossa. In the first procedure, after computed tomography (CT) was performed on 12 paired, embalmed cadaveric knees, 12 knees were visually observed, while their contralateral knees were histologically observed. Comparisons were made between macroscopic and microscopic findings and 3-dimensional (3D) CT images of these bony landmarks. In the second procedure, the shape of the bony prominence and incidence of their bony landmarks were evaluated from the preoperative CT data of 60 knee joints. Results: In the first procedure, we were able to confirm a bony prominence and all 3 surrounding landmarks by CT in all cases. Visual evaluation confirmed a small bony eminence at the anterior boundary of the ACL. The lateral groove was not confirmed macroscopically. The ACL was not attached to the lateral intercondylar tubercle, ACL tibial ridge, and intertubercular space at the posterior boundary. Histological evaluation confirmed that the anterior ridge and lateral groove were positioned at the anterior and lateral boundaries, respectively. There was no ligament tissue on the intercondylar space corresponding to the intercondylar fossa. In the second investigation, the bony prominence showed 2 morphological patterns: an oval type (58.3%) and a triangular type (41.6%). The 3 bony landmarks, including the anterior ridge, lateral groove, and intertubercular fossa, existed in 96.6%, 100.0%, and 96.6% of the cases, respectively. Conclusion: There is a bony prominence corresponding to the ACL footprint and bony landmarks on the anterior, posterior, and lateral boundaries. Clinical Relevance: The study results may help create an accurate and reproducible tunnel, which is essential for successful ACL reconstruction surgery.

The effects of heat on the biological activity of recombinant human bone morphogenetic protein-2

This study was designed to investigate effects of heat on the bone-inducing activity of recombinant human bone morphogenetic protein (rhBMP)-2. rhBMP-2 samples were heated at 50, 70, 90, or 100°C for 15 min, or 1, 2, 4, or 8 h, or autoclaved at 120°C for 15 min. The bone-inducing activity of the rhBMP-2 before and after heating was assayed in in vivo and in vitro systems. For the in vivo assay, 5 µg rhBMP-2 samples were impregnated into porous collagen disks (6 mm in diameter, 1 mm thickness), freeze dried, and implanted into the back muscles of ddY mice. Three weeks later, the implant was harvested from the host and examined for ectopic new bone tissue by radiography. The new bone mass was quantified by single-energy X-ray absorptiometry. The in vitro activity of the rhBMP-2 was assayed by adding the BMP sample at a concentration of 100 ng/ml to cultures of MC3T3-E1 cells. After 48 h, the alkaline phosphatase activity was measured. After heating at 50° or 70°C, no significant reduction in bone-inducing activity was noted in either in vivo or in vitro assay systems unless the protein was exposed to sustained heat at 70°C for 8 h, based on in vitro assay data. However, heating above 90°C and for longer periods led to a decrease in the biological activity of the rhBMP-2 in a time- and temperature-dependent manner. rhBMP-2 was rendered inactive when exposed to temperatures at or in excess of 120°C.

What Components Comprise the Measurement of the Tibial Tuberosity-Trochlear Groove Distance in a Patellar Dislocation Population?

BACKGROUND The tibial tuberosity-trochlear groove distance is used as an indicator for medial tibial tubercle transfer; however, to our knowledge, no studies have verified whether this distance is strongly affected by tubercle lateralization at the proximal part of the tibia. We hypothesized that the tibial tuberosity-trochlear groove distance is mainly affected by tibial tubercle lateralization at the proximal part of the tibia. METHODS Forty-four patients with a history of patellar dislocation and forty-four age and sex-matched controls were analyzed with use of computed tomography. The tibial tuberosity-trochlear groove distance, tibial tubercle lateralization, trochlear groove medialization, and knee rotation were measured and were compared between the patellar dislocation group and the control group. The association between the tibial tuberosity-trochlear groove distance and three other parameters was calculated with use of the Pearson correlation coefficient and partial correlation analysis. RESULTS There were significant differences in the tibial tuberosity-trochlear groove distance (p < 0.001) and knee rotation (p < 0.001), but there was no difference in the tibial tubercle lateralization (p = 0.13) and trochlear groove medialization (p = 0.08) between the patellar dislocation group and the control group. The tibial tuberosity-trochlear groove distance had no linear correlation with tubercle lateralization (r = 0.21) or groove medialization (r = -0.15); however, knee rotation had a good positive correlation in the patellar dislocation group (r = 0.62). After adjusting for the remaining parameters, knee rotation strongly correlated with the tibial tuberosity-trochlear groove distance (r = 0.69, p < 0.001), whereas tubercle lateralization showed moderate significant correlations in the patellar dislocation group (r = 0.42; p = 0.005). CONCLUSIONS Because the tibial tuberosity-trochlear groove distance is affected more by knee rotation than by tubercle malposition, its use as an indicator for tibial tubercle transfer may not be appropriate. CLINICAL RELEVANCE Surgical decisions of tibial tubercle transfer should be made after the careful analysis of several underlying factors of patellar dislocation.

Snapping pes syndrome after total knee arthroplasty

Snapping syndrome rarely occurs at the knee joint. This is the first report of snapping pes syndrome after total knee arthroplasty. Surgeons should be aware of the presence of such a case and pay attention to the fact that snapping symptoms could be caused by a residual bony prominence and a change in alignment after total knee arthroplasty. Level of evidence Therapeutic study, Case report with no comparison group, Level IV.

Hydroxyapatite Block for Reconstruction of Severe Dysplasia or Acetabular Bone Defects in Total Hip Arthroplasty: Operative Technique and Clinical Outcome

Fourteen hips in 14 patients (all female; average age, 64 years) with severe bone defects due to developmental dysplasia of the hip or migration of the socket were treated with hydroxyapatite block with impacted morselized bone graft in conjunction with a cemented socket. All patients were followed clinically in a prospective fashion, and radiographs were analyzed retrospectively. One initial patient had 17-year follow-up, whereas the remaining 13 patients had follow-up between 4 and 6.5 years. No acetabular components were revised, including the socket of a 17-year postoperative case that remains rigidly fixed and supported by the graft and hydroxyapatite block with only mild polyethylene wear and minor osteolysis. Osteointegration and good clinical outcome were achieved in all cases by reconstruction with this technique in total hip arthroplasty.

Blocking of tumor necrosis factor activity promotes natural repair of osteochondral defects in rabbit knee

Background and purpose Osteochondral defects have a limited capacity for repair. We therefore investigated the effects of tumor necrosis factor (TNF) signal blockade by etanercept (human recombinant soluble TNF receptor) on the repair of osteochondral defects in rabbit knees. Material and methods Osteochondral defects (5 mm in diameter) were created in the femoral patellar groove in rabbits. Soon after the procedure, a first subcutaneous injection of etanercept was performed. This single injection or, alternatively, 4 injections in total (twice a week for 2 weeks) were given. Each of these 2 groups was divided further into 3 subgroups: a low-dose group (0.05 μg/kg), an intermediate-dose group (0.4 μ g/kg), and a high-dose group (1.6 μ g /kg) with 19 rabbits in each. As a control, 19 rabbits were injected with water alone. The rabbits in each subgroup were killed 4 weeks (6 rabbits), 8 weeks (6 rabbits), or 24 weeks (7 rabbits) after surgery and repair was assessed histologically. Results Histological examination revealed that the natural process of repair of the osteochondral defects was promoted by 4 subcutaneous injections of intermediate-dose etanercept and by 1 or 4 injections of high-dose etanercept at the various time points examined postoperatively (4, 8, and 24 weeks). Western blot showed that rabbit TNFα had a high affinity for etanercept. Interpretation Blocking of TNF by etanercept enabled repair of osteochondral defects in rabbit knee. Anti-TNF therapy could be a strategy for the use of tissue engineering for bone and cartilage repair.

Standing Versus Supine Radiographs to Evaluate Femoral Head Penetration in the Polyethylene Liner After Total Hip Arthroplasty

The linear penetration rates for ceramic femoral heads on conventional and highly cross-linked polyethylene were measured and compared with radiographs taken in the standing and supine position taken three weeks postoperatively and at final follow-up. Seventy-five patients (83 hips) with conventional polyethylene (group-1) and two hundred and seventy five patients (300 hips) with highly cross-linked polyethylene (group-2) were studied. Follow-up periods were 14.5years in group-1 and 8.6years in group-2. The average penetration rates in group-1 were 0.17mm/year in supine position and 0.18mm/year in standing position (P<0.05). On the other hand, the rates in group-2 were 0.03mm/year and 0.04mm/year respectively (P<0.05). Although there were statistical differences between groups, 0.01mm differences are probably not clinically relevant.

Reconstruction of the Shallow Acetabulum With a Combination of Autologous Bulk and Impaction Bone Grafting Fixed by Cement

BackgroundAcetabular bone deficiency, especially proximal and lateral deficiency, is a difficult technical problem during primary total hip arthroplasty (THA) in developmental dysplasia of the hip (DDH). We report a new reconstruction method using a medial-reduced cemented socket and additional bulk bone in conjunction with impaction morselized bone grafting (additional bulk bone grafting method).Questions/purposesIn a population of patients with acetabular dysplasia undergoing THA using a medial-reduced cemented socket and additional bulk bone with impacted morselized bone grafting, we evaluated (1) the radiographic appearance of bone graft; (2) the proportion of cups that developed loosening and subsequent revision; and (3) clinical results (outcome scores and complications).MethodsForty percent of 330 THAs for DDH performed at one center between 1999 and 2009 were defined as shallow dysplastic hips. The additional bulk bone grafting method was performed on 102 THAs with shallow acetabulum (31% for DDH) at one center between 1999 and 2009. We used this approach and technique for shallow acetabuli when a cup protruded from the lateral acetabular edge in preoperative templating. The other 132 dysplastic hips without bone grafting had THA performed at the same periods and served as a control. Acetabuli were defined as shallow when the depth was less than or equal to one-fifth of the pelvic height (cranial-caudal length on radiograph). The additional bulk bone grafting technique was as follows: the resected femoral head was sectioned at 1 to 2 cm thickness, and a suitable size of the bulk bone graft was placed on the lateral iliac cortex and fixed by poly-l-lactate absorbable screws. Autologous impaction morselized bone grafting, with or without hydroxyapatite granules, was performed along with the implantation of a medial-reduced cemented socket. We defined an “incorporated” graft as remodeling and trabeculation including rounding off of the protruding edge of a graft beyond the socket. Radiographic criteria used for determining loosening were migration or a continuous radiolucent zone between the prosthesis/bone cement and host bone. Clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) and the Merle d’Aubigne and Postel score; complications were tallied from chart review. The followup was 10 ± 3 years (range, 6–15 years).ResultsOne acetabular component (1%) with severe shallow and steep acetabuli showed definite radiographic evidence of loosening and was revised. Clinically, the mean JOA score for the hips treated with additional bulk bone grafting THA in this study improved from 39 ± 10 points preoperatively to 95 ± 5 points postoperatively (p < 0.05, paired t-test). The mean Merle d’Aubigne and Postel score for the hips improved from 7 ± 2 points to 17 ± 1 points (p < 0.05, paired t-test). Complications included a Trendelenburg sign in one hip, dislocation in one, and transient partial sciatic nerve palsy in one. Within 3 years 6 months postoperatively, 101 of 102 additional bulk bone grafting cases showed successful bone remodeling and bone graft reorientation without collapse on radiographs. Partial resorption of the additional bone graft on the lateral side was observed in two hips (2%) with socket abduction angles of < 35°.ConclusionsAchieving stable acetabular fixation is often challenging in the dysplastic hip, especially shallow acetabulum, and a variety of techniques have been described. Early results of combining bulk graft with impaction of morselized graft are promising. Although each surgical technique was well established, further investigation for clinical results of a combination of these techniques might be necessary to confirm longer term outcomes.Level of EvidenceLevel IV, therapeutic study.