Comparison of recovery of mobility and self-efficacy after total knee arthroplasty based on two different protocols: A prospective cohort study.

Objectives: The purpose of this study was to compare the recovery of mobility and self-efficacy following total knee arthroplasty (TKA) between the 5-day and the 28-day protocol. This prospective cohort study was carried out at two hospitals.Methods: In total, 104 patients who underwent TKA were enrolled. The primary outcomes measured were Life Space Assessment (LSA) for mobility and modified-Gait Efficacy Scale (mGES) for self-efficacy. Knee Society Score (KSS) was used to estimate the functional outcomes. These assessments were performed in all patients preoperatively, and at 1, 3, and 6 months postoperatively. After calculating the propensity score using covariates, such as patient characteristics, LSA, mGES, and KSS at baseline, propensity score-adjusted multivariate analysis of covariance (MANCOVA) was performed.Results: MANCOVA revealed significant differences in LSA and mGES, but not in KSS, between the two protocols. The adjusted means of LSA and mGES in the 28-day protocol were significantly greater than those in the 5-day protocol in all the postoperative assessments.Conclusion: Mobility and self-efficacy were greater following the 28-day protocol than the 5-day protocol after TKA. Our findings suggest that the modified treatment procedure for improving mobility and self-efficacy is necessary to introduce the early discharge protocol in Japan.

Joint Arthroplasty With Osteochondral Grafting From the Knee for Posttraumatic or Degenerative Hand Joint Disorders.

PURPOSE: To describe the operative procedure and report the clinical outcomes of articular surface reconstruction for various hand joint disorders using autologous osteochondral grafts from the knee. METHODS: Ten patients underwent articular surface reconstruction for hand joint disorders with autologous osteochondral grafts from the patellofemoral joint. Mean patient age was 35 years (range, 15-52 y). The patients were followed for an average of 48 months (range, 16-89 mo). Arthroplasty was performed on the metacarpophalangeal joint in 4 cases, and on the proximal interphalangeal joint in 6 cases. The patients' clinical outcomes were evaluated with joint range of motion, visual analog scale (0-10 points), and Disabilities of the Arm, Shoulder, and Hand (DASH) score. Histological examination was performed in 3 cases after surgery. RESULTS: Graft union was confirmed in all cases without radiographic evidence of resorption or necrosis. Follow-up radiographic examinations showed good graft incorporation without signs of osteoarthritis such as joint space narrowing. The finger flexion-extension arc improved significantly from an average of 21° to 61°. The mean visual analog scale also improved significantly from 7.0 to 1.5. The mean total active motion showed a significant improvement from 151° before surgery to 201° after surgery, and the mean DASH score improved significantly from 33 to 12. There were no significant differences for the arc of finger motion and DASH score between metacarpophalangeal and proximal interphalangeal joint disorders or between hemiarthroplasty and total joint arthroplasty. Histological examination revealed viable chondrocytes in the implanted cartilage. CONCLUSIONS: Autologous osteochondral grafting from the patellofemoral joint provided satisfactory outcomes and may be a useful option for joint surface reconstruction of traumatic or degenerative hand joint disorders. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Improved quality of cartilage repair by bone marrow mesenchymal stem cells for treatment of an osteochondral defect in a cynomolgus macaque model.

BACKGROUND AND PURPOSE: Integration of repaired cartilage with surrounding native cartilage is a major challenge for successful tissue-engineering strategies of cartilage repair. We investigated whether incorporation of mesenchymal stem cells (MSCs) into the collagen scaffold improves integration and repair of cartilage defects in a cynomolgus macaque model. METHODS: Cynomolgus macaque bone marrow-derived MSCs were isolated and incorporated into type-I collagen gel. Full-thickness osteochondral defects (3 mm in diameter, 5 mm in depth) were created in the patellar groove of 36 knees of 18 macaques and were either left untreated (null group, n = 12), had collagen gel alone inserted (gel group, n = 12), or had collagen gel incorporating MSCs inserted (MSC group, n = 12). After 6, 12, and 24 weeks, the cartilage integration and tissue response were evaluated macroscopically and histologically (4 null, 4 gel, and 4 MSC knees at each time point). RESULTS: The gel group showed most cartilage-rich reparative tissue covering the defect, owing to formation of excessive cartilage extruding though the insufficient subchondral bone. Despite the fact that a lower amount of new cartilage was produced, the MSC group had better-quality cartilage with regular surface, seamless integration with neighboring naïve cartilage, and reconstruction of trabecular subchondral bone. INTERPRETATION: Even with intensive investigation, MSC-based cell therapy has not yet been established in experimental cartilage repair. Our model using cynomolgus macaques had optimized conditions, and the method using MSCs is superior to other experimental settings, allowing the possibility that the procedure might be introduced to future clinical practice.

Ultrasound-assisted closed reduction of distal radius fractures.

PURPOSE: To assess the accuracy and ability of ultrasound for monitoring closed reduction for distal radius fractures. METHODS: Consecutive patients undergoing ultrasound-guided closed reduction of acute, displaced distal radius fractures between January 2003 and December 2006 at our department were enrolled. The control group was extracted from patients who underwent a closed reduction for similar fractures under fluoroscopy or without any imaging assistance. To confirm the accuracy of the ultrasonography measurements, displacement distance values were compared with those on radiographic imaging before and after reduction. X-ray parameters for pre- and postreduction, reduction time, total cost, and success rate were compared between the ultrasound-guided and the control groups. RESULTS: The ultrasound-guided group consisted of 43 patients (mean age, 68 y) and the control group consisted of 57 patients, which included 35 patients (mean age, 74 y) with fluoroscopic reduction and of 22 patients (mean age, 72 y) with reduction unaided by imaging. There were no significant displacement differences between radiographic and ultrasound measurements. In x-ray parameters for pre- and postreduction, there were no significant differences between the 2 groups. Ultrasound-guided reduction took longer than the other 2 methods. The success rate of the ultrasound and the fluoroscopic groups were similar (95% and 94%, respectively). CONCLUSIONS: Our data suggest that ultrasound assistance can aid reduction of distal radius fractures as well as fluoroscopy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Acceptable parameters for alignment of distal radius fracture with conservative treatment in elderly patients.

BACKGROUND: There is a conflict in the treatment of distal radius fractures in elderly patients, because fracture reduction does not appear to be as strongly associated with functional outcomes as in younger patients. The purpose of this study was to evaluate radiographic findings of acceptable reduction without leading to wrist dysfunction and poor outcomes. METHODS: Fifty-two active and healthy elderly patients with conservatively managed distal radius fractures were included in the study. They consisted of 7 men and 45 women, all 60 years or older. Radiographic assessment included volar tilt, radial inclination and ulnar variance, and outcome evaluation included the Mayo wrist score and DASH score. As a control group, the preoperative radiographic and clinical outcomes were examined as well for 19 patients older than 60 with malunion, for whom corrective osteotomy was performed because of wrist dysfunction. The radiographic parameters and clinical outcomes were compared between the two groups in a statistical manner. Correlation coefficients of the radiographic parameters with Mayo wrist score and DASH score were analyzed by multiple regression. RESULTS: Volar tilt (mean -1.2°) and ulnar variance (mean 2.5 mm), as well as Mayo wrist score (mean 80.0 points) and DASH score (mean 8.6 points) in the objective group were significantly superior to those in the control group when comparing radiographic parameters and clinical outcomes. There was no significant difference between the two groups in regard to RI (mean 14.9°). Multiple regression analysis revealed that volar tilt and ulnar variance were significantly correlated with the clinical outcomes in the objective. CONCLUSION: The parameters of volar tilt and ulnar variance had a significant correlation with clinical outcomes. Clinical outcomes significantly worsened when those parameters exceeded a tolerable range. In elderly patients, it is important to determine an appropriate therapeutic modality for a distal radius fracture when considering the acceptable parameters for alignment.

Operative treatment of metacarpal and phalangeal fractures in athletes: early return to play.

BACKGROUND: Evaluating the outcomes of operative treatment for metacarpal and phalangeal fractures in athletes returning early to play and discussing the more effective methods that permit rapid early return to athletic activity. METHODS: We retrospectively identified a total of 105 metacarpal or phalangeal fractures in 105 athletes with conservative or operative treatment in our department. Of these, 20 athletes required an early return to sport because of a pending important game in their competition within 1 month after injury. Therefore, they underwent surgical treatment with open reduction and internal fixation of metacarpal or phalangeal fractures in an attempt to achieve an early return to their chosen sport at their usual competitive level. The patients included 6 rugby football players, 2 soccer goalkeepers, 3 American football players, 3 handball players, 2 baseball players and 4 who participated in other sports. The clinical records of preoperative and postoperative radiographs were available for all patients, and clinical outcome was evaluated by total active motion (TAM). RESULTS: The patients were followed up for a mean of 27 (24-43) months. At the latest follow-up examination, bone union was obtained in all cases. In cases with metacarpal and phalangeal fractures, the average TAM was 263° (range 240°-270°). CONCLUSION: We consider that an early comeback to training and competition can be permitted exclusively for patients with metacarpal and phalangeal fractures. It is important for the attending physician to administer such treatment after obtaining informed consent and develop a trusting relationship with the patient and other related individuals while paying attention to their hope of quick recovery.

Comparison of repair between cartilage and osteocartilage defects in rabbits using similarly manipulated scaffold-free cartilage-like constructs.

BACKGROUND: Articular cartilage has a limited capacity for spontaneous repair, and its repair remains a clinical challenge. The purpose of this study was to prepare scaffold-free cartilage-like constructs and evaluate the feasibility of their use for the treatment of cartilage and osteocartilage defects in vivo. METHODS: The scaffold-free constructs were prepared by chondrocytes isolated from the articular cartilage of rabbits using a high-density three-dimensional culture system. Two different defects, i.e., a chondral defect without oozing blood and an osteochondral defect with oozing blood, of 4-mm diameter, were created on the patellar groove of rabbits and forwarded to in vivo trials. In each defect, the constructs cut into 4-mm-diameter cylinders were grafted at the bottom of the defects. As a control, defects were only made on the contralateral knee joint in each rabbit. At 2, 4, 8 and 12 weeks after surgery, six rabbits in each group were evaluated macroscopically and histologically. RESULTS: In vitro, histological examination revealed that the constructs have the character of hyaline cartilage with a potential adhesiveness to surrounding tissue. In vivo, in two control groups, incomplete spontaneous cartilage repair was observed in the osteochondral defects, whereas no repair was observed in the chondral defects. In the two treated groups, the surviving constructs in chondral defects showed significantly better repair compared to those in osteochondral defects. CONCLUSIONS: It is possible for a chondral defect to be repaired by scaffold-free constructs in certain conditions. Establishing the optimal environment suitable for cartilage repair is warranted.

A simple method for choosing treatment of distal radius fractures.

PURPOSE: To design an easy-to-use guide for decision making in distal radius fractures in patients older than 50 years and to retrospectively analyze its ability to predict treatment in 164 patients. METHODS: The present study consisted of 4 parts. The first part was a review of the literature to identify possible important factors that predict treatment outcome of distal radius fractures in patients 50 years old and older. The second part identified which of these first-tier factors that orthopedic surgeons consider to be important by a questionnaire that was sent to 83 orthopedic surgeons qualified by the Japanese Orthopedic Association with response rate of 61%. The third part further identified which of the subsets of factors best predict outcome in a retrospective study of 41 patients 50 years old or older, yielding a final subset of factors to create a scoring system. The fourth part of the study then evaluated the ability of this scoring system to predict the outcome as evaluated by the modified Mayo wrist score and the Disabilities of the Arm, Shoulder and Hand score in a retrospective study of 164 distal radius fractures in patients 50 years old or older. RESULTS: The 164 patients were divided into 4 groups by the present scoring system: conservative group, relative conservative group, relative surgical group, and surgical group according to the recommended therapeutic modalities. Clinical outcomes of those that followed the recommendation of the present scoring system resulted in favorable consequences. In contrast, the outcomes of those not following the recommendation were inferior. CONCLUSIONS: The present scoring system may be used as an easy-to-use decision-making tool when choosing conservative or surgical treatment for distal radius fractures.

The COX-2 selective blocker etodolac inhibits TNFα-induced apoptosis in isolated rabbit articular chondrocytes.

Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl- current (ICl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for the treatment of OA. In the present study, we examined in vitro effects of selective blockers of COX on the TNFα-induced activation of ICl,vol in rabbit chondrocytes using the patch-clamp technique. Exposure of isolated chondrocytes to TNFα resulted in an obvious increase in membrane Cl- conductance. The TNFα-evoked Cl- current exhibited electrophysiological and pharmacological properties similar to those of ICl,vol. Pretreatment of cells with selective COX-2 blocker etodolac markedly inhibited ICl,vol activation by TNFα as well as subsequent apoptotic events such as apoptotic cell volume decrease (AVD) and elevation of caspase-3/7 activity. In contrast, a COX-1 blocker had no effect on the decrease in cell volume or the increase in caspase-3/7 activity induced by TNFα. Thus, the COX-2-selective blocker had an inhibitory effect on TNFα-induced apoptotic events, which suggests that this drug would have efficacy for the treatment of OA.

RB1CC1 protein suppresses type II collagen synthesis in chondrocytes and causes dwarfism.

RB1-inducible coiled-coil 1 (RB1CC1) functions in various processes, such as cell growth, differentiation, senescence, apoptosis, and autophagy. The conditional transgenic mice with cartilage-specific RB1CC1 excess that were used in the present study were made for the first time by the Cre-loxP system. Cartilage-specific RB1CC1 excess caused dwarfism in mice without causing obvious abnormalities in endochondral ossification and subsequent skeletal development from embryo to adult. In vitro and in vivo analysis revealed that the dwarf phenotype in cartilaginous RB1CC1 excess was induced by reductions in the total amount of cartilage and the number of cartilaginous cells, following suppressions of type II collagen synthesis and Erk1/2 signals. In addition, we have demonstrated that two kinds of SNPs (T-547C and C-468T) in the human RB1CC1 promoter have significant influence on the self-transcriptional level. Accordingly, human genotypic variants of RB1CC1 that either stimulate or inhibit RB1CC1 transcription in vivo may cause body size variations.

In-advance trans-medullary stimulation of bone marrow enhances spontaneous repair of full-thickness articular cartilage defects in rabbits.

Mesenchymal stromal cells (MSCs), especially those lying close to cartilage defects, are an important cell source for cartilage regeneration. We hypothesize that a larger number of MSCs might become available, if the bone marrow in the immediate vicinity of the subchondral bone is stimulated for MSCs in advance of the creation of cartilage defects. A trans-medullary passage-way reaching the immediate vicinity of the subchondral bone was created 4 days prior to the creation of cartilage defects. In another setting, basic fibroblast growth factor (bFGF) was administered through the trans-medullary passage-way in order to augment the stimulation of MSCs. The rabbits were killed at various times after the creation of cartilage defects. Triple staining of bromodeoxyuridine (BrdU), CD44 and CD45 and histological evaluation were subsequently performed. A considerable proportion of the proliferating cells were identified as bone-marrow-derived MSCs. Enumeration of BrdU-positive cells demonstrated that trans-medullary stimulation, especially with bFGF, increased the number of proliferating cells. The histological grading score of trans-medullary stimulation with bFGF group was superior to that of the other groups. Thus, in-advance stimulation of the bone marrow effectively increases the number of proliferating cells. The putative progenitor cells for chondrocytes stimulated thereby are likely to be recruited to the osteochondral defects at the appropriate time, contributing to the repair of full-thickness articular cartilage defects at the early follow-up time point.

Relation of low-intensity pulsed ultrasound to the cell density of scaffold-free cartilage in a high-density static semi-open culture system.

BACKGROUND: A scaffold-free cartilage construct, analogous to those found during embryonic precartilage condensation, has received much attention as a novel modality for tissue-engineered cartilage. In the present study, we developed an uncomplicated culture system by which scaffold-free cartilage-like tissues are produced using cell-cell interactions. With this system, we attempted to prevent dedifferentiation and reverse the phenotypic modulations by adjusting the cell density. We investigated whether low-intensity pulsed ultrasound (LIPUS) enhances matrix synthesis of the scaffold-free cartilage construct. METHODS: Rat articular chondrocytes multiplied in monolayers were seeded onto the synthetic porous membrane at stepwise cell densities (i.e., 1.0, 2.0, and 4.0 × 10(7) cells/cm(2)) to allow formation of a scaffold-free cartilage construct via cell-cell interaction. The cartilage constructs were then stimulated by LIPUS for 20 min/day. To investigate the effect of LIPUS stimulation on matrix synthesis, expression of mRNA for cartilage matrix molecules was quantified by a real-time reverse transcription-polymerase chain reaction. Synthesis of type II collagen, type I collagen, and proteoglycan was also assessed histologically. RESULTS: Only the chondrocytes cultured at high cell densities in the 2.0 × 10(7)cells/cm(2) group became concentrated and formed a plate-like construct similar to native articular cartilage by macroscopic and histological assessments. Statistical analysis on the matrix gene expression demonstrated that the levels of type II collagen and aggrecan mRNA of the 2.0 × 10(7)cells/cm(2) group were significantly higher than with the other two cell-density groups. Interestingly, the LIPUS application led to a statistically significant enhancement of aggrecan gene expression only in the 2.0 × 10(7) cells/cm(2) group. CONCLUSIONS: The current study presents a semi-open static culture system that facilitates production of the scaffold-free constructs from monolayer-cultured chondrocytes. It suggests that the LIPUS application enhances matrix production in the construct, and its combination with the scaffold-free construct might become a feasible tool for production of implantable constructs of better quality.

Regulatory role of tyrosine phosphorylation in the swelling-activated chloride current in isolated rabbit articular chondrocytes.

Articular chondrocytes are exposed in vivo to the continually changing osmotic environment and thus require volume regulatory mechanisms. The present study was designed to investigate (i) the functional role of the swelling-activated Cl(-) current (I(Cl,swell)) in the regulatory volume decrease (RVD) and (ii) the regulatory role of tyrosine phosphorylation in I(Cl,swell), in isolated rabbit articular chondrocytes. Whole-cell membrane currents were recorded from chondrocytes in isosmotic, hyposmotic and hyperosmotic external solutions under conditions where Na(+), K(+) and Ca(2+) currents were minimized. The cell surface area was also measured using microscope images from a separate set of chondrocytes and was used as an index of cell volume. The isolated chondrocytes exhibited a RVD during sustained exposure to hyposmotic solution, which was mostly inhibited by the I(Cl,swell) blocker 4-(2-butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl)oxobutyric acid (DCPIB) at 20 microM. Exposure to a hyposmotic solution activated I(Cl,swell), which was also largely inhibited by 20 microM DCPIB. I(Cl,swell) in rabbit articular chondrocytes had a relative taurine permeability (P(tau)/P(Cl)) of 0.21. Activation of I(Cl,swell) was significantly reduced by the protein tyrosine kinase (PTK) inhibitor genistein (30 microM) but was only weakly affected by its inactive analogue daidzein (30 microM). Intracellular application of protein tyrosine phosphatase (PTP) inhibitor sodium orthovanadate (250 and 500 microM) resulted in a gradual activation of a Cl(-) current even in isosmotic solutions. This Cl(-) current was almost completely inhibited by 4,4-diisothiocyanatostilbene-2,2-disulfonate (DIDS, 500 microM) and was also largely suppressed by exposure to hyperosmotic solution, thus indicating a close similarity to I(Cl,swell). Pretreatment of chondrocytes with genistein significantly prevented the activation of the Cl(-) current by sodium orthovanadate, suggesting that the basal activity of endogenous PTK is required for the activation of this Cl(-) current. Our results provide evidence to indicate that activation of I(Cl,swell) is involved in RVD in isolated rabbit articular chondrocytes and is facilitated by tyrosine phosphorylation.

The recovery of 5-HT transporter and 5-HT immunoreactivity in injured rat spinal cord.

STUDY DESIGN: Experimental spinal cord injury. OBJECTIVE: To determine the role of serotonin (5-HT) and 5-HT transporter in recovery from spinal cord injury. METHOD: We examined 5-HT and 5-HT transporter of spinal cord immunohistologically and assessed locomotor recovery after extradural compression at the thoracic (T8) spinal cord in 21 rats. Eighteen rats had laminectomy and spinal cord injury, while the remaining three rats received laminectomy only. All rats were evaluated every other day for 4 weeks, using a 0-14 point scale open field test. RESULTS: Extradural compression markedly reduced mean hindlimbs scores from 14 to 1.5 +/- 2.0 (mean +/- standard error of mean). The rats recovered apparently normal walking by 4 weeks. The animals were perfused with fixative 1-3 days, 1, 2 and 4 weeks (three rats in each) after a spinal cord injury. The 5-HT transporter immunohistological study revealed a marked reduction of 5-HT transporter-containing terminals by 1 day after injury. By 4 weeks after injury, 5-HT transporter immunoreactive terminals returned to the control level. The 5-HT immunohistological study revealed a reduction of 5-HT-containing terminals by 1 week after injury. By 4 weeks after injury, 5-HT immunoreactive fibers and terminals returned to the control level. CONCLUSION: We estimated the recovery of 5-HT transporter and 5-HT neural elements in lumbosacral ventral horn by ranking 5-HT transporter and 5-HT staining intensity and counting 5-HT and 5-HT transporter terminals. The return of 5-HT transporter and 5-HT immunoreactivity of the lumbosacral ventral horn correlated with locomotor recovery, while 5-HT transporter showed closer relationship with locomotor recovery than 5-HT. The presence of 5-HT transporter indicates that the 5-HT fibers certainly function. This study shows that return of the function of 5-HT fibers predict the time course and extent of locomotory recovery after thoracic spinal cord injury.

Effect of dynamic compressive loading and its combination with a growth factor on the chondrocytic phenotype of 3-dimensional scaffold-embedded chondrocytes.

BACKGROUND AND PURPOSE: Three-dimensionally (3D-) embedded chondrocytes have been suggested to maintain the chondrocytic phenotype. Furthermore, mechanical stress and growth factors have been found to be capable of enhancing cell proliferation and ECM synthesis. We investigated the effect of mechanical loading and growth factors on reactivation of the 3D-embedded chondrocytes. METHODS: Freshly isolated chondrocytes from rat articular cartilage were grown in monolayer cultures and then in collagen gel. Real-time RT-PCR and histological analysis for aggrecan and type II and type I collagen was performed to evaluate their chondrocytic activity. Then, the 3D-embedded chondrocytes were cultured under either mechanical loading alone or in combination with growth factor. The dynamic compression (5% compression, 0.33 Hz) was loaded for 4 durations: 0, 10, 60, and 120 min/day. The growth factor administered was either basic fibroblast growth factor (bFGF) or bone morphogenetic protein-2 (BMP-2). RESULTS: Mechanical loading statistically significantly reactivated the aggrecan and type II collagen expression with loading of 60 min/day as compared to the other durations. The presence of BMP-2 and bFGF clearly enhanced the aggrecan and type II collagen expression of 3D-embedded chondrocytes. Unlike previous reports using monolayer chondrocytes, however, BMP-2 or bFGF did not augment the chondrocytic phenotype when applied together with mechanical loading. INTERPRETATION: Dynamic compression effectively reactivated the dedifferentiated chondrocytes in 3D culture. However, the growth factors did not play any synergistic role when applied with dynamic compressive loading, suggesting that growth factors should be administered at different time points during regeneration of the transplantation-ready cartilage.

Percutaneous transthoracic fenestration of an intramedullary neurenteric cyst in the thoracic spine with intraoperative magnetic resonance image navigation and thoracoscopy.

Neurenteric cysts are rare congenital cysts typically located in the anterior cervical or thoracic spinal canal. The authors report on their experience with the successful treatment of a midthoracic neurenteric cyst in an 8-year-old boy. Percutaneous fenestration via a transthoracic, transvertebral approach with combined thorascopy and intraoperative MR imaging guidance was used, and the cyst showed lasting shrinkage. The authors discuss this minimally invasive technique and its limitations.

Intrasynovial lipoma causing trigger wrist and carpal tunnel syndrome.

Triggering of the flexor tendon at the wrist is rare. We report a case of intrasynovial lipoma that caused a trigger wrist. As far as we know it is unique in that the intrasynovial lipoma simultaneously caused carpal tunnel syndrome. The massive tenosynovitis and adhesion of flexors tendons after the locking of the intrasynovial lipoma may have resulted from inflammation caused by attrition within the carpal tunnel.

The MR tracking of transplanted ATDC5 cells using fluorinated poly-L-lysine-CF3.

Magnetic resonance (MR) imaging using super-paramagnetic iron oxides (SPIOs) is a powerful tool to monitor transplanted cells in living animals. However, since SPIOs are negative contrast agents it is difficult to track transplanted cells in bone and cartilage that originally display low signals. In this study, we examined the feasibility of tracking with fluorescein isothiocyanate (FITC)-labeled poly-L-lysine-CF(3) (PLK-CF(3)) using mouse ATDC5 cells, a stem cell line of bone and cartilage cells. FITC-labeled PLK-CF(3) was easily internalized by ATDC5 cells by adding it into culture medium. No acute or long-term toxicities were seen at less than 160 microg/ml. Labeled cells transplanted into the cranial bone of mice were detected for at least 7 days by MR images. FITC-labeled PLK-CF(3) is a useful positive contrast agent for MR tracking in bone and cartilage.