[Therapeutic utilization of stem cells in orthopedics]. / Therapeutische Anwendung von Stammzellen in der Orthopädie.

Stem cells are becoming increasingly more important in the field of regenerative medicine. Adult mesenchymal stem cells (MSCs) are harvested predominantly from bone marrow or adipose tissue, are already being used in the clinical setting and have a low potential for side effects. In orthopedics, experience has been gained in the treatment of bone defects, non-unions, cartilage defects, osteoarthritis and tendon pathologies. The current data are derived from case studies and randomized controlled trials are missing; therefore, there are many open questions concerning the optimal cell source, number of cells, administration technique (e.g. injections and matrices) or combinations with growth factors; however, it is evident from the data that MSCs have a positive effect on tissue regeneration and are safe to use.

Matrix-associated autologous chondrocyte transplantation in a compartmentalized early stage of osteoarthritis.

OBJECTIVE: Cartilage restoration in joints with an early stage of osteoarthritis (OA) is an important clinical challenge. In this study, a compartmentalized, early-stage OA was generated surgically in sheep stifle joints, and this model was used to evaluate a matrix-associated cell transplantation approach for cartilage repair. METHOD: Eighteen sheep were operated twice. During the first operation, a unicompartmental OA in a stable joint was induced by creating a critical-size defect. The second operation served as a regeneration procedure. The eighteen sheep were divided into three groups. One group was treated with spongialization (SPONGIO), while the two others had spongialization followed by implantation of a hyaluronan matrix with (MACT) or without chondrocytes (MATRIX). The follow-up took place 4 months after the second operation. Gross Assessment of Joint Changes score and Brittberg score were used for the macroscopic evaluation, Mankin score, O'Driscoll score, and immunohistochemistry for collagen type I and type II for histological evaluation. RESULTS: The MACT group achieved significantly better results in both macroscopic and histological examinations. In the regeneration area, a Mankin score of 7.88 (6.20; 9.55) [mean (upper 95% confidence interval; lower 95% confidence interval)] was reached in the MACT group, 10.38 (8.03; 12.72) in the MATRIX group, and 10.33 (8.80; 11.87) in the SPONGIO group. The O'Driscoll score revealed a highly significant difference in the degree of defect repair: 15.92 (14.58; 17.25) for the MACT group compared to the two other groups [5.04 (1.21; 8.87) MATRIX and 6.58 (5.17; 8.00) SPONGIO; P < 0.0001]. CONCLUSION: This study demonstrates promising results toward the development of a biological regeneration technique for early-stage OA.

Patterns of joint damage seen on MRI in early hip osteoarthritis due to structural hip deformities.

OBJECTIVE: The aim of this study was to evaluate differences in damage patterns assessed using magnetic resonance imaging (MRI) between hips with femoroacetabular impingement (FAI) and developmental dysplasia of the hip (DDH) as well as to correlate MRI findings with delayed Gadolinium enhanced MRI of cartilage (dGEMRIC) and with patient pain. DESIGN: This retrospective study included 40 patients (mean age 28.6 ± 11.2 years) who underwent dGEMRIC and morphological MRI of the hip. Twenty-one hips with FAI and 19 with DDH were investigated. A self-developed morphological grading (MRI score) and dGEMRIC evaluation were done on seven radial reformats obtained from an isotropic 3D True-fast imaging with steady state precession (FISP) sequence and an isotropic T1-mapping sequence. The observed damage patterns were summed up into sub-scores and a total MRI score. RESULTS: Labrum damage, paralabral cysts, and acetabular rim bone cysts were more common in DDH patients than in FAI patients. No significant differences were seen in the occurrence of cartilage damage, bone cysts, or osteophytes. In DDH (but not in FAI), the dGEMRIC index demonstrated a tendency for lower values in areas next to cartilage defects. There was no association between labrum damage and dGEMRIC index. A moderate correlation was seen between Western Ontario and McMaster Universities (WOMAC) pain score and cartilage damage, paralabral cysts, and the total MRI score. CONCLUSIONS: This study confirms a higher prevalence of labrum damage but not cartilage damage in patients with DDH in comparison to patients with FAI. In addition, our data suggests an association of cartilage damage and paralabral cysts with patient reported pain.

Assessment of articular cartilage repair tissue after matrix-associated autologous chondrocyte transplantation or the microfracture technique in the ankle joint using diffusion-weighted imaging at 3 Tesla.

OBJECTIVE: The objective was to compare patients after matrix-associated autologous chondrocyte transplantation (MACT) and microfracture therapy (MFX) of the talus using diffusion-weighted imaging (DWI), with morphological and clinical scoring. MATERIALS AND METHODS: Twenty patients treated with MACT or MFX (10 per group) were examined using 3 T magnetic resonance imaging (MRI) at 48 ± 21.5 and 59.6 ± 23 months after surgery, respectively. For comparability, patients from each group were matched by age, body mass index, and follow-up. American Orthopaedic Foot and Ankle Society (AOFAS) score served as clinical assessment tool pre- and postoperatively. DWI was obtained using a partially balanced, steady-state gradient echo pulse sequence, as well as the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, based on a 2D proton density-weighted turbo spin-echo sequence and a 3D isotropic true fast imaging with steady-state precession sequence. Semi-quantitative diffusion quotients were calculated after region of interest analysis of repair tissue (RT) and healthy control cartilage, and compared among both groups. RESULTS: The mean AOFAS score improved significantly (P = 0.001) for both groups (MACT: 48.8 ± 20.4-83.6 ± 9.7; MFX: 44.3 ± 16.5-77.6 ± 13.2). No differences in the AOFAS (P = 0.327) and MOCART (P = 0.720) score were observed between MACT and MFX postoperatively. DWI distinguished between healthy cartilage and cartilage RT in the MFX group (P = 0.016), but not after MACT treatment (P = 0.105). Significant correlations were found between MOCART score and DWI index after MFX (Pearson: -0.648; P = 0.043), and between the diffusivity and longer follow-up interval in MACT group (Pearson: -0.647, P = 0.043). CONCLUSION: Whereas conventional scores reveal a similar outcome after MACT or MFX treatment in the ankle joint, DWI was able to distinguish between different RT qualities, as reported histologically for these diverse surgical procedures.

Cartilage repair of the ankle: first results of T2 mapping at 7.0 T after microfracture and matrix associated autologous cartilage transplantation.

BACKGROUND: Both microfracture (MFX) and matrix associated autologous cartilage transplantation (MACT) are currently used to treat cartilage defects of the talus. T2 mapping of the ankle at 7 T has the potential to assess the collagen fibril network organization of the native hyaline cartilage and of the repair tissue (RT). This study provides first results regarding the properties of cartilage RT after MFX (mean follow-up: 113.8 months) and MACT (65.4 months). METHODS: A multi-echo spin-echo sequence was used at 7 T to assess T2 maps in 10 volunteer cases, and in 10 cases after MFX and MACT each. Proton weighted morphological images and clinical data were used to ensure comparable baseline criteria. RESULTS: A significant zonal variation of T2 was found in the volunteers. T2 of the superficial and the deep layer was 39.3 ± 5.9 ms and 21.1 ± 3.1 ms (zonal T2 index calculated by superficial T2/deep T2: 1.87 ± 0.2, P < 0.001). In MFX, T2 of the reference cartilage was 37.4 ± 5.0 ms and 25.3 ± 3.5 ms (1.51 ± 0.3, P < 0.001). In the RT, T2 was 43.4 ± 10.5 ms and 36.3 ± 7.7 ms (1.20 ± 0.2, P = 0.009). In MACT, T2 of the reference cartilage was 39.0 ± 9.1 ms and 27.1 ± 6.6 ms (1.45 ± 0.2, P < 0.001). In the RT, T2 was 44.6 ± 10.4 ms and 38.6 ± 7.3 ms (1.15 ± 0.1, P = 0.003). The zonal RT T2 variation differed significantly from the reference cartilage in both techniques (MFX: P = 0.004, MACT: P = 0.001). CONCLUSION: T2 mapping at 7 T allows for the quantitative assessment of the collagen network organization of the talus. MACT and MFX yielded RT with comparable T2 properties.

Evaluation of native hyaline cartilage and repair tissue after two cartilage repair surgery techniques with 23Na MR imaging at 7 T: initial experience.

OBJECTIVE: To compare the sodium normalized mean signal intensity (NMSI) values between patients after bone marrow stimulation (BMS) and matrix-associated autologous chondrocyte transplantation (MACT) cartilage repair procedures. METHODS: Nine BMS and nine MACT patients were included. Each BMS patient was matched with one MACT patient according to age [BMS 36.7 ± 10.7 (mean ± standard deviation) years; MACT 36.9 ± 10.0 years], postoperative interval (BMS 33.5 ± 25.3 months; MACT 33.2 ± 25.7 months), and defect location. All magnetic resonance imaging (MRI) measurements were performed on a 7 T system. Proton images served for morphological evaluation of repair tissue using the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system. Sodium NMSI values in the repair area and morphologically normal cartilage were calculated. Clinical outcome was assessed right after MRI. Analysis of covariance, t-tests, and Pearson correlation coefficients were evaluated. RESULTS: Sodium NMSI was significantly lower in BMS (P = 0.004) and MACT (P = 0.006) repair tissue, compared to reference cartilage. Sodium NMSI was not different between the reference cartilage in MACT and BMS patients (P = 0.664), however it was significantly higher in MACT than in BMS repair tissue (P = 0.028). Better clinical outcome was observed in BMS than in MACT patients. There was no difference between MOCART scores for MACT and BMS patients (P = 0.915). We did not observe any significant correlation between MOCART score and sodium repair tissue NMSI (r = -0.001; P = 0.996). CONCLUSIONS: Our results suggest higher glycosaminoglycan (GAG) content, and therefore, repair tissue of better quality in MACT than in BMS patients. Sodium imaging might be beneficial in non-invasive evaluation of cartilage repair surgery efficacy.

[Biochemical magnetic resonance imaging of intervertebral discs and facet joints]. / Biochemische MR-bildgebung der bandscheibe und facettengelenke der wirbelsäule.

The limited specificity of standard magnetic resonance imaging (MRI) in patients with low back pain encourages the development of new imaging techniques. Quantitative MR methods have the potential to assess biochemical changes of spinal structures in vivo. Early diagnosis of intervertebral disc and facet joint changes in young to middle aged patients allows the use of a specific therapy and preventative measures. Potential techniques are T2 and T2* mapping, diffusion-weighted imaging, magnetization transfer imaging, T1ρ mapping, sodium imaging and MR spectroscopy. Well designed longitudinal therapy studies, which assess biochemical and clinical parameters, are necessary. High-field MR systems (3 Tesla) are needed for high resolution biochemical MRI and clinically reasonable scan times.

Quantitative T2 mapping of the patella at 3.0T is sensitive to early cartilage degeneration, but also to loading of the knee.

OBJECTIVE: The aim of the study was to explore the sensitivity and robustness of T2 mapping in the detection and quantification of early degenerative cartilage changes at the patella. MATERIALS AND METHODS: Forty-two patients (22 women, 20 men) with a mean age of 30.3 years and a symptomatic cartilage defect of ICRS grade ≤2 were examined using a 3T MRI with an 8-channel knee coil. The cartilage lesion was graded based on high-resolution PD TSE and 3D isotropic TrueFISP images. T2 maps were calculated from a standard MESE-sequence, performed at the beginning and at the end of the scan (40min in-between). Depending on the defect size, a region-of-interest (ROI) analysis was performed on 1-3 consecutive slices. Mean T2 values for the deep, superficial, and global layer as well as the zonal variation were compared among defect grades (ANOVA, post hoc Duncan-test) and over time (Student's t-test). RESULTS: T2-measurements directly correlated with the extent of cartilage defect (ICRS grade) at all layers and at both time-points. However, correlations were closer for the second measurement at the end of the scan. In this unloaded state, differences in T2-values became more pronounced and were significant even between cartilage of normal appearance adjacent to the defect and healthy cartilage of control patients (both ICRS grade 0). In contrast, there were no such differences among grades in the zonal variation at any time. CONCLUSION: T2 mapping might be a sensitive method for the detection of early cartilage degeneration at the patella in the unloaded joint.

Microfracture in the Ankle: Clinical Results and MRI with T2-Mapping at 3.0 T after 1 to 8 Years.

BACKGROUND: Microfracture (MFX) is frequently used to treat deep cartilage defects in the ankle; however, the data on repair tissue (RT) quality after MFX are very limited at this time. T2-mapping at 3 T has been optimized for the ankle and can be used to noninvasively evaluate cartilage collagen and water content. The aim of this study was to determine if the RT after MFX in the ankle had T2 properties similar to the adjacent reference cartilage (RC). METHODS: Fourteen cases after MFX in the ankle were assessed with morphological MRI and T2-mapping at 3 T. The American Orthopaedic Foot and Ankle Society (AOFAS) score and a modified Cinicinnati Knee Rating System rating were used to evaluate the clinical outcome. The MRI protocol included a 3-dimensional sequence and a proton-density sequence for morphological evaluation and a multiecho spin echo sequence for T2-mapping. Region of interest analyses were carried out in accordance with the morphological images to ensure complete coverage of the defect site. RESULTS: Both clinical scores demonstrated significant improvement at the time of the MR examination (P < 0.001). RT T2 was 49.3 ± 10.1 (range, 35.7-69.3) milliseconds, and RC T2 was 49.9 ± 8.2 (range, 38.4-63.7) milliseconds (P = 0.838). Relative T2 (rT2) was 1.00 ± 0.20 (range, 0.72-1.36). CONCLUSION: MFX in the ankle can provide RT with T2 properties similar to adjacent cartilage.

Interactions of glucose metabolism and chronic heart failure.

BACKGROUND: We evaluated insulin sensitivity and beta cell function in patients with chronic heart failure (CHF), and investigated a possible correlation of these metabolic parameters with specific biomarkers of heart failure. Additionally, we investigated the effects of two angiotensin receptor blockers (ARBs), namely telmisartan and candesartan, that were administered over a 5 month treatment period, as additional therapy to standard care. METHODS AND RESULTS: The study group consisted of 94 CHF patients. Insulin sensitivity (OGIS index) and insulin secretion parameters were investigated by frequently sampled oral glucose tolerance tests and consecutive mathematical modelling. In total, 94.6 % of patients had clinically overt diabetes, impaired glucose tolerance or insulin resistance at the time of enrolment HbA1c was found to correlate to NT-proBNP, MR-proADM, CT-proET-1, and MR-proANP, but not to Copeptin. NT-proBNP correlated inversely to OGIS. None of the metabolic parameters were altered significantly after candesartan or telmisartan treatment in either the patient or standard care group. CONCLUSION: Insulin sensitivity and insulin secretion are impaired in CHF and biomarkers of heart failure and atherosclerotic disease correlate to glucose metabolism.