Arthroscopic Transplantation of Synovial Stem Cells Improves Clinical Outcomes in Knees With Cartilage Defects

Background

Transplantation of mesenchymal stem cells (MSCs) is one possible strategy to achieve articular cartilage repair. We previously reported that synovial MSCs were highly proliferative and able to undergo chondrogenesis. We also found that placing a suspension of synovial MSCs on a cartilage defect for 10 minutes promoted cartilage repair in rabbit and pig models. However, the in vivo efficacy of this approach has not been tested clinically.

Questions/purposes

We asked whether transplantation of synovial MSCs improves (1) MRI features, (2) histologic features, and (3) clinical evaluation scores in patients with cartilage defects in the knee?

Methods

Patients with a symptomatic single cartilage lesion of the femoral condyle were indicated for inclusion in our study, and between April 2008 and April 2011, 10 patients were enrolled in this study. All patients completed followups of 3 years or more. The average followup period was 52 months (range, 37–80 months). Synovial MSCs were expanded with 10% autologous human serum for 14 days after digestion. For transplantation, the patient was positioned so that the cartilage defect was facing upward, and synovial MSC suspension was placed on the cartilage defect with a syringe under arthroscopic control. The defect with the applied suspension then was held in the upward position for 10 minutes. Five patients underwent concomitant ACL reconstructions, among whom two had meniscus suturing performed simultaneously. For MRI quantification, the cartilage defect was scored from 0 to 5. Second-look arthroscopy was performed for four patients and biopsy specimens were evaluated histologically. Clinical outcome was assessed using the Lysholm score and Tegner Activity Level Scale at final followup. Comparisons of MRI and Lysholm scores before and after treatment for each patient were analyzed using the Wilcoxon signed-rank test.

Results

MRI score (median ± 95% CI) was 1.0 ± 0.3 before and 5.0 ± 0.7 after, and increased after treatment in each patient (p = 0.005). Second-look arthroscopy in four patients showed that the cartilage defect appeared to be qualitatively better in all cases. Histologic analyses showed hyaline cartilage in three patients and fibrous cartilage in one at the deep zone. The Lysholm score (median ± 95% CI) was 76 ± 7 before and 95 ± 3 after, and increased after treatment in each patient (p = 0.005). The Tegner Activity Level Scale did not decrease after treatment in each patient.

Conclusions

For this small initial case series, transplantation of synovial MSCs was effective in terms of MRI score, qualitative histology, and Lysholm score. The use of synovial MSCs has an advantage in that the cells can be prepared at passage 0 in only 14 days. Transplantation of synovial MSCs may be less invasive than mosaicplasty and autologous chondrocyte implantation. To conclusively show the effectiveness of this treatment requires comparative studies, especially with more established arthroscopic procedures, such as marrow stimulation techniques.

Level of Evidence

Level IV, therapeutic study.     

Serum Total Cholesterol Levels Would Predict Nosocomial Infections After Gastrointestinal Surgery

It has been suggested that total cholesterol levels and the use of statin medications are associated with the incidence of complications after gastrointestinal surgery. The aim of this study was to determine if preoperative total cholesterol levels are associated with a higher risk of postoperative infections and mortality. A total of 2211 patients undergoing general surgical procedures between December 2006 and November 2008 at Iizuka Hospital and between January 2010 and March 2012 at Jichi Medical University Hospital were reviewed. Multiple logistic regression models were used to evaluate serum total cholesterol and other variables as predictors of postoperative nosocomial infections. Serum total cholesterol concentrations lower than 160 mg/dl were associated with an increased incidence of superficial and deep incisional surgical site infections. Serum total cholesterol levels showed a reverse J-shaped relationship with the development of organ space surgical site infection and pneumonia. There was no discernible effect of serum cholesterol levels on the postoperative mortality observed in this cohort of patients. Decreased serum albumin was one of the strongest risk factors for the development of nosocomial infection after surgery. Postoperative pneumonia was not observed in patients taking statin medications whose cholesterol levels were <200 mg/dl. Serum total cholesterol may be a valid predictor of surgical outcome. Preoperative statin use may affect the development of postoperative pneumonia in patients with total cholesterol levels below 200 mg/dl.     

In situ Ca2+ dynamics of Purkinje fibers and its interconnection with subjacent ventricular myocytes

Purkinje fibers play essential roles in impulse propagation to the ventricles, and their functional impairment can become arrhythmogenic. However, little is known about precise spatiotemporal pattern(s) of interconnection between Purkinje-fiber network and the underlying ventricular myocardium within the heart. To address this issue, we simultaneously visualized intracellular Ca(2+) dynamics at Purkinje fibers and subjacent ventricular myocytes in Langendorff-perfused rat hearts using multi-pinhole type, rapid-scanning confocal microscopy. Under recording of electrocardiogram at room temperature spatiotemporal changes in fluo3-fluorescence intensity were visualized on the subendocardial region of the right-ventricular septum. Staining of the heart with either fluo3, acetylthiocholine iodide (ATCHI), or di-4-ANEPPS revealed characteristic structures of Purkinje fibers. During sinus rhythm (about 60 bpm) or atrial pacing (up to 3 Hz) each Purkinje-fiber exhibited spatiotemporally synchronous Ca(2+) transients nearly simultaneously to ventricular excitation. Ca(2+) transients in individual fibers were still synchronized within the Purkinje-fiber network not only under high-K(+) (8 mM) perfusion-induced Purkinje-to-ventricular (P-V) conduction delay, but also under unidirectional, orthodromic P-V block produced by 10-mM K(+) perfusion. While spontaneous, asynchronous intracellular Ca(2+) waves were identified in injured fibers of Purkinje network locally, surrounding fibers still exhibited Ca(2+) transients synchronously to ventricular excitation. In summary, these results are the first demonstration of intracellular Ca(2+) dynamics in the Purkinje-fiber network in situ. The synchronous Ca(2+) transients, preserved even under P-V conduction disturbances or under emergence of Ca(2+) waves, imply a syncytial role of Purkinje fibers as a specialized conduction system, whereas unidirectional block at P-V junctions indicates a substrate for reentrant arrhythmias.     

Colonoscopic Stigmata of 1 mm or Deeper Submucosal Invasion in Colorectal Cancer

Purpose  This study was designed to identify colonoscopic stigmata, indicating substantial invasion into the submucosa by T1 colorectal cancer with sessile morphology, including both flat and protruded types. Methods  A total of 111 Tis or T1 colorectal cancers were studied retrospectively. The lesions were divided into two groups: Group A (n = 83), Tis or T1 cancers with <1 mm submucosal invasion; and Group B (n = 28), T1 cancers with a ≥1 mm submucosal invasion. Printed photographs of the lesions were reviewed by five experienced colonoscopists who were blinded to histology. Deep depression, irregular surface, ulceration or erosion, fold convergence, and spontaneous bleeding were independently evaluated. Findings considered present by three or more reviewers were defined as positive. Kappa analysis was used to measure inter/intraobserver variability. Results  Positive rates of four findings but not fold convergence were significantly higher in Group B than in Group A. Irregular surface and spontaneous bleeding were significant independent predictors of ≥1 mm submucosal invasion, with diagnostic accuracies of 85.6 and 76.6 percent, respectively. Kappa analysis demonstrated fair-to-good inter/intraobserver agreement for spontaneous bleeding and fair-to-good intraobserver agreement for irregular surface. Conclusions  Irregular surface and spontaneous bleeding were colonoscopic stigmata, indicating ≥1 mm submucosal invasion in T1 colorectal cancer.