Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics

Purpose

The aim of this systematic review is to examine the available clinical evidence in the literature to support mesenchymal stem cell (MSC) treatment strategies in orthopaedics for cartilage defect regeneration.

Methods

The research was performed on the PubMed database considering the English literature from 2002 and using the following key words: cartilage, cartilage repair, mesenchymal stem cells, MSCs, bone marrow concentrate (BMC), bone marrow-derived mesenchymal stem cells, bone marrow stromal cells, adipose-derived mesenchymal stem cells, and synovial-derived mesenchymal stem cells.

Results

The systematic research showed an increasing number of published studies on this topic over time and identified 72 preclinical papers and 18 clinical trials. Among the 18 clinical trials identified focusing on cartilage regeneration, none were randomized, five were comparative, six were case series, and seven were case reports; two concerned the use of adipose-derived MSCs, five the use of BMC, and 11 the use of bone marrow-derived MSCs, with preliminary interesting findings ranging from focal chondral defects to articular osteoarthritis degeneration.

Conclusions

Despite the growing interest in this biological approach for cartilage regeneration, knowledge on this topic is still preliminary, as shown by the prevalence of preclinical studies and the presence of low-quality clinical studies. Many aspects have to be optimized, and randomized controlled trials are needed to support the potential of this biological treatment for cartilage repair and to evaluate advantages and disadvantages with respect to the available treatments.

Level of evidence

IV.     

Chylotamponade: an unusual presentation of Gorham's syndrome

Gorham's Syndrome, also known as massive osteolysis or "vanishing bone disease" results from lymphangiomatosis with adjacent bone resorption. Chylothorax is a common complication in cases of mediastinal involvement. We report a case of Gorham's Syndrome presenting as chylotamponade successfully treated with pericardial drainage, early parenteral nutritional support, bilateral pleurodesis for chylous effusions, and adjuvant external beam radiation.     

Prospective, Randomized, Multi-Center Trial of Antibody Induction Therapy in Simultaneous Pancreas-Kidney Transplantation

A randomized, multicenter, prospective study was conducted at 18 pancreas transplant centers in the United States to determine the role of induction therapy in simultaneous pancreas-kidney (SPK) transplantation. One hundred and 74 recipients were enrolled: 87 recipients each in the induction and noninduction treatment arms. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and corticosteroids. There were no statistically significant differences between treatment groups for patient, kidney, and pancreas graft survival at 1-year. The 1-year cumulative incidence of any treated biopsy-confirmed or presumptive rejection episodes (kidney or pancreas) in the induction and noninduction treatment arms was 24.6% and 31.2% (p = 0.28), respectively. The 1-year cumulative incidence of biopsy-confirmed, treated, acute kidney allograft rejection in the induction and noninduction treatment arms was 13.1% and 23.0% (p = 0.08), respectively. Biopsy-confirmed kidney allograft rejection occurred later post-transplant and appeared to be less severe among recipients that received induction therapy. The highest rate of Cytomegalovirus (CMV) viremia/syndrome was observed in the subgroup of recipients who received T-cell depleting antibody induction and received organs from CMV serologically positive donors. Decisions regarding the routine use of induction therapy in SPK transplantation must take into consideration its differential effects on risk of rejection and infection.     

Caffeine in children with obstructive sleep apnea

BACKGROUND: Children with obstructive sleep apnea (OSA) have a higher rate of adverse post-extubation respiratory events, such as laryngospasm, upper airway obstruction, apnea, desaturation and/or need for re-intubation. They are overly sensitive to sedatives and narcotics. Although the etiology of OSA is primarily obstruction (mechanical or neuromuscular), a central element may contribute to OSA. Caffeine citrate has been shown to be effective in treating apnea of prematurity. This study evaluated whether the administration of caffeine benzoate to children with OSA decreases the number of children who experience adverse post-extubation respiratory events. METHODS: In a randomized, double-blind and placebo-controlled study, children with OSA scheduled for adenotonsillectomy (T&A) received either caffeine benzoate, 20 mg/kg IV, (caffeine group, n = 36) or saline (placebo group, n = 36). The primary outcome evaluated the number of children who developed adverse post-extubation respiratory events, and the secondary outcome was the incidence of those events. RESULTS: The results demonstrated the two groups differed in the number of children who developed adverse post-extubation respiratory events (p = 0.032). The overall incidence of adverse postoperative respiratory events was less in the caffeine group than the placebo group (p = 0.0196). CONCLUSION: In children with OSA scheduled for T&A, administration of caffeine benzoate, 20 mg/kg IV, decreased the number of children who developed adverse post-extubation respiratory events and decreased the overall incidence of adverse post-extubation respiratory events. PACU duration, hospital discharge time and postoperative delirium did not differ between groups.     

The characteristics of Hep-2 cell with multiple drug resistance induced by Taxol.

OBJECTIVE: To investigate the characteristics of Hep-2 cell with multidrug resistance (MDR) induced by Taxol. STUDY DESIGN: Hep-2 cells were exposed in stepwise escalating concentration of Taxol to develop the resistant cell line-Hep-2T. Cell cycle distribution, apoptosis, and rhodamine accumulation were studied through flow cytometry. The MDR1 and MRP1 genes were detected through real-time quantitative RT-PCR, and the corresponding proteins were detected through Western blotting. RESULTS: The drug resistance of Hep-2T cells to Taxol, doxorubicin, gemcitabine, 5-FU, and cisplatin all increased. The percentage of G0/G1 phase and the antiapoptosis ability increased significantly compared with Hep-2 cells. Both MDR1 and MRP1 also increased at gene and protein level, though MDR1 was more prominent. CONCLUSION: More emphasis should be laid on MDR1/Pgp, the non-Pgp substrate chemotherapeutic agents, and the changes of cell cycle distribution to prevent MDR induced by Taxol. SIGNIFICANCE: These findings may provide theoretical support for the reverse of MDR.     

Prevalence of lower urinary tract symptoms among female elementary school teachers in Taipei

The aim of this study was to estimate the prevalence of lower urinary tract symptoms (LUTS) among female elementary school teachers in Taipei. A total of 520 self-administered surveys were distributed to 26 elementary schools in Taipei City. Data analyses were based on 445 usable surveys. The prevalence rates for different types of LUTS ranged from 9.9 to 44.5%. The prevalence of urinary incontinence (UI; 26.7%) and nocturia (16.0%) fell within the prevalence estimates of these LUTS in North American and European women. Employed women in this study were more likely to experience LUTS than women in previous epidemiological or community studies. This study extended research on UI into other LUTS among employed women in Asia. Study results suggest that the working environment may affect LUTS in female elementary school teachers. This preliminary study is important for developing future behavioral interventions for female LUTS in the workplace.     

Prognosis and Results After Resection of Very Large (≥10 cm) Hepatocellular Carcinoma

Introduction Few potentially curative treatment options exist besides resection for patients with very large (≥10 cm) hepatocellular carcinoma (HCC). We sought to examine the outcomes and risk factors for recurrence after resection of ≥10 cm HCC. Methods Perioperative and long-term outcomes were examined for 189 consecutive patients from 1993 to 2004 who underwent potentially curative resection of HCC ≥10 cm (n = 24; 13%) vs. those with HCC <10 cm (n = 165; 87%). Disease-free survival (DFS) and overall survival (OS) were determined by Kaplan–Meier analysis and patient, tumor, and treatment characteristics were compared using univariate and multivariate analysis. Results Median follow-up was 34 months. Tumors ≥10 cm were more likely to be symptomatic, of poorer grade, and have vascular invasion (p < 0.05). Twelve patients (50%) underwent an extended resection of more than four hepatic segments or resection of adjacent organs for oncologic clearance (diaphragm-2, inferior vena cava (IVC)-2, median sternotomy-1). Postoperative complications were more common after resection of >10 cm HCC (12/24, 50% vs. 35/165, 21%; p = 0.04). Median DFS was significantly shorter in patients with large HCC (≥10 cm) group compared to patients with smaller HCC (8.4 vs. 38 months; p = 0.001), but overall survival was not different between the two groups (5-year survival 54% vs. 53%; p = 0.43). Seventeen patients (71%) with very large HCC developed recurrences (12 intrahepatic, five systemic); eight of these patients (47%) underwent additional therapy (resection-4, TACE-3, RFA-1). Pathological positive margins and vascular invasion were significant determinants of DFS in tumors ≥10 cm (p < 0.05), but only vascular invasion was an independent risk factor for recurrence after multivariate analysis (HR 0.17; 95% CI: 0.04–0.8). Median OS after recurrence was 24 months. Conclusion Surgical resection is the optimal therapy for very large (≥10 cm) HCC. Although recurrences are common after resection of these tumors, overall survival was not significantly different from patients after resection of smaller HCC in this series. Presented at the 2006 American Hepato-Pancreatico-Biliary Congress, Miami, FL, March 9–12, 2006.     

Autotransfusion management during and after cardiopulmonary bypass alters fibrin degradation and transfusion requirements

The coagulation-fibrinolytic profile during cardiopulmonary bypass (CPB) has been widely documented. However, less information is available on the possible persistence of these alterations when autotransfusion is used in management of perioperative blood loss. This study was designed to explore the influence of autotransfusion management on intravascular fibrin degradation and postoperative transfusions. Thirty patients, undergoing elective primary isolated coronary bypass grafting, were randomly allocated either to a control group (group A; n=15) or an intervention group (group B; n=15) in which mediastinal and residual CPB blood was collected and processed by a continuous autotransfusion system before re-infusion. Intravascular fibrin degradation as indicated by D-dimer generation was measured at five specific intervals and corrected for hemodilution. In addition, chest tube drainage and need for homologous blood were monitored. D-dimer generation increased significantly during CPB in group A, from 312 to 633 vs. 291 to 356 ng/mL in group B (p = .001). The unprocessed residual blood (group A) revealed an unequivocal D-dimer elevation, 4131 +/- 1063 vs. 279 +/- 103 ng/mL for the processed residual in group B (p < .001). Consequently, in the first post-CPB period, the intravascular fibrin degradation was significantly elevated in group A compared with group B (p = .001). Twenty hours postoperatively, no significant difference in D-dimer levels was detected between both groups. However, a significant intra-group D-dimer elevation pre- vs. postoperative was noticed from 312 to 828 ng/mL in group A and from 291 to 588 ng/mL in group B (p < .01 for both). Postoperative chest tube drainage was higher in the patients from group A, which also had the highest postoperative D-dimer levels. Patients in group A perceived a higher need for transfusions of red cells suspensions postoperatively. These data clearly indicate that autotransfusion management during and after CPB suppresses early postoperative fibrin degradation. Keywords: cardiopulmonary bypass, cardiotomy suction, coronary surgery, autotransfusion, fibrin degradation.     

Mutant mice provide new insight into the role of (mis-)glycation in IgA nephropathy and other glomerular diseases.

In the 24 October 2006 issue of PNAS, Alexander and colleagues[1] describe the results of a systematic search for thrombocytopenicmice generated by large-scale mutagenesis. Amongst 3523 mice,one pedigree indeed exhibited 50% reduction in platelet counts.Apart from thrombocytopenia, the only other notable featureof these mice was prominent renal disease (albuminuria/proteinuria,glomerulosclerosis and tubulointerstitial inflammatory infiltration)leading to uraemia and death at around 200 days after birth.This renal disease was not immune mediated, since it persistedin mutant mice crossed to     

Longitudinal followup study of ultrasonography in congenital muscular torticollis

High-resolution ultrasonography was used to examine affected sternocleidomastoid muscles in patients with congenital muscular torticollis at different times. Thirty-one female and 42 male patients were recruited and classified as having one of four types of fibrosis based on the sonograms. Compared with initial assessment, 22 (95.6%) patients with Type I fibrosis and 22 (57.9%) patients with Type II fibrosis had a change in classification at the end of the study. Among the patients with Type I fibrosis, the classification of one patient was changed to Type III fibrosis, the classifications of two patients were changed to normal muscle, and the classifications of the other patients were changed to Type II fibrosis. For patients with Type II fibrosis, the classifications of two patients were changed to Type III fibrosis, the classifications of three patients were changed to Type IV fibrosis, and the classifications of the other patients were changed to normal muscle. No changes in classification of patients with Types III and IV fibrosis occurred during followup. Patients with Type IV fibrosis had a significantly high incidence of surgical intervention. Congenital muscular torticollis is a dynamic disease. Ultrasonography can be valuable in observing the alteration. Aggressive management may be necessary for patients with Type IV fibrosis.