RESUMEN
BACKGROUND: Mesenchymal stem cells (MSCs) represent a promising alternative form of cell-based therapy for cartilage injury. However, the capacity of MSCs for chondrogenesis has not been fully explored. In particular, there is presently a lack of studies comparing the effectiveness of MSCs to conventional autologous chondrocyte (autoC) treatment for regeneration of full-thickness cartilage defects in vivo. HYPOTHESIS: Treatment with allogenic undifferentiated MSCs (alloMSCs) results in superior cartilage tissue regeneration profiles when compared with autoC for repair of focal articular cartilage defects. STUDY DESIGN: Controlled laboratory study. METHODS: Full-thickness articular cartilage defects were created on the weightbearing surface of the medial femoral condyles in both knees of New Zealand White rabbits (N = 30). Six weeks after the defect was induced, the right knee was treated with either alloMSCs (n = 12) or autoC (n = 18), while the left knee remained untreated (control). The rabbits were sacrificed at 6 months after treatment for assessment of cartilage tissue regeneration, which included the Brittberg morphologic score, histologic grading by O'Driscoll score, and quantitative analysis of glycosaminoglycans per total protein content. RESULTS: Apart from significantly higher Brittberg scores in the alloMSC treatment group (8.8 ± 0.8) versus the autoC treatment group (6.6 ± 0.8) (P = .04), both treatments showed similar cartilage regenerative profiles. All outcome measures were significantly higher in the treatment groups compared with their respective controls (P < .05). CONCLUSION: AlloMSCs have similar effectiveness as autoC for repair of focal cartilage defects. Both treatments resulted in superior tissue regeneration compared with untreated defects. CLINICAL RELEVANCE: The results have an implication of supporting the potential use of MSCs for cartilage repair after sports injuries or diseases, in view of similar efficacy but less patient morbidity and potential cost savings as compared with conventional autoC therapy.
Asunto(s)
Alginatos/farmacología , Cartílago Articular/lesiones , Cartílago Articular/cirugía , Condrocitos/trasplante , Traumatismos de la Rodilla/cirugía , Trasplante de Células Madre Mesenquimatosas/métodos , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Glicosaminoglicanos/metabolismo , Técnicas para Inmunoenzimas , Masculino , Conejos , Distribución Aleatoria , Trasplante Autólogo , Trasplante Homólogo , Cicatrización de HeridasRESUMEN
Central nervous system (CNS)-directed prophylactic intrathecal (IT) therapy is indicated in patients with Burkitt and acute lymphoblastic lymphoma. Its role in diffuse large B cell lymphoma (DLBCL), a heterogeneous subtype, is less well defined. While addition of rituximab to standard cyclophosphamide-hydroxydaunorubicin-oncovin-prednisone (CHOP) chemotherapy (R-CHOP) has improved the outcomes of DLBCL patients, its role in reducing CNS relapse is unclear. We aim to (1) evaluate the clinical risk factors predictive of CNS relapse, (2) the role of rituximab in influencing CNS relapse, and (3) role of intrathecal prophylaxis. Four hundred ninety-nine patients with DLBCL from 2000 to 2008 were included (CHOP 179 vs. R-CHOP 320). IT prophylaxis was administered to 82 patients based on our institution's guidelines. Baseline characteristics between CHOP- and R-CHOP-treated patients were similar. Although R-CHOP significantly increased the complete remission rate from 71% to 81% (P < 0.01), CNS relapse rates remained unchanged (R-CHOP 6% vs. CHOP 5.1%). On multivariate analysis, poor performance status (Eastern Cooperative Oncology Group >1; hazard ratio (HR) = 2.01, 95% confidence interval (CI) 1.29-3.14), failure to attain remission (non-complete response (CR) vs. CR: HR = 2.39, 95% CI = 1.03 to 5.51), testicular (HR = 6.67, 95% CI = 1.62 to 27.53), kidney (HR = 20.14, 95% CI = 5.23 to 77.46), and breast involvement (HR = 6.14, 95% CI = 1.61 to 23.37) were each independently predictive of CNS relapse. Use of IT prophylaxis did not appear to decrease CNS relapse. Median survival after CNS relapse was 3.2 months. CNS relapse, a fatal event, remains a challenge in R-CHOP-treated patients. IT prophylaxis may not be sufficient to reduce CNS relapse, and strategies including systemic agents with high CNS penetration should be evaluated in high-risk patients identified in this study.