A survey on cellular and engineered tissue therapies in Europe in 2008

Cellular therapy is an evolving investigational treatment modality in regenerative medicine, but little published information is available on its current use. Starting from the established European group for Blood and Marrow Transplantation activity survey on hematopoietic stem cell transplantation, a joint committee of four major scientific organizations made a coordinated attempt to collect detailed information in Europe for the year 2008. Thirty-three teams from 16 countries reported data on 656 patients to a "novel cellular therapy" survey, which were combined to additional 384 records reported to the standard European group for Blood and Marrow Transplantation survey. Indications were cardiovascular (29%; 100% autologous), musculoskeletal (18%; 97% autologous), neurological (9%; 39% autologous), epithelial/parenchymal (9%; 18% autologous), autoimmune diseases (12%; 77% autologous), or graft-versus-host disease (23%; 13% autologous). Reported cell types were hematopoietic stem cells (39%), mesenchymal stromal cells (47%), chondrocytes (5%), keratinocytes (7%), myoblasts (2%), and others (1%). In 51% of the grafts, cells were delivered after expansion; in 4% of the cases, cells were transduced. Cells were delivered intravenously (31%), intraorgan (45%), on a membrane or gel (14%), or using three-dimensional scaffolds (10%). This data collection platform is expected to capture and foresee trends for novel cellular therapies in Europe, and warrants further consolidation and extension

Haematopoietic stem cell transplantation for poor-prognosis systemic sclerosis

Haematopoietic stem cell transplantation (HSCT) following intensive immune suppression has been used in >2000 patients with severe autoimmune diseases for 18 years, including 300 with SSc. The concept is to profoundly reduce the bulk of auto-aggressive immune competent cells and then rescue the patient's ablated haematopoiesis via an autologous HSCT. An early analysis of uncontrolled phase I/II data suggested that approximately one-third of these achieved a substantial improvement, with a relapse rate of 25% and a treatment-related mortality ranging from 6% to 23% across different studies. These early results led to three prospective randomized controlled trials, two of which are completed, confirming that HSCT shows clear advantages over conventional immunosuppression, but with significant toxicity. In some patients, sustained complete normalization of skin changes, reversal of positive autoantibody status and withdrawal of immunosuppressive medication were observed. These results attest to the profound effects of HSC

Cell therapy for autoimmune diseases

Cell therapy, pioneered for the treatment of malignancies in the form of bone marrow transplantation, has subsequently been tested and successfully employed in autoimmune diseases. Autologous haemopoietic stem cell transplantation (HSCT) has become a curative option for conditions with very poor prognosis such as severe forms of scleroderma, multiple sclerosis, and lupus, in which targeted therapies have little or no effect. The refinement of the conditioning regimens has virtually eliminated transplant-related mortality, thus making HSCT a relatively safe choice. Although HSCT remains a nonspecific approach, the knowledge gained in this field has led to the identification of new avenues. In fact, it has become evident that the therapeutic efficacy of HSCT cannot merely be the consequence of a high-dose immuno-suppression, but rather the result of a resetting of the abnormal immune regulation underlying autoimmune conditions. The identification of professional and nonprofessional immunosuppressive cells and their biological properties is generating a huge interest for their clinical exploitation. Regulatory T cells, found abnormal in several autoimmune diseases, have been proposed as central to achieve long-term remissions. Mesenchymal stem cells of bone marrow origin have more recently been shown not only to be able to differentiate into multiple tissues, but also to exert a potent antiproliferative effect that results in the inhibition of immune responses and prolonged survival of haemopoietic stem cells. All of these potential resources clearly need to be investigated at the preclinical level but support a great deal of enthusiasm for cell therapy of autoimmune diseases

The value of [18F]FDG-PET in the diagnosis of large-vessel vasculitis and the assessment of activity and extent of disease

Purpose: This study was performed to investigate the value of 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) in the diagnosis of large-vessel vasculitis and the assessment of activity and extent of disease. Methods: Twenty-six consecutive patients (21 females, 5 males; median age -years, range 17-86years) with giant cell arteritis or Takayasu's arteritis were examined with [18F]FDG-PET. Follow-up scans were performed in four patients. Twenty-six age- and gender-matched controls (21 females, 5 males; median age 71years, range 17-86years) were included. The severity of large-vessel [18F]FDG uptake was visually graded using a four-point scale. C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured and correlated with [18F]FDG-PET results by logistic regression. Results: [18F]FDG-PET revealed pathological findings in 18 of 26 patients. Three scans were categorised as grade I, 12 as grade II and 3 as grade III arteritis. Visual grade was significantly correlated with both CRP and ESR levels (p=0.002 and 0.007 respectively; grade I: CRP 4.0mg/l, ESR 6mm/h; grade II: CRP 37mg/l, ESR 46mm/h; grade III: CRP 172mg/l, ESR 90mm/h). Overall sensitivity was 60% (95% CI 40.6-77.3%), specificity 99.8% (95% CI 89.1-100%), positive predictive value 99.7% (95% CI 77-100%), negative predictive value 67.9% (95% CI 49.8-80.9%) and accuracy 78.6% (95% CI 65.6-88.4%). In patients presenting with a CRP <12mg/l or an ESR <12mm/h, logistic regression revealed a sensitivity of less than 50%. In patients with high CRP/ESR levels, sensitivity was 95.5%/80.7%. Conclusion: [18F]FDG-PET is highly effective in assessing the activity and the extent of large-vessel vasculitis. Visual grading was validated as representing the severity of inflammation. Its use is simple and provides high specificity, while high sensitivity is achieved by scanning in the state of active inflammatio

Immunomodulatory properties of mesenchymal stem cells : a review based on an interdisciplinary meeting held at the Kennedy Institute of Rheumatology Division, London, UK, 31 October 2005

Peer reviewedPublisher PD

Late-onset systemic sclerosis—a systematic survey of the EULAR scleroderma trials and research group database

Objective. The clinical course of SSc depends on subtype, organ involvement and age. Few data are reported on patients suffering from late-onset SSc. Methods. We analysed data from 8554 patients prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) group database. Late-onset SSc was defined as onset of non-RP disease features at or beyond 75 years of age. Disease characteristics, clinical features, disease course and mortality were evaluated. Results. A total of 123 patients with SSc onset at or beyond 75 years of age were identified. Compared with patients <75 years they had more frequently limited than diffuse SSc and a higher prevalence of anti-centromere autoantibodies. Fewer old patients had digital ulcers. The modified Rodnan's skin score, the prevalence of lung fibrosis and renal crisis did not differ significantly between groups. Pulmonary hypertension (PH) measured by echocardiography was more prevalent in the late-onset group, as well as arterial hypertension and diastolic dysfunction. Late-onset SSc remained a positive predictor for PH in multivariate analyses. No significant difference of the two groups in skin score or diffusion capacity was observed during follow-up. Mortality due to SSc was higher in the late-onset group, but the survival time from diagnosis was longer compared with the younger patients. Conclusion. Late-onset SSc shows a distinct clinical presentation and outcome. Patients with late-onset SSc suffer more frequently from the limited subtype and PH, but fewer patients have digital ulcers. PH may in part be determined by underlying cardiovascular diseas