Ardeshir Ghavamzadeh

BACKGROUND: A hot new topic in medical treatment is the use of mesenchymal stem cells (MSC) in therapy. The low frequency of this subpopulation of stem cells in bone marrow (BM) necessitates their in vitro expansion prior to clinical use. We evaluated the effect of long term culture on the senescence of these cells. RESULTS: The mean long term culture was 118 days and the mean passage number was 9. The average number of PD decreased from 7.7 to 1.2 in the 10th passage. The mean telomere length decreased from 9.19 Kbp to 8.7 kbp in the 9th passage. Differentiation potential dropped from the 6th passage on. The culture's morphological abnormalities were typical of the Hayflick model of cellular aging. CONCLUSION: We believe that MSC enter senescence almost undetectably from the moment of in vitro culturing. Simultaneously these cells are losing their stem cell characteristics. Therefore, it is much better to consider them for cell and gene therapy early on.

Background: The standard treatment for decompensated liver cirrhosis is liver transplantation. However, it has several limitations. Recent animal studies suggest that bone marrow stem cell transplantation can lead to regression of liver fibrosis. The objective of this study was to determine the safety and feasibility of autologous bone marrow-mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis. Methods: In this phase 1 trial, four patients with decompensated liver cirrhosis were included. Their bone marrow was aspirated, mesenchymal stem cells were cultured, and a mean 31.73 × 106 mesenchymal stem cells were infused through a peripheral vein. Primary outcomes were evaluating the safety and feasibility of the work. Secondary outcomes were evaluating changes in the model for end-stage liver disease score, and the quality of life of the patients. Results: There were no side-effects in the patients during follow-up. The model for end-stage liver disease scores of patients 1, and 4 improved by four and three points, respectively by the end of follow-up. Furthermore, the quality of life of all four patients improved by the end of follow-up. Using SF-36 questionnaire, the mean physical component scale increased from 31.44 to 65.19, and the mean mental component scale increased from 36.32 to 65.55. Conclusion: Mesenchymal stem cell transplantation seems to be feasible and safe in the treatment of decompensated liver cirrhosis. Background: The standard treatment for decompensated liver cirrhosis is liver transplantation. However, it has several limitations. Recent animal studies suggest that bone marrow stem cell transplantation can lead to regression of liver fibrosis. The objective of this study was to determine the safety and feasibility of autologous bone marrow-mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis. Methods: In this phase 1 trial, four patients with decompensated liver cirrhosis were included. Their bone marrow was aspirated, mesenchymal stem cells were cultured, and a mean 31.73 × 106 mesenchymal stem cells were infused through a peripheral vein. Primary outcomes were evaluating the safety and feasibility of the work. Secondary outcomes were evaluating changes in the model for end-stage liver disease score, and the quality of life of the patients. Results: There were no side-effects in the patients during follow-up. The model for end-stage liver disease scores of patients 1, and 4 improved by four and three points, respectively by the end of follow-up. Furthermore, the quality of life of all four patients improved by the end of follow-up. Using SF-36 questionnaire, the mean physical component scale increased from 31.44 to 65.19, and the mean mental component scale increased from 36.32 to 65.55. Conclusion: Mesenchymal stem cell transplantation seems to be feasible and safe in the treatment of decompensated liver cirrhosis.

We analyzed the outcomes of 485 patients with thalassemia major (TM) or sickle cell disease (SCD) receiving HLA-identical sibling cord blood transplantation (CBT, n = 96) or bone marrow transplantation (BMT, n = 389). Compared with patients given BMT, CBT recipients were significantly younger (median age 6 vs 8 years, P = .02), and were treated more recently (median year 2001 vs 1999, P < .01). A higher proportion of patients with TM belonging to classes II-III of the Pesaro classification received BMT (44%) compared with CBT (39%, P < .01). In comparison with patients receiving BMT (n = 259, TM; n = 130, SCD), those given CBT (n = 66, TM; n = 30, SCD) had slower neutrophil recovery, less acute graft-versus-host disease (GVHD) and none had extensive chronic GVHD. With a median follow-up of 70 months, the 6-year overall survival was 95% and 97% after BMT and CBT, respectively (P = .92). The 6-year disease-free survival (DFS) was 86% and 80% in TM patients after BMT and CBT, respectively, whereas DFS in SCD patients was 92% and 90%, respectively. The cell dose infused did not influence outcome of patients given CBT. In multivariate analysis, DFS did not differ between CBT and BMT recipients. Patients with TM or SCD have excellent outcomes after both HLA-identical sibling CBT and BMT.

BACKGROUND: Mesenchymal stem cells (MSCs) with their potential to differentiate into mesodermal and non-mesodermal lineages have several immunomodulatory characteristics. These properties make them promising tools in cell and gene therapy. OBJECTIVE: To evaluate the potential therapeutic applications of autologous MSC in improving clinical manifestations of MS patients. METHODS: Ten patients were included in this pilot study. All had progressive disease that had not responded to disease modifying agents including Mitoxantrone. Their Expanded Disability Status Scale (EDSS) score ranged from 3.5 to 6. Patients were injected intrathecally with culture expanded MSCs. They were followed with monthly neurological assessment and a MRI scan at the end of the first year. RESULTS: During 13 to 26 months of follow up (mean: 19 months), the EDSS of one patient improved from 5 to 2.5 score. Four patients showed no change in EDSS. Five patients' EDSS increased from 0.5 to 2.5. In the functional system assessment, six patients showed some degree of improvement in their sensory, pyramidal, and cerebellar functions. One showed no difference in clinical assessment and three deteriorated. The result of MRI assessment after 12 months was as following: seven patients with no difference, two showed an extra plaque, and one patient showed decrease in the number of plaques. CONCLUSION: This preliminary report emphasizes on the feasibility of autologous MSC for treatment of MS patients. However, in order to draw a definitive conclusion a larger sample size is required.