title: Role of Tumor Necrosis Factor-Producing Mesenchymal Stem Cells on Apoptosis of Chronic B-lymphocytic Tumor Cells Resistant to Fludarabine-based Chemotherapy.
abstract: BACKGROUND
  B-cell chronic lymphocytic leukemia B (B-CLL), the most common type of leukemia, may be caused by apoptosis deficiency in the body. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) as providers of pro-apoptotic molecules such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), can be considered as an effective anti-cancer therapy candidate. Therefore, in this study we assessed the role of tumor necrosis factor-producing mesenchymal stem cells oin apoptosis of B-CLL cells resistant to fludarabine- based chemotherapy.
  
  
  METHODS
  In this study, after isolation and culture of AD-MSCs, a lentiviral LeGO-iG2-TRAIL-GFP vector containing a gene producing the ligand pro-apoptotic with plasmid PsPAX2 and PMDG2 virus were transfected into cell-lines to generate T293HEK. Then, T293HEK cell supernatant containing the virus produced after 48 and 72 hours was collected, and these viruses were transduced to reprogram AD-MSCs. Apoptosis rates were separately studied in four groups: group 1, AD-MSCs-TRAIL; group 2, AD-MSCs-GFP; group 3, AD-MSCs; and group 4, CLL.
  
  
  RESULTS
  Observed apoptosis rates were: group 1, 42 ± 1.04%; group 2, 21 ± 0.57%; group 3, 19± 2.6%; and group 4, % 0.01 ± 0.01. The highest rate of apoptosis thus occurred ingroup 1 (transduced TRAIL encoding vector). In this group, the average medium-soluble TRAIL was 72.7pg/m and flow cytometry analysis showed a pro-apoptosis rate of 63 ± 1.6%, which was again higher than in other groups.
  
  
  CONCLUSIONS
  In this study we have shown that tumor necrosis factor (TNF) secreted by AD-MSCs may play an effective role in inducing B-CLL cell apoptosis.
authors.affiliation: Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran E-mail : ghasemsaki@yahoo.com.
authors.forename: Armita
authors.initials: A
authors.lastname: Valizadeh
authors.forename: Ahmad
authors.initials: A
authors.lastname: Ahmadzadeh
authors.forename: Ghasem
authors.initials: G
authors.lastname: Saki
authors.forename: Ali
authors.initials: A
authors.lastname: Khodadadi
authors.forename: Ali
authors.initials: A
authors.lastname: Teimoori
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002478:Cells, Cultured; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha; D014740:Vidarabine; C024352:fludarabine