title: Mesenchymal stem cells as vehicles for targeted delivery of anti-angiogenic protein to solid tumors.
abstract: BACKGROUND
  Inhibition of tumor-induced angiogenesis may restrict tumor growth and metastasis. Long-term systemic delivery of angiogenic inhibitors is associated with toxicity, as well as other severe side-effects. The utility of cells as vehicles for gene therapy to deliver therapeutic molecules has been suggested to represent an efficient approach. Mesenchymal stem cells (MSCs) exhibit a tropism to cancer tissue, and may serve as a cellular delivery vehicle and a local producer of anti-angiogenic agents.
  
  
  METHODS
  In the present study, we attempted to assess production of the transgene, α1-antitrypsin (AAT), in lentivirus-transduced human MSCs and its cytotoxicity against human umbilical cord vein endothelial cells (HUVEC). The secreted protein from these effector cells was determined by an enzyme-linked immunosorbent assay. The cytotoxicity of hMSCs that overexpress the human AAT gene against HUVEC was evaluated with an apoptotic assay.
  
  
  RESULTS
  Lentivirus-transduced hMSCs produced functional AAT and displayed much higher cytotoxicity against HUVEC than untransduced hMSCs. Moreover, AAT secreted from transduced hMSCs significantly inhibited HUVEC proliferation compared to untransduced hMSCs. The data obtained demonstrate for the first time that genetically modified hMSCs released abundant and functional AAT that caused obvious cytotoxicity to HUVEC.
  
  
  CONCLUSIONS
  hMSC may serve as an effective platform for the targeted delivery of therapeutic proteins to cancer sites.
authors: Department of Internal Medicine, Transplant Research Program, University of California, Davis Medical Center, Sacramento, CA 95817, USA.
authors: Mahboobe
authors: M
authors: Ghaedi
authors: Masoud
authors: M
authors: Soleimani
authors: Narges Mohammad
authors: NM
authors: Taghvaie
authors: Mahmood
authors: M
authors: Sheikhfatollahi
authors: Keyhan
authors: K
authors: Azadmanesh
authors: Abbas S
authors: AS
authors: Lotfi
authors: Jian
authors: J
authors: Wu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics; D014361:Trypsin Inhibitors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D014471:Umbilical Veins; D000515:alpha 1-Antitrypsin / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; D014361:Trypsin Inhibitors; D000515:alpha 1-Antitrypsin; D049452:Green Fluorescent Proteins; D010196:Pancreatic Elastase