title: Safety and efficacy of ethylenediaminetetraacetic acid for removing microcapsules.
abstract: BACKGROUND
  Microencapsulated islets are used to prevent immune rejection associated with pancreatic islet transplantation, but cellular overgrowth affects transplantation success, necessitating removal of microcapsules prior to retransplantation. This study aimed to investigate the safety and efficacy of ethylendiaminetetraacetic acid (EDTA) for the removal of microcapsules surrounding islet cells.
  
  
  METHODS
  Microcapsule dissolution was investigated after in vitro exposure to EDTA for 72 h. Dissolution, blood biochemical markers, and pathologic changes in abdominal organs were observed after intraperitoneal administration of different concentrations of EDTA to rats with abdominally transplanted empty microcapsules. The extent of overgrowth and time to adhesion development were recorded after implantation of microencapsulated islets into the abdominal cavity of diabetic rats. EDTA (0-240 mmol/L) was injected to observe the transplantation effect and ability to dissolve microcapsules.
  
  
  RESULTS
  There was a positive correlation between the rate of microcapsule dissolution and EDTA concentration in vitro. Following administration of 60 mmol/L EDTA, the majority of microcapsules within the abdominal cavity were dissolved and the retrieval rate was 2.6%. No adverse effects, abnormal blood biochemical markers, or organ damage were observed in rats 1 mo following intraperitoneal injection with EDTA at doses up to 60 mmol/L. Microcapsule retrieval and blood glucose were significantly higher in cases of grade II cellular overgrowth than in cases of grade 0-I overgrowth.
  
  
  CONCLUSIONS
  EDTA (60 mmol/L) dissolved microcapsules in vivo without affecting islet cell viability or secretion capacity, and without affecting blood biochemical markers. Optimal dissolution was achieved with grade 0-I overgrowth after implantation of microencapsulated islets.
authors: Department of Thyroid and Breast Diseases, Central Laboratory, Cell Transplantation Key Lab attached to Ministry of Public Health, and The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Ming
authors: M
authors: Ren
authors: Rui
authors: R
authors: Liu
authors: Bingjie
authors: B
authors: Lv
authors: Qingkun
authors: Q
authors: Gao
authors: Jing
authors: J
authors: Feng
authors: Yan
authors: Y
authors: Wu
authors: Zhiming
authors: Z
authors: Zhao
authors: Yi
authors: Y
authors: Zhou
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001464:Barium / Q000737:chemistry*; D015415:Biomarkers / Q000097:blood; D002214:Capsules / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D004492:Edetic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D005355:Fibrosis; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007274:Injections, Intraperitoneal; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D008297:Male; D008422:Materials Testing; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D000464:Alginates; D015415:Biomarkers; D002214:Capsules; D006603:Hexuronic Acids; D001464:Barium; D020723:Glucuronic Acid; D004492:Edetic Acid