title: Clinical porcine islet xenotransplantation under comprehensive regulation.
abstract: BACKGROUND
  Xenotransplantation with porcine islets is a promising approach to overcome the shortage of human donors. This is the first report of phase 1/2a xenotransplantation study of encapsulated neonatal porcine islets under the current framework of regulations for xenotransplantation in New Zealand.
  
  
  METHODS
  Newborn piglets were anesthetized and bled, and the pancreata were removed with the use of sterile technique and processed. Encapsulated neonatal porcine islets were implanted with the use of laparoscopy into the peritoneal cavity of 14 patients with unstable type 1 diabetes without any immunosuppressive drugs. The patients received encapsulated islets of 5,000 (n = 4; group 1), 10,000 (n = 4; group 2), 15,000 (n = 4; group 3), or 20,000 (n = 2; group 4) islet equivalents per kg body weight. Outcome was determined from adverse event reports, HbA1c, total daily insulin dose, and frequency of unaware hypoglycemic events. To assess graft function, transplant estimated function (TEF) scores were calculated. Sufficient or marginal numbers of encapsulated neonatal porcine islets were transplanted into streptozotocin-induced diabetic B6 mice as an in vivo functional assay.
  
  
  RESULTS
  There were 4 serious adverse events, of which 3 were considered to be possibly related to the procedure. Tests for porcine endogenous retrovirus DNA and RNA were all negative. The numbers of unaware hypoglycemia events were reduced after transplantation in all groups. Four of 14 patients attained HbA1c <7% compared with 1 at baseline. The average TEF scores were 0.17, 0.02, -0.01, and 0.08 in groups 1, 2, 3, and 4 respectively. The in vivo study demonstrated that a sufficient number of the transplanted group reversed diabetes with positive porcine C-peptide.
  
  
  CONCLUSIONS
  Transplantation of encapsulated neonatal porcine islets was safe and was followed by a reduction in unaware hypoglycemia events in unstable type 1 diabetic patients. The mouse in vivo assessment data demonstrated certain graft function.
authors.affiliation: Otsuka Pharmaceutical Factory, Naruto, Japan. Electronic address: matsumoto.shinichi@otsuka.jp.
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Living Cell Technologies, Auckland, New Zealand.
authors.forename: P
authors.initials: P
authors.lastname: Tan
authors.affiliation: Centre for Clinical Research and Effective Practice, Middlemore Hospital, Auckland, New Zealand.
authors.forename: J
authors.initials: J
authors.lastname: Baker
authors.affiliation: Living Cell Technologies, Auckland, New Zealand.
authors.forename: K
authors.initials: K
authors.lastname: Durbin
authors.affiliation: Otsuka Pharmaceutical Factory, Naruto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tomiya
authors.affiliation: Otsuka Pharmaceutical Factory, Naruto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Otsuka Pharmaceutical Factory, Naruto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Doi
authors.affiliation: Living Cell Technologies, Auckland, New Zealand.
authors.forename: R B
authors.initials: RB
authors.lastname: Elliott
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002096:C-Peptide / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy / Q000601:surgery*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009520:New Zealand; D013552:Swine; D014183:Transplantation, Heterologous / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin