Preclinical development of the Islet Sheet.
The Islet Sheet is a thin planar bioartificial endocrine pancreas fabricated by gelling highly purified alginate and islets of Langerhans. Acellular alginate layers form a uniform immunoprotective barrier to host rejection of the encapsulated cells, with the tissue nourished by passive diffusion from adjacent host tissue. The overall thickness of the Islet Sheet, 250 microm, is chosen to maximize nutrient diffusion. In this paper we describe the early development of the Islet Sheet, including purification and fractionation of the alginates used, difficulties in maintaining sheet planarity, and preliminary metabolic studies in pancreatectomized dogs. In a key experiment, approximately 75,000 allogeneic islet equivalents in six Islet Sheets were sutured to the omentum of a 7-kg female beagle dog at the time of pancreatectomy. Fasting euglycemia was maintained for 84 days. Fed blood sugars were usually below 150 mg/dL. A single injection of 2 U insulin was administered on day 9, and antibiotics were administered for two weeks. No other drugs were used. IVGTT post implant was not normal, but seemed to improve between 30 and 60 days. Upon omentectomy and sheet removal the metabolic parameters deteriorated to a frankly diabetic state within seven days. The sheets did not remain flat, but fragments were recovered within hard, mostly acellular capsules. Dithizone staining showed islets within alginate sheets recovered from the interior of these capsules, suggesting that allogeneic islet tissue survived 84 days and was responsible for maintaining fasting euglycemia.
Storrs
R
R
Islet Sheet Medical, LLC,San Francisco, California 94131, USA. Rick@isletmedical.com
Dorian
R
R
King
S R
SR
Lakey
J
J
Rilo
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D021522:Bioartificial Organs; D001786:Blood Glucose / Q000032:analysis; D004285:Dogs; D005260:Female; D005951:Glucose Tolerance Test; D007328:Insulin / Q000008:administration & dosage; D007515:Islets of Langerhans; D008567:Membranes, Artificial; D008855:Microscopy, Electron, Scanning; D019397:Pancreas, Artificial
D000900:Anti-Bacterial Agents; D001786:Blood Glucose; D007328:Insulin; D008567:Membranes, Artificial