Composite pancreatic organoids for the treatment of insulin-dependent diabetes
4th International Conference and Exhibition on Cell & Gene Therapy
August 10-12, 2015 London, UK

Henry E Young1, Frank Lochner2, George McCommon3, Lee Anne Cope4 and Asa C Black5

Posters-Accepted Abstracts: J Stem Cell Res Ther

Abstract:

Hypothesis: Decellularized pancreatic matrices seeded with endogenous stem cells and donor islets comprise an organoid
that demonstrates enhanced insulin secretion in response to a glucose challenge. The adult animals were euthanized
following the guidelines of Fort Valley State University-IACUC and Mercer University-IACUC. Adult porcine pancreases
were decellularized using a mixture of detergents. Adult rat pancreatic islets were obtained by lipase digestion followed by
Ficoll gradient separation. Control cultures consisted of decellularized matrices, naïve endogenous stem cells, and rat islets, all
cultured individually. Experimental groups consisted of islets co-cultured with clonal populations of pluripotent and totipotent
stem cells seeded on decellularized pancreatic matrices. Control and experimental cultures were challenged with the insulin
secretagogue glucose. The control and culture media were removed and stored at -20oC until assayed using a RIA specific
for rat insulin. The culture media, containing bovine insulin, were assayed using a RIA specific for rat insulin. No detectable
levels of insulin (bovine, rat, human, or porcine) were noted in controls of the media only, the stem cell populations or the
decellularized matrices, respectively. Native pancreatic islets secreted nanogram quantities of rat insulin per nanogram of
DNA. Composite pancreatic rat organoids demonstrated increased rat insulin secretion in the range of milligram quantities of
insulin per nanogram of DNA, i.e., a 250-fold increase in insulin secretion compared to pancreatic islets alone. These studies
suggest that composites of native islets, decellularized pancreatic matrices and endogenous pluripotent and totipotent stem
cells could provide enhanced secretory tissue for pancreatic islet transplants than donor islets alone.