Treatment of diabetes mellitus with microencapsulated fetal human liver (FH-B-TPN) engineered cells.

Abstract

Transplantation of whole human pancreases or isolated islets into patients with type 1 diabetes mellitus has been severely hampered by the scarcity of cadaveric human donor organs, which mandates search for insulin producing cells/tissue source alternatives. Recent progress in stem cell biology has started looking into functionally competent, insulin-secreting progenitor cells. It had been previously observed that induced expression of the β-cell transcriptional factor of the pancreatic and duodenal homeobox gene1 (PDX1), in human hepatocytes, may activate multiple features of the β-cell phenotype. These "FH-B-TPN" cells were shown to release insulin in response to physiological glucose stimulation both, in vitro and in vivo. However, because FH-B-TPNs lack the expression of a number of β-cell or non β-cell genes, and are associated with low insulin content, we aimed to determine whether these cells, upon physical manipulation and envelopment within "clinical grade" alginate-based microcapsules, would reverse hyperglycemia after graft into diabetic animal models.