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

Biomaterials. 2013 May;34(16):4002-4012. doi: 10.1016/j.biomaterials.2013.02.026. Epub 2013 Feb 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis
  • Animals
  • Cell Aggregation
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy*
  • Drug Compounding
  • Fetus / cytology*
  • Fluorescent Antibody Technique
  • Hepatocytes / cytology*
  • Hepatocytes / transplantation*
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Liver / cytology
  • Liver / embryology*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Multipotent Stem Cells / cytology
  • Neurogenesis
  • Osteogenesis
  • Phenotype
  • Stem Cell Factor / metabolism

Substances

  • Insulin
  • Stem Cell Factor