Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

Proc Natl Acad Sci U S A. 2005 May 31;102(22):7964-9. doi: 10.1073/pnas.0405277102. Epub 2005 May 17.

Abstract

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Animals
  • Cell Differentiation*
  • Cells, Cultured
  • DNA Primers
  • Diabetes Mellitus, Type 1 / therapy*
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Genetic Engineering*
  • Genetic Therapy / methods*
  • Glucose / metabolism
  • Hepatocytes / cytology*
  • Hepatocytes / transplantation
  • Hepatocytes / ultrastructure
  • Homeodomain Proteins / genetics*
  • Humans
  • Immunohistochemistry
  • Insulin / metabolism
  • Islets of Langerhans / cytology*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Microscopy, Electron
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / genetics*
  • Transduction, Genetic / methods

Substances

  • DNA Primers
  • Homeodomain Proteins
  • Insulin
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • Glucose