Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells
Authors: Tamar Blumenfeld
Iris Barshack
Tamar Sapir
Eytan Mor
Avraham Karasik
Sylvie Polak-Charcon
Smadar Eventov-Friedman
Irit Meivar-Levy
Sarah Pri-Chen
Keren Shternhall
Iris Goldberg
Ilan Shimon
Sarah Ferber
Hamutal Cohen
Lya Ben-Dor
Ehud Skutelsky
Journal: Proceedings of the National Academy of Sciences of the United States of America (2005)
Discipline: Multidisciplinary
Keywords: tissue availability; cell-replacement therapy; diabetic patients; adult human liver; beta-cell-replacement therapy
Affiliations: The Endocrine Institute, The Institute for Pathology, and The Maurice and Gabriela Goldschleger Eye Research Institute, Sheba Medical Center, Tel-Hashomer 52621, Israel.

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. 

Retracted: No

PubPeer comments:
 Supplemental Fig. 9a u2013 possible duplication. Could the authors check? ![file] , 
 #1 Thank you for bringing this my attention. I have contacted my colleague Scott Manalis (who is the corresponding author) and learned that indeed the wrong blot was inadvertently included when they assembled the final figure. We will work with the journal to correct this figure. , 
 #1 We appreciate that you have brought this to our attention. This is indeed an error on our part where the immunoblot for the -Gln condition of p-PKA-Calpha is a duplicate image of the -Glc condition. Fortunately, we have the original immunoblot data file which enabled us to extract the correct immumoblot for the -Gln condition. u00a0The corrected immunoblot closely resembles the duplicated one and so all conclusions from this figure remain unchanged. We will soon submit an Author Correction to Scientific Reports, which will include the correct version of Supplementary Figure 9a that I have included below: ![file] , 
 Correction to: Scientific Reports https: doi.org 10.1038 srep17401 This Article contains an error. In Supplemental Figure 9A, the immunoblot of P-PKA-Cu03b1 following glutamine depletion was inadvertently duplicated from the immunoblot of P-PKA-Cu03b1 following glucose depletion. The correct Supplementary Figure 9 appears below as Figure 1. https: www.nature.com articles s41598-020-69376-2 ,