Cell-Based Therapies for Diabetes: Progress towards a Transplantable Human β Cell Line

• Published in: Annals of the New York Academy of Sciences 2003-11, Vol.1005 (1), p.138-147
• Main Authors: ITKIN-ANSARI, PAMELA, GERON, IFAT, HAO, ERGENG, DEMETERCO, CARLA, TYRBERG, BJORN, LEVINE, FRED
• Format: Article
• Language: English
• Subjects: Base Sequence; Cell Line; diabetes; Diabetes Mellitus - therapy; DNA Primers; Humans; islets; Islets of Langerhans Transplantation; pancreas; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells; therapy; transplantation; β cell; βlox5
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1196/annals.1288.015

: Achieving normoglycemia is the goal of diabetes therapy. Potentially, there are many ways to achieve this goal, including transplantation of cells exhibiting glucose‐responsive insulin secretion. However, to be applicable to the large number of people who might benefit from β cell replacement, an unlimited supply of β cells must be found. To address this problem, we have been developing cell lines from the human endocrine pancreas. In one case, a cell line, βlox5, has been developed from human islets that can be induced under some circumstances to differentiate into functional β cells exhibiting appropriate glucose‐responsive insulin secretion. Inducing differentiation is complex, requiring the activation of multiple signaling pathways, including those downstream of those involved in cell‐cell contact and the glucagon‐like peptide‐1 receptor. In addition, transfer of the PDX‐1 gene is also necessary to render the cells competent for differentiation. However, it is clear that many other genes are involved in maintaining the commitment of βlox5 cells towards the β cell lineage. Understanding the complement of genes required to establish and maintain a β cell lineage commitment would be enormously helpful in efforts to develop a cell line that can be used for β cell replacement therapies. Here, we provide further information on the characteristics of cell lines that we have developed from the human pancreas that are relevant to the development of a β cell replacement therapy for diabetes.