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Cell-Based Therapies for Diabetes: Progress towards a Transplantable Human ß Cell Line
Cancer Center, University of California, San Diego, La Jolla, California, USA
Address for correspondence: Dr. Fred Levine, Cancer Center, UCSD School of Medicine-0912, La Jolla, CA 92093-0912. Voice: 858-822-2039; fax: 858-822-4181. flevine{at}ucsd.edu Ann. N.Y. Acad. Sci. 1005: 138-147 (2003).
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 ß cell replacement, an unlimited supply of ß 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, ßlox5, has been developed from human islets that can be induced under some circumstances to differentiate into functional ß 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 ßlox5 cells towards the ß cell lineage. Understanding the complement of genes required to establish and maintain a ß cell lineage commitment would be enormously helpful in efforts to develop a cell line that can be used for ß 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 ß cell replacement therapy for diabetes.
Key Words: ß cell • ßlox5 • diabetes • islets • pancreas • therapy • transplantation This article has been cited by other articles:
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