Human pancreatic progenitors : implications for clinical transplantation in diabetes

Shortage in the number of available pancreas and isolated islets has forced researchers to study and develop different cell types that can be potentially used for cell replacement therapy in diabetes. The major question is the choice of such a cell type. Ideally, an islet progenitor cell should meet two criteria: (1) ability to proliferate while retaining its stem-cell properties under defined conditions, in vitro, and (2) to be able to efficiently differentiate into insulin-producing cells that can release physiologically significant amount of insulin in response to glucose. Although cell types such as embryonic stem cells satisfy the former criteria, none of the studies carried out until now have been able to meet the latter criteria. We proposed earlier that precursor/progenitor cells generated from human insulin-producing islet of Langerhans would be ideal candidates for clinical use in diabetes. One of the major reasons to propose this hypothesis is that epigenetic marks that characterize insulin promoter region in these islet cells are heritable and are retained in proliferating progenitor cells obtained from islets. There is now a significant amount of data to believe that human pancreatic islet-derived cells are better progenitors for differentiation into insulin-producing cells. In this chapter, we discuss the major cell types that have been proposed and assessed for potential use in cell replacement therapy for diabetes. Understanding the potential and safety of such cell types will help in considering their suitability for clinical use in diabetes.