Abstract
The replacement of functional pancreatic β-cells is seen as an attractive potential therapy for diabetes, because diabetes results from an inadequate β-cell mass. Inducing replication of the remaining β-cells and new islet formation from progenitors within the pancreas (neogenesis) are the most direct ways to increase the β-cell mass. Stimulation of both replication and neogenesis have been reported in rodents, but their clinical significance must still be shown. Because human islet transplantation is limited by the scarcity of donors and graft failure within a few years, efforts have recently concentrated on the use of stem cells to replace the deficient β-cells. Currently, embryonic stem cells and induced pluripotent stem cells achieve high levels of β-cell differentiation, but their clinical use is still hampered by ethical issues and/or the risk of developing tumors after transplantation. Pancreatic epithelial cells (duct, acinar, or α-cells) represent an appealing alternative to stem cells because they demonstrate β-cell differentiation capacities. Yet translation of such capacity to human cells after significant in vitro expansion has yet to be achieved. Besides providing new β-cells, cell therapy also has to address the question on how to protect the transplanted cells from destruction by the immune system via either allo- or autoimmunity. Encouraging developments have been made in encapsulation and immunomodulation techniques, but many challenges still remain. Herein, we discuss recent advances in the search for β-cell replacement therapies, current strategies for circumventing the immune system, and mandatory steps for new techniques to be translated from bench to clinics.