Insulin-Producing Cells from Tissue Stem/Progenitor Cells: Are Autologous Cells Preferable to Allogeneic?

Article View

The Review of Diabetic Studies,2005,2,1,6-8.
Published:May 2005
Author(s) affiliations:

Shimon Efrat

Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, 69978 Israel.


Type 1 diabetes is caused by autoimmune destructtion of the pancreatic islet insulin-producing β- cells. Insulin administration does not prevent longterm complications of the disease, since the optimal insulin dosage is difficult to adjust. Replacement of the damaged cells with regulated insulin-producing cells is considered as the ultimate cure for type 1 diabetes. Transplantation of intact human pancreas or isolated islets has been severely limited by the scarcity of human tissue donors, and the search is on for an abundant source of human insulin-producing cells. Isolated human islets have been difficult to expand in tissue culture without partial or complete loss of function. Recent progress in stem cell biology has fanned hopes for the generation of regulated insulin-producing cells by differentiation from various sources of stem/progenitor cells. There are 2 major types of stem cells: embryonic stem (ES) cells, and tissue-derived stem cells. ES cells are pluripotent cells which can be easily propagated in tissue culture. Their spontaneous differentiation in vitro generates, among many cell types, a small percentage of insulin-producing cells [1, 2]. However, despite efforts to isolate these differentiated cells [3, 4], or stimulate their generation by various protocols [5], evidence is still lacking in support of their efficacy and safety in experimental models. A second type of stem cells resides in fetal and adult tissues and is responsible for tissue maintenance throughout life. These are more restricted than ES cells in their replication and multilineage differentiation capacities. However, recent reports have suggested that adult tissue stem cells can give rise to cell types from other tissues, including insulin- producing cells [6-8], given appropriate stimuli. Although findings on the physiological plasticity of tissue stem cells remain controversial, it has been clearly demonstrated that cells from tissues such as liver and intestine can be reprogrammed to assume a β-like phenotype by expression of dominant β-cell transcription factor genes [9-13]. In contrast to ES cells, tissue stem cells offer the possibility of employing autologous cells, either as a biopsy to be manipulated ex vivo and then transplanted into each patient, or by in vivo targeting of genes or differentiation factors. This possibility calls for an evaluation of the relative advantages of autologous versus allogeneic tissues in cell engineering strategies for cell replacement therapy of type 1 diabetes. Read more...