Lineage Reprogramming: A Promising Road for Pancreatic β Cell Regeneration

Readily available cells, such as fibroblasts and blood cells, might be used for in vitro reprogramming into β cells in patient-specific transplantation. In vivo β cell reprogramming will potentially be an important strategy for β cell regeneration. At present, the leading cell contenders for successful therapeutic transformation into β cells appear to be pancreatic endocrine α cells, exocrine acinar cells, and enteroendocrine cells. For instructive strategies, complete small molecule-based reprogramming independent of gene manipulations will need to be extensively investigated with the goal to obtain fully functional β cells for clinical application. Cell replacement therapy is a promising method to restore pancreatic β cell function and cure diabetes. Distantly related cells (fibroblasts, keratinocytes, and muscle cells) and developmentally related cells (hepatocytes, gastrointestinal, and pancreatic exocrine cells) have been successfully reprogrammed into β cells in vitro and in vivo. However, while some reprogrammed β cells bear similarities to bona fide β cells, others do not develop into fully functional β cells. Here we review various strategies currently used for β cell reprogramming, including ectopic expression of specific transcription factors associated with islet development, repression of maintenance factors of host cells, regulation of epigenetic modifications, and microenvironmental changes. Development of simple and efficient reprogramming methods is a key priority for developing fully functional β cells suitable for cell replacement therapy. Cell replacement therapy is a promising method to restore pancreatic β cell function and cure diabetes. Distantly related cells (fibroblasts, keratinocytes, and muscle cells) and developmentally related cells (hepatocytes, gastrointestinal, and pancreatic exocrine cells) have been successfully reprogrammed into β cells in vitro and in vivo. However, while some reprogrammed β cells bear similarities to bona fide β cells, others do not develop into fully functional β cells. Here we review various strategies currently used for β cell reprogramming, including ectopic expression of specific transcription factors associated with islet development, repression of maintenance factors of host cells, regulation of epigenetic modifications, and microenvironmental changes. Development of simple and efficient reprogramming methods is a key priority for developing fully functional β cells suitable for cell replacement therapy. in embryogenesis, development depends on the accurate execution of differentiation programs through which a particular cell (or embryo) adopts specific cell fates. The cell fate determination can be divided into two states: the cell can be committed (specified) or determined. In the committed state, a certain fate can be reversed or transformed to another fate. If a cell is in a determined state, the cell is fixed in a specific fate and undergoes differentiation, which brings about actual changes in structure, function, and biochemistry. All these events result in the development of specific cell types. cells are injected into a patient to replace the original cells; these cells are used in the treatment of degenerative diseases. cells that are derived from the inner cell mass of mammalian blastocysts. They have the ability to grow indefinitely while maintaining pluripotency. In addition, they are able to differentiate into cells of all three germ layers. heritable alterations that do not involve changes in the DNA sequence but rather represent covalent modifications such as DNA methylation and histone modifications that alter DNA accessibility and chromatin structure, thereby resulting in selective gene expression or repression. first established by the Yamanaka group, they are pluripotent cells, similar to ESCs. iPSCs can be derived from differentiated cells by transfecting pluripotent factors or by adding cytokines, epigenetic regulators, and small molecules. cells with the capacity to undergo self-renewal and lineage differentiation. According to their developmental potential, stem cells can be divided into different categories: totipotent, pluripotent, multipotent, and unipotent. one of the most commonly used substances to induce diabetes in rodents. STZ can selectively destroy rodent islet β cells by entering the β cells via a glucose transporter, Glut2. STZ induces DNA damage and oxidative stress, which leads to β cell necrosis.