Abstract
Recent scientific breakthroughs in stem cell biology suggest that a sustainable treatment approach to cure diabetes mellitus (DM) can be achieved in the near future. However, the transplantation complexities and the difficulty in obtaining the stem cells from adult cells of pancreas, liver, bone morrow and other cells is a major concern. The epoch-making strategy of transcription-factor based cellular reprogramming suggest that these barriers could be overcome, and it is possible to reprogram any cells into functional β cells. Contemporary biological and analytical techniques help us to predict the key transcription factors needed for β-cell regeneration. These β cell-specific transcription factors could be modulated with diverse reprogramming protocols. Among cellular reprogramming strategies, small molecule approach gets proclaimed to have better clinical prospects because it does not involve genetic manipulation. Several small molecules targeting certain epigenetic enzymes and/or signaling pathways have been successful in helping to induce pancreatic β-cell specification. Recently, a synthetic DNA-based small molecule triggered targeted transcriptional activation of pancreas-related genes to suggest the possibility of achieving desired cellular phenotype in a precise mode. Here, we give a brief overview of treating DM by regenerating pancreatic β-cells from various cell sources. Through a comprehensive overview of the available transcription factors, small molecules and reprogramming strategies available for pancreatic β-cell regeneration, this review compiles the current progress made towards the generation of clinically relevant insulin-producing β-cells.
Highlights
Diabetes mellitus (DM) is an endocrine disorder associated with hyperglycemia and results in severe damage to the blood vessels, eyes, kidneys and heart
We provide a critical overview of the strategies available for pancreatic β cell regeneration and list some of the well-known and recently identified transcription factors
In general, diseases are characterized by dysregulation in the transcriptional machinery, which is responsible for the maintenance of the cellular homeostasis [78]
Summary
Diabetes mellitus (DM) is an endocrine disorder associated with hyperglycemia and results in severe damage to the blood vessels, eyes, kidneys and heart. This innovative approach overcame the barrier of immune rejection and could aid in identifying the genomic aberrations associated with T1DM These patient-derived iPS cells (termed DiPS) expressed and stained positive for some of the pancreatic endocrine markers including insulin, PDX1, NKX2-2, glucagon and somatostatin. It is possible to generate human pancreatic endoderm and differentiate them in vivo into glucose responsive mature islet cell types capable of secreting C-peptide, insulin, glucagon, or somatostatin. A SAHA-PIP called K got categorized as the first-ever small molecule capable of enforcing transcriptional activation of meiosis-regulating germ cell genes in a human somatic cell [75]. CD24 (cluster of differentiation 24) is a cell adhesion molecule and a recent study revealed CD24 as a marker for PDX1-positive pancreatic progenitors derived from human ESCs [77]. Reprogrammed cells with fewer factors should have better clinical prospects and could facilitate the achievement of homogenous insulin producing cells, which is a major bottleneck that hampers the clinical translation of artificially reprogrammed cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
