Abstract
Diabetes is a metabolic disease which affects not only glucose metabolism but also lipid and protein metabolism. It encompasses two major types: type 1 and 2 diabetes. Despite the different etiologies of type 1 and 2 diabetes mellitus (T1DM and T2DM, respectively), the defining features of the two forms are insulin deficiency and resistance, respectively. Stem cell therapy is an efficient method for the treatment of diabetes, which can be achieved by differentiating pancreatic β-like cells. The consistent generation of glucose-responsive insulin releasing cells remains challenging. In this review article, we present basic concepts of pancreatic organogenesis, which intermittently provides a basis for engineering differentiation procedures, mainly based on the use of small molecules. Small molecules are more auspicious than any other growth factors, as they have unique, valuable properties like cell-permeability, as well as a nonimmunogenic nature; furthermore, they offer immense benefits in terms of generating efficient functional beta-like cells. We also summarize advances in the generation of stem cell-derived pancreatic cell lineages, especially endocrine β-like cells or islet organoids. The successful induction of stem cells depends on the quantity and quality of available stem cells and the efficient use of small molecules.
Highlights
Diabetes mellitus (DM) is a group of metabolic diseases diagnosed by chronic hyperglycemia which is caused by insufficient insulin production or the destruction of pancreatic beta (β)-cells
As T1DM is characterized by an inadequacy of insulin due to autoimmune devastation of pancreatic β-cells [5], the current available strategy to cure the disease is exclusively dependent on the exogenous uptake of insulin
When endocrine progenitor cells (EPs) cells were treated with a cocktail of SB431542, Nicotinamide, Ascorbic acid Dibutyryl-cyclic AMP (Db-cAMP), Exendin-4, and Dorsomorphin [22], the coexpression of MAFA and insulin with a low level of NKX6.1 were seen in endocrine cells (ECs), which means that differentiated ECs were not mature
Summary
Diabetes mellitus (DM) is a group of metabolic diseases diagnosed by chronic hyperglycemia which is caused by insufficient insulin production or the destruction of pancreatic beta (β)-cells. Cellular therapy is an efficient method to cure diabetes and many other diseases related to the pancreas, which may be achieved by differentiating pancreatic β-like cells through different approaches, such as growth factors, small molecule-induced differentiation, reprogramming, and epigenetic modifications. Prodigious accomplishments have occurred in the establishment of differentiation protocols, where signaling molecules and growth factors were used in a time-dependent manner, leading to the generation of β-like cells in vitro which expressed mature β-cell markers and improved hyperglycemia in diabetic models [15,17,19,23,24]. Sci. 2020, 21, 2388 nutrients, favorable extracellular matrices [26], metabolites, and cheaper, small molecules or growth factors are required for efficient cell therapy Different strategies, such as improvements of the culture media by adding necessary factors and using bio-compatible scaffolds can be attempted to achieve long-term functional ability of pancreatic β-like cells/islet organoids after transplantation. A selection of suitable inducers is important for the cellular differentiation of β-like cells
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