Stem cells differentiation into insulin-producing cells (IPCs): recent advances and current challenges

Abstract

Type 1 diabetes mellitus (T1D) is a chronic disease characterized by an autoimmune destruction of insulin-producing β-pancreatic cells. Although many advances have been achieved in T1D treatment, current therapy strategies are often unable to maintain perfect control of glycemic levels. Several studies are searching for new and improved methodologies for expansion of β-cell cultures in vitro to increase the supply of these cells for pancreatic islets replacement therapy. A promising approach consists of differentiation of stem cells into insulin-producing cells (IPCs) in sufficient number and functional status to be transplanted. Differentiation protocols have been designed using consecutive cytokines or signaling modulator treatments, at specific dosages, to activate or inhibit the main signaling pathways that control the differentiation of induced pluripotent stem cells (iPSCs) into pancreatic β-cells. Here, we provide an overview of the current approaches and achievements in obtaining stem cell-derived β-cells and the numerous challenges, which still need to be overcome to achieve this goal. Clinical translation of stem cells-derived β-cells for efficient maintenance of long-term euglycemia remains a major issue. Therefore, research efforts have been directed to the final steps of in vitro differentiation, aiming at production of functional and mature β-cells and integration of interdisciplinary fields to generate efficient cell therapy strategies capable of reversing the clinical outcome of T1D.

Using single‐cell multi‐omics screening of human fetal pancreas to identify novel players in human beta cell development

“…Close spatial proximity of the Schwann cells to the endocrine progenitors suggests that paracrine signalling will be important in influencing differentiation, and further work is required to identify which, if any, of the ligand‐receptor pairs are critical for islet cell development. The lack of an in vitro niche containing the appropriate signalling factors required for full beta cell specification is thought to contribute to the immature cells produced by current stem cell differentiation protocols, 59 , 60 leading to the requirement for an additional in vivo maturation stage. A thorough understanding of the pancreas microenvironment in which the endocrine progenitors mature may, therefore, reveal signalling factors or ligands that can be included in current differentiation cocktails to increase the maturation of stem cell‐derived beta cells in vitro.…”

Correction: Stem cells differentiation into insulin-producing cells (IPCs): recent advances and current challenges

“…On page 8 of the original article [ 1 ], in the sentence: "… differentiation of iPSCs in pancreatic β-cells, namely Wnt; Nodal/Activin A; BMPs; FGF; EGF (epidermal growth factor); Hedgehog; retinoid; and Notch (Fig. 1).".…”

Pancreatic islets implanted in an irreversible electroporation generated extracellular matrix in the liver

“…7 As the technology to develop stem cell-derived beta-cells and islets mature, demand for islet transplantation is expected to increase and the procedure become more widespread. 8 Identification of new and improved methods for pancreatic islets implantation has become an important area of research. 9,10 In an attempt to overcome deficiencies related to the injection of pancreatic islets through the portal vein, while retaining the advantages of islet implantation into the liver, Fujita et al reported on a method of direct transplant of pancreatic islets, in the form of an isletcell-sheet, onto the liver surface.…”