Reprogramming of liver cells into insulin-producing cells

Meivar‐Levy, Irit; Ferber, Sarah

doi:10.1016/j.beem.2015.10.006

Cited by 21 publications

(11 citation statements)

References 73 publications

(97 reference statements)

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“…3). Several studies have demonstrated that adult or fetal liver cells and biliary epithelial cells are capable of reprogramming into IPCs by inducing the expression of endocrine pancreaticspecific transcription factors [95][96][97][98]. The in vivo data showed that these hepatic cell-derived IPCs could ameliorate hyperglycemia upon implantation into diabetic mice.…”

Section: Differentiation Of Liver Cellsmentioning

confidence: 99%

Current progress in stem cell therapy for type 1 diabetes mellitus

2020

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Type 1 diabetes mellitus (T1DM) is the most common chronic autoimmune disease in young patients and is characterized by the loss of pancreatic β cells; as a result, the body becomes insulin deficient and hyperglycemic. Administration or injection of exogenous insulin cannot mimic the endogenous insulin secreted by a healthy pancreas. Pancreas and islet transplantation have emerged as promising treatments for reconstructing the normal regulation of blood glucose in T1DM patients. However, a critical shortage of pancreases and islets derived from human organ donors, complications associated with transplantations, high cost, and limited procedural availability remain bottlenecks in the widespread application of these strategies. Attempts have been directed to accommodate the increasing population of patients with T1DM. Stem cell therapy holds great potential for curing patients with T1DM. With the advent of research on stem cell therapy for various diseases, breakthroughs in stem cell-based therapy for T1DM have been reported. However, many unsolved issues need to be addressed before stem cell therapy will be clinically feasible for diabetic patients. In this review, we discuss the current research advances in strategies to obtain insulin-producing cells (IPCs) from different precursor cells and in stem cell-based therapies for diabetes.

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Section: Differentiation Of Liver Cellsmentioning

confidence: 99%

Current progress in stem cell therapy for type 1 diabetes mellitus

2020

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“…Several transdifferentiated insulin-producing cells from various cell sources have been reported [ 22 ]. Liver cells, in particular, are thought to be promising candidates because the proliferative capacity of the liver depends on tissue-specific progenitors [ 23 ]. In general, however, these progenitors are thought to emerge in damaged liver after the administration of a hepatotoxin [ 24 , 25 ], and specific genetic modifications are required to isolate these cells from normal liver [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Treatment with specific soluble factors promotes the functional maturation of transcription factor-mediated, pancreatic transdifferentiated cells

et al. 2018

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Pancreatic lineage-specific transcription factors (TFs) display instructive roles in converting adult cells to endocrine pancreatic cells through a process known as transdifferentiation. However, little is known about potential factors capable of accelerating transdifferentiation following transduction to achieve the functional maturation of transdifferentiated cells. In this study, we demonstrated, using adult liver-derived progenitor cells, that soluble factors utilized in pancreatic differentiation protocols of pluripotent stem cells promote functional maturation of TFs-mediated transdifferentiated cells. Treatment with an N2 supplement in combination with three soluble factors (glucagon-like peptide-1 [GLP-1] receptor agonist, notch inhibitor, and transforming growth factor-β [TGF-β] inhibitor) enhanced liver-to-pancreas transdifferentiation based on the following findings: i) the incidence of c-peptide-positive cells increased by approximately 1.2-fold after the aforementioned treatment; ii) the c-peptide expression level in the treated cells increased by approximately 12-fold as compared with the level in the untreated cells; iii) the treated cells secreted insulin in a glucose-dependent manner, whereas the untreated cells did not; and iv) transplantation of treated-transdifferentiated cells into streptozotocin-induced immunodeficient diabetic mice led to the amelioration of hyperglycemia. These results suggest that treatment with specific soluble factors promotes the functional maturation of transdifferentiated cells. Our findings could facilitate the development of new modalities for cell-replacement therapy for patients with diabetes.

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“…In addition, liver shares with pancreas the glucose responsiveness. Thus, hepatic cells represent a good therapeutic potential candidate for β cell generation ( 67 , 68 ). Ferber and colleagues were the first researchers demonstrating that in vivo adenoviral-mediated ectopic expression of PDX1 in liver generated increase of silent endogenous INS gene expression.…”

Section: Liver-to-βmentioning

confidence: 99%

The potential and challenges of alternative sources of β cells for the cure of type 1 diabetes

Cito

Pellegrini

Piemonti

et al. 2018

Endocrine Connections

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The experience in the field of islet transplantation shows that it is possible to replace β cells in a patient with type 1 diabetes (T1D), but this cell therapy is limited by the scarcity of organ donors and by the danger associated to the immunosuppressive drugs. Stem cell therapy is becoming a concrete opportunity to treat various diseases. In particular, for a disease like T1D, caused by the loss of a single specific cell type that does not need to be transplanted back in its originating site to perform its function, a stem cell-based cell replacement therapy seems to be the ideal cure. New and infinite sources of β cells are strongly required. In this review, we make an overview of the most promising and advanced β cell production strategies. Particular hope is placed in pluripotent stem cells (PSC), both embryonic (ESC) and induced pluripotent stem cells (iPSC). The first phase 1/2 clinical trials with ESC-derived pancreatic progenitor cells are ongoing in the United States and Canada, but a successful strategy for the use of PSC in patients with diabetes has still to overcome several important hurdles. Another promising strategy of generation of new β cells is the transdifferentiation of adult cells, both intra-pancreatic, such as alpha, exocrine and ductal cells or extra-pancreatic, in particular liver cells. Finally, new advances in gene editing technologies have given impetus to research on the production of human organs in chimeric animals and on in situ reprogramming of adult cells through in vivo target gene activation.

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Reprogramming of liver cells into insulin-producing cells

Cited by 21 publications

References 73 publications

Current progress in stem cell therapy for type 1 diabetes mellitus

Current progress in stem cell therapy for type 1 diabetes mellitus

Treatment with specific soluble factors promotes the functional maturation of transcription factor-mediated, pancreatic transdifferentiated cells

The potential and challenges of alternative sources of β cells for the cure of type 1 diabetes

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