Differentiation of Human Pluripotent Stem Cells into Pancreatic Beta-cell Precursors in a 2D Culture System

10.3791/63298 ◽  
2021 ◽  
Author(s):  
Bushra Memon ◽  
Essam M. Abdelalim
Keyword(s):  
Stem Cells ◽  
Beta Cell ◽  
Pluripotent Stem Cells ◽  
Culture System ◽  
Pancreatic Beta Cell ◽  
Human Pluripotent Stem Cells

Chemically defined and growth-factor-free culture system for the expansion and derivation of human pluripotent stem cells

2018 ◽  
Vol 2 (3) ◽  
pp. 173-182 ◽  
Author(s):  
Shin-ya Yasuda ◽  
Tatsuhiko Ikeda ◽  
Hosein Shahsavarani ◽  
Noriko Yoshida ◽  
Bhavana Nayer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Pluripotent Stem Cells ◽  
Culture System ◽  
Human Pluripotent Stem Cells

Scaling up a chemically-defined aggregate-based suspension culture system for neural commitment of human pluripotent stem cells

2016 ◽  
Vol 11 (12) ◽  
pp. 1628-1638 ◽  
Author(s):  
Cláudia C. Miranda ◽  
Tiago G. Fernandes ◽  
M. Margarida Diogo ◽  
Joaquim M.S. Cabral
Keyword(s):  
Stem Cells ◽  
Suspension Culture ◽  
Pluripotent Stem Cells ◽  
Culture System ◽  
Scaling Up ◽  
Human Pluripotent Stem Cells

New insights into human beta cell biology using human pluripotent stem cells

2020 ◽  
Vol 103 ◽  
pp. 31-40 ◽  
Author(s):  
Nur Shabrina Amirruddin ◽  
Blaise Su Jun Low ◽  
Kok Onn Lee ◽  
E Shyong Tai ◽  
Adrian Kee Keong Teo
Keyword(s):  
Stem Cells ◽  
Beta Cell ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Human Pluripotent Stem Cells ◽  
Human Beta Cell

scholarly journals miR-212/132-Enriched Extracellular Vesicles Promote Differentiation of Induced Pluripotent Stem Cells Into Pancreatic Beta Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Chunyu Bai ◽  
Qiwei Ren ◽  
Haifeng Liu ◽  
Xiangchen Li ◽  
Weijun Guan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Beta Cell ◽  
Induced Pluripotent Stem Cells ◽  
Beta Cells ◽  
Extracellular Vesicles ◽  
Pluripotent Stem Cells ◽  
Pancreatic Beta Cells ◽  
Pancreatic Beta Cell ◽  
Induced Pluripotent

Pancreatic beta cell transplantation is the ideal method for treatment of type 1 diabetes mellitus (T1DM), and the generation of beta cells from induced pluripotent stem cells (iPSCs) of patients is a promising strategy. In this study, we improved a previous strategy to produce beta cells using extracellular vesicles (EVs) derived from mature beta cells and differentiated beta cells from iPSCs (i-Beta cells), which secreted insulin under glucose stimulation in vitro and ameliorated hyperglycemia in vivo. Mechanistic analyses revealed that EV-carried microRNA (miR)-212/132 (EV-miR-212/132) directly bound to the 3′ UTR of FBW7 to prevent its translation and FBW7 combined with NGN3 to accelerate its proteasomal degradation. EV-miR-212/132 stabilized NGN3 expression to promote differentiation of endocrine cells from induced iPSCs. Moreover, NGN3 bound to PDX1 to enhance transcription of endogenous miR-212/132 and formed a positive regulatory circuit that maintained the functions of mature pancreatic beta cells.ConclusionThis study describes a novel approach for beta cell production and supports the use of iPSCs for cell replacement therapy of T1DM.

scholarly journals Nicotinamide promotes differentiation of pancreatic endocrine progenitors from human pluripotent stem cells through poly (ADP-ribose) polymerase inhibition

2020 ◽  
Author(s):  
Curtis Woodford ◽  
Ting Yin ◽  
Huntley H Chang ◽  
Romario Regeenes ◽  
Ravi N Vellanki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Oxygen Consumption ◽  
Beta Cell ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Salvage Pathway ◽  
Vitamin B3 ◽  
Nadh Ratio ◽  
Mouse Islets ◽  
Endocrine Progenitors

AbstractThe generation of pancreatic endocrine progenitor cells is an important step in the differentiation of beta cells from human pluripotent stem cells (hPSC). This stage is marked by the expression of Nkx6.1, a transcription factor with well understood downstream targets but with unclear upstream regulators. In hPSC differentiation, Nkx6.1 is strongly induced by nicotinamide, a derivative of vitamin B3, which has three known functions within a cell. Nicotinamide inhibits two classes of enzymes known as poly-ADP-ribose polymerases (PARPs) and sirtuins. It also contributes to the cellular pool of nicotinamide adenosine deoxynucleotide (NAD+) after conversion in the nicotinamide salvage pathway. Induction of Nkx6.1 expression in pancreatic endocrine progenitors by nicotinamide was mimicked by 3 PARP inhibitors (PJ34, olaparib, NU1025). Small molecule inhibition of the nicotinamide salvage pathway reduced Nkx6.1 expression but not Pdx1 expression and caused alteration in NAD+/NADH ratio. Nkx6.1 expression was not affected by sirtuin inhibition. Metabolic profiling of differentiating pancreatic and endocrine progenitors showed that oxygen consumption increases as differentiation progresses, and that nicotinamide reduces oxygen consumption rate. Expression of Nkx6.1 and other beta cell related genes, including Ins2 and Pdx1 increased in mouse islets after exposure to nicotinamide. In summary, nicotinamide induced Nkx6.1 expression in differentiating human pancreatic endocrine progenitors through inhibition of the PARP family of enzymes. Nicotinamide administration was also associated with increased NAD+/NADH ratio, without affecting Nkx6.1 expression. Similarly, the association between nicotinamide and Nkx6.1 expression was also seen in isolated mouse islets. These observations show a link between the regulation of beta cell identity and the effectors of NAD+ metabolism, suggesting possible therapeutic targets in the field of diabetes.

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