The quest to make fully functional human pancreatic beta cells from embryonic stem cells: climbing a mountain in the clouds

**From Core Set to Assemblage: On the Dynamics of Exclusion and Inclusion in the Failure to Derive Beta Cells from Embryonic Stem Cells** In this paper, we examine the controversy surrounding the Lumelsky protocol (which potentially could have transformed the procedures for differentiating embryonic stem cells into beta cells for diabetes treatment). The protocol is analyzed initially using Collins’ core set model to show how the controversy over epistemic claims was resolved (and the Lumelsky protocol deemed to be a failure). This approach is then contrasted to an analysis in terms of scientific ‘assemblages’ characterized not by the resolution of epistemic controversy, but by the ‘irresolution’ or openness of social associations amongst scientists. We suggest that scientists who jumped on the ‘Lumelsky bandwagon’ can be rehabilitated, partly because of the recognized chronic uncertainty in the stem cell fi eld. Thus, alongside the judgement, resolution and exclusion mapped by core set analysis, there is ‘understanding’, irresolution and inclusion suggested by ‘assemblage analysis’. *Key words*: core set, assemblage, stem cells

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Dual Inhibition of BMP and WNT Signals Promotes Pancreatic Differentiation from Human Pluripotent Stem Cells

Stem Cells International ◽

10.1155/2019/5026793 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 2

Author(s):

Mengtian Tan ◽

Lai Jiang ◽

Yinglei Li ◽

Wei Jiang

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Beta Cells ◽

Pluripotent Stem Cells ◽

Embryonic Stem ◽

Signal Pathways ◽

Pancreatic Differentiation ◽

Dual Inhibition ◽

Induced Pluripotent ◽

Wnt Signal

Pathological or functional loss of pancreatic beta cells is the cause of diabetes. Understanding how signaling pathways regulate pancreatic lineage and searching for combinations of signal modulators to promote pancreatic differentiation will definitely facilitate the robust generation of functional beta cells for curing hyperglycemia. In this study, we first tested the effect of several potent BMP inhibitors on pancreatic differentiation using human embryonic stem cells. Next, we examined the endodermal lineage bias upon potent BMP inhibitor treatment and further checked the crosstalk between signal pathways governing endodermal lineage determination. Furthermore, we improved current pancreatic differentiation system based on the signaling pathway study. Finally, we used human-induced pluripotent stem cells to validate our finding. We found BMP inhibitors indeed not only blocked hepatic lineage but also impeded intestinal lineage from human definitive endoderm unexpectedly. Signaling pathway analysis indicated potent BMP inhibitor resulted in the decrease of WNT signal activity and inhibition of WNT could contribute to the improved pancreatic differentiation. Herein, we combined the dual inhibition of BMP and WNT signaling and greatly enhanced human pancreatic progenitor differentiation as well as beta cell generation from both embryonic stem cells and induced pluripotent stem cells. Conclusively, our present work identified the crosstalk between the BMP and WNT signal pathways during human endoderm patterning and pancreas specification, and provided an improved in vitro pancreatic directed differentiation protocol from human pluripotent stem cells.

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