Webinar Details

Efficient generation of pancreatic beta cell precursors from human pluripotent stem cells

21st September, 2018-05:00 PM
845
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ID
A00554CA1800234

العربية

Pancreatic B cell replacement therapy is considered as a potential strategy to treat T1D and advanced cases of T2D. To date, transplantation of pancreatic islets from cadavers is the most effective approach for treating diabetic patients, but this approach has limitations in terms of the necessity of strong immunosuppressive drugs and the shortage of matching donors. Alternatively, human pluripotent stem cells (hPSCs), including human embryonic SCs (hESCs) and hiPSCs, can be differentiated into insulin-secreting beta cells that have a great potential for treating diabetes. However, generation of functional insulin-secreting cells similar to those found naturally in the pancreas is, so far, a work in progress. Indeed, few studies showed that they generated functional beta cells from hPSCs, but those cells were low in efficiency and functionality, creating a major obstacle to the use of these cells for cellular therapy. Recent progress showed that patients with diabetes could be transplanted with hPSC-derived pancreatic progenitors co-expressing the two transcription factors (TFs), PDX1 and NKX6.1. After transplantation, those progenitors are converted into functional insulin-secreting beta cells inside the patient’s body. Recently, we have established an efficient protocol for maximizing generation of PDX1+/NKX6.1+ PPs from hPSCs. We enhanced the generation of PDX1+/NKX6.1+ population, by manipulating in vitro culture conditions. Our optimized protocol dramatically increased the expression of NKX6.1, leading to an increase in the proportion of PDX1+/NKX6.1+ progenitors (~90%), higher than the previously published protocols, as well as upregulated key TFs controlling pancreatic development. The improved efficiency of pancreatic differentiation was complemented by an inhibited hepatic specification and an increased proliferation of NKX6.1+ cells. Further differentiation validated the ability of our PDX1+/NKX6.1+ progenitors to generate NGN3+ endocrine progenitors. Interestingly, we were able to enrich a novel PDX1-/NKX6.1+ population by manipulating re-plating density, that oriented themselves in three-dimensional clusters.
Our findings provide a novel technique that facilitates appropriate cellular rearrangement in monolayer culture to yield a high proportion of PDX1+/NKX6.1+ PPs with an elevated self-replicating capacity, thereby aiding scalable production of functional ? cells from hPSCs in vitro. Our innovative method also supports the existence of two independent NKX6.1+ pancreatic progenitors during human pancreatic development and the novel PDX1-/NKX6.1+ population may be involved in a unique trajectory to generate ? cells in humans.
In this webinar, I will present our recently published work on generating distinct pancreatic progenitor populations from hPSCs.

Stem Cells & Cancer Stem Cells

English

21st September, 2018

5:00 PM (UAE Time)

30 mins

Yes, Issued by ( MEMBS )

Free

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