Reprogramming of human pancreatic organoid cells into insulin-producing β-like cells by small molecules and in vitro transcribed modified mRNA encoding neurogenin 3 transcription factor

Title:

Reprogramming of human pancreatic organoid cells into insulin-producing β-like cells by small molecules and in vitro transcribed modified mRNA encoding neurogenin 3 transcription factor

Creator:

Koblas, T., Leontovyc, I., Loukotova, S., and Saudek, F.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:4e9404a5-7932-4642-8afa-f7e9650c99f8
uuid:4e9404a5-7932-4642-8afa-f7e9650c99f8

Subject:

diabetes, organoid, reprogramming, synthetic mRNA, in vitro transcription, IVT, neurogenin 3, β-cell, insulin, TGF, RepSox, and small molecules

Type:

model:article and TEXT

Format:

bez média and svazek

Description:

Reprogramming of non-endocrine pancreatic cells into insulin-producing cells represents a promising therapeutic approach for the restoration of endogenous insulin production in diabetic patients. In this paper, we report that human organoid cells derived from the pancreatic tissue can be reprogrammed into the insulin-producing cells (IPCs) by the combination of in vitro transcribed modified mRNA encoding transcription factor neurogenin 3 and small molecules modulating the epigenetic state and signalling pathways. Upon the reprogramming, IPCs formed 4.6 ± 1.2 % of the total cells and expressed typical markers (insulin, glucokinase, ABCC8, KCNJ11, SLC2A2, SLC30A8) and transcription factors (PDX1, NEUROD1, MAFA, NKX2.2, NKX6.1, PAX4, PAX6) needed for the proper function of pancreatic β-cells. Additionally, we have revealed a positive effect of ALK5 inhibitor RepSox on the overall reprogramming efficiency. However, the reprogrammed IPCs possessed only a partial insulin-secretory capacity, as they were not able to respond to the changes in the extracellular glucose concentration by increasing insulin secretion. Based on the achieved results we conclude that due to the incomplete reprogramming, the IPCs have immature character and only partial properties of native human β-cells. and Corresponding author: Tomas Koblas

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Coverage:

[109]-123

Source:

Folia biologica | 2019 Volume:65 | Number:3

Harvested from:

CDK

Metadata only:

false