Reprogramming of Human Pancreatic Organoid Cells into Insulin-Producing beta-Like Cells by Small Molecules and in Vitro Transcribed Modified mRNA Encoding Neurogenin 3 Transcription Factor

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F19%3A00078698" target="_blank" >RIV/00023001:_____/19:00078698 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/19:10401685

Result on the web

<a href="https://fb.cuni.cz/file/5896/fb2019a0011.pdf" target="_blank" >https://fb.cuni.cz/file/5896/fb2019a0011.pdf</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Reprogramming of Human Pancreatic Organoid Cells into Insulin-Producing beta-Like Cells by Small Molecules and in Vitro Transcribed Modified mRNA Encoding Neurogenin 3 Transcription Factor

Original language 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 beta-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 beta-cells.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/NV15-25924A" target="_blank" >NV15-25924A: Transplantation therapy of diabetes with insulin-producing cells derived by reprogramming of non-endocrine pancreatic cells</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Folia biologica (Praha)

ISSN

0015-5500

e-ISSN

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Volume of the periodical

65

Issue of the periodical within the volume

3

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

15

Pages from-to

109-123

UT code for WoS article

000500271800001

EID of the result in the Scopus database

2-s2.0-85073656963