skip to primary navigationskip to content
 

26.02.20 Pancreas organoids pave the way for researching diabetes, cancer and cystic fibrosis

last modified Feb 26, 2020 03:51 PM
The Huch lab and collaborators share their system for growing and maintaining pancreas organoids in culture, providing an abundant source of pancreas ductal cells that retain the characteristics of the tissue-of-origin
26.02.20 Pancreas organoids pave the way for researching diabetes, cancer and cystic fibrosis

Pancreas organoid with ductal marker (red) and pancreatic marker (green)

Long-term expansion, genomic stability and in vivo safety of adult human pancreas organoids

Georgakopoulos N et al. (2020) BMC Developmental Biology 20:4.

DOI: 10.1186/s12861-020-0209-5.

For lay explanation of the paper see the BMC Series blog:

Human Pancreas Organoids: A step closer to understanding biology & treating disease by Nicole Prior, Nikitas Georgakopoulos & Meritxell Huch

 

Abstract from original paper

Background: Pancreatic organoid systems have recently been described for the in vitro culture of pancreatic ductal cells from mouse and human. Mouse pancreatic organoids exhibit unlimited expansion potential, while previously reported human pancreas organoid (hPO) cultures do not expand efficiently long-term in a chemically defined, serum-free medium. We sought to generate a 3D culture system for long-term expansion of human pancreas ductal cells as hPOs to serve as the basis for studies of human pancreas ductal epithelium, exocrine pancreatic diseases and the development of a genomically stable replacement cell therapy for diabetes mellitus. 

Results: Our chemically defined, serum-free, human pancreas organoid culture medium supports the generation and expansion of hPOs with high efficiency from both fresh and cryopreserved primary tissue. hPOs can be expanded from a single cell, enabling their genetic manipulation and generation of clonal cultures. hPOs expanded for months in vitro maintain their ductal morphology, biomarker expression and chromosomal integrity. Xenografts of hPOs survive long-term in vivo when transplanted into the pancreas of immunodeficient mice. Notably, mouse orthotopic transplants show no signs of tumorigenicity. Crucially, our medium also supports the establishment and expansion of hPOs in a chemically defined, modifiable and scalable, biomimetic hydrogel.

Conclusions: hPOs can be expanded long-term, from both fresh and cryopreserved human pancreas tissue in a chemically defined, serum-free medium with no detectable tumorigenicity. hPOs can be clonally expanded, genetically manipulated and are amenable to culture in a chemically defined hydrogel. hPOs therefore represent an abundant source of pancreas ductal cells that retain the characteristics of the tissue-of-origin, which opens up avenues for modelling diseases of the ductal epithelium and increasing understanding of human pancreas exocrine biology as well as for producing insulin-secreting cells for the treatment of diabetes.

 

Research funded by: European Commission Horizon 2020 (H2020) Research Infrastructures. Adaptation of the culture system for human cells was funded by the LSFM4LIFE programme.

****************

Watch Meri Huch describe her previous research at the Gurdon Institute, into liver regeneration, on YouTube

Meri Huch is now Lise Meitner Max Planck Research Group leader at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden.

 

Institute reopening

The Gurdon Institute reopened on Monday 15th June. Many staff will continue to work from home, and all staff may be contacted by email.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

combinedLogo x3 trans2018

 

Share this