LUMC and Hubrecht Institute culture miniature pancreata as a new research platform

Tuesday, March 13, 2018

A team of scientists of the Hubrecht Institute and the Leiden University Medical Center (LUMC), led by Eelco de Koning, has been successful in culturing miniature organs from human pancreatic tissue. These miniature pancreata show many characteristics of developing pancreatic tissue, and are therefore suited as a new platform for studying pancreas regeneration and the development of insulin-producing cells. The article was released in Stem Cell Reports.

People with diabetes mellitus type 1 have a shortage of insulin-producing beta cells in the pancreas, leading to a defective insulin production and the cessation of glucose intake by the cells of the human body. This causes blood glucose levels to rise. To counteract this, diabetes patients have to be treated with insulin, which they have to administer themselves through injection or a small pump. Reaching stable blood glucose levels is challenging and has a large impact on the daily lives of patients.

Donor cells

Aside from administering insulin, people with diabetes type 1 can also be treated with donor beta cells through replacement therapy. However, the shortage of organ donors severely limits the number of patients eligible for transplantation of the Langerhans Islets or the entire pancreas. Another source of transplantable beta cells would therefore be welcomed as a new therapeutic option.

Miniature organs

Led by Eelco de Koning, a team of researchers from the Hubrecht Institute and the LUMC has succeeded culturing insulin-producing miniature organs in a laboratory. To accomplish this, they used a method developed by the research group of Hans Clevers, also a researcher at the Hubrecht Institute, to expand human pancreatic tissue to functional miniature pancreata. These so-called organoids bear characteristics of embryonal pancreatic tissue, meaning that these cells are able to differentiate into all cells present in the pancreas. The miniature pancreata also appeared to accomplish tasks, such as producing insulin in transplanted laboratory animals.

Platform

According to De Koning, the research of his group is the beginning of a new approach to pancreas regeneration research, including the insulin-producing cells. ‘As a platform for regeneration, we are now able to culture pancreatic tissue in a dish’, he says. ‘The cultured tissue bears the characteristics of embryonal development, and contains progenitor cells that are able to develop into insulin-producing cells. It is very nice indeed that we can observe this in the laboratory.’ De Koning thinks their research is suited for various clinical applications, such as the investigation of factors that play a role in pancreas dysfunction. De Koning: ‘In a dish, we can also research the mechanisms behind the development of insulin-producing cells. How can we stimulate this development? Which factors are involved? Using this technology platform, we might be able to map all this.’

This research was founded by the DON Foundation and the Dutch Diabetes Research Foundation. Eelco de Koning is group leader at the Hubrecht Institute (KNAW) and professor of Diabetology at the Leiden University Medical Center.

Read the article 'Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential' in Stem Cell Reports.

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