Differentiation of human fetal liver stem cells and pancreas derived progenitor cells to pancreatic beta-cells

Lead Research Organisation: University of Edinburgh
Department Name: Biomedical Sciences


In recent years there has been significant advances in the treatment of diabetes by the transplantation of replacement beta-cells (the type of cell destroyed in the course of the disease). At present however, the ability to perform cell transplantation is limited by the availability of suitable donor cells in significant numbers. This project aims to isolate a population of cells from the developing liver and pancreas that can be expanded in culture and may eventually be used to provide replacement cells in order to treat this condition.
During fetal development, the pancreas (containing beta-cells) and the liver share a common developmental origin, suggesting that they may share some common stem/progenitor cells. Our project aims to isolate a potential type of progenitor cell based on the presence of a cell surface marker protein (Thy-1+). We then aim to compare cells from both fetal liver and pancreas for their capacity to change into beta-cells under specific culture conditions and to test and compare these cells grown in the laboratory to those found normally in the body.

Technical Summary

The aim of this project is to develop an optimised protocol to isolate and expand a Thy-1+ putative progenitor cell population from human fetal liver and pancreas and subsequently characterise the beta-cell differentiation potential of these cells.
1. Isolation of human mid-trimester fetal Thy-1+ human fetal liver stem cells (hFLSCs) and Thy-1+ human pancreas derived progenitor cells (PDPCs) by immuno-sorting, with subsequent characterisation.
2. Cross comparison of both liver and pancreas derived Thy-1+ cell populations via characterisation of marker analysis by RT-PCR (CD90, CD44, CD49f, CD147, c-KIT, CD71, CD45, CD31, CD34) and Affymetrix microarray studies.
3. Cross comparison of Thy-1+ cell populations via in vitro differentiation to hepatic and pancreatic lineages to demonstrate bi-potentiality of Thy-1+ cells to both tissue types. This includes the induction of beta-cell differentiation of both cell populations using optimised culture conditions.
4. To induce differentiation to beta-cell lineage with induced plasmid delivered protein expression of PDX-1, Pax4 and ngn3, with further cross comparison of Thy-1+ differentiated beta
Title Fetal derived Pancreatic MSCs 
Description During this project we are in the process of developing a mesenchymal stem cell line derived from fetal pancreas tissue. 
Type Of Material Cell line 
Provided To Others? No  
Impact This cell line will in part form the basis for use in upcoming animal transplantation models for diabetes 
Description Collaboration with Aberdeen 
Organisation University of Aberdeen
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Analysis of a similar adult derived stem cell population to our own fetal pancreas derived population. As we have developed experience analyzing our own cell population by flow cytometry, IHC and mesenchymal differentiation similar protocols have been conducted with those cells provided by our collaborators in order to further characterise and define their cell populations.
Collaborator Contribution Our partners in this collaboration have further analysed and compared the differentiation capacity of our fetal derived cells in comparison to their adult derived cells in the context of the pancreatic lineage.
Impact First set of data and outcomes has currently been re-submitted for publication following amendments from the initial submission.
Start Year 2010
Description Collaboration with Glasgow 
Organisation University of Glasgow
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Provision of fetally derived cells of a similar nature to those previously investigated by our collaborators in order to contrast and compare the senescent profile of these differing populations.
Collaborator Contribution Access, experience and guidance with regards to the analysis of our cell population with respect to its senescent profile throughout the lifetime of these cells. Use of an established platform to assess response to oxidative stimuli.
Impact First publication current in final preparation prior to submission.
Start Year 2011