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Highlights in Chemical Biology

Chemical biology news from across RSC Publishing.

A different approach to stem cell research

02 December 2008

Two recent papers published in RSC journal Integrative Biology highlight new details about adult stem cells. 

John Connelly of the Wellcome Trust Centre for Stem Cell Research at the University of Cambridge, UK, describes the technological approaches used by the research teams as representing 'an exciting new direction in the field of stem cell biology.'

"Understanding how stem cells convert into different cell types is important for the field of stem cell therapeutics to develop"
We all have stem cells which, localised in niches throughout the body, provide cells throughout our lifetimes. However, whilst stem cells have been used to replace and repair damaged tissue, very little is known about how the cells can do this. Understanding how stem cells convert into different cell types is important for the field of stem cell therapeutics to develop.

A group at the Lawrence Berkeley National Laboratory, US, led by Mark LaBarge and Mina Bissell, has teamed up with a group at the Panum Institute in Copenhagen, Denmark, to investigate human mammary stem cells, which can become any type of breast tissue. Meanwhile, Matthias Lutolf and a team at Stanford University School of Medicine, US, have investigated hematopoietic (blood forming) stem cells (HSCs) in adult mice.

Microarrays of stem cells

Microarray technology was used to study stem cells held in many different environments

The two teams used microarray technologies to study the stem cells. The aim for both groups was to establish how and why these cells specialise into different cell types and using arrays allowed them to conduct many experiments simultaneously. Working on the hypothesis that a stem cell's behaviour is instructed by its surroundings, the groups created model environments to mimic the complex microenvironment that stem cells inhabit within the adult body. This allowed them to investigate how the environment influences stem cells to change and could lead to ways of influencing stem cell function outside of the body.

Bissell and LaBarge's group used their microarrays to expose stem cells to many different proteins and biological molecules in 8000 different combinations. The group was able to identify which conditions led the cells to convert into different breast cell types, including luminal epithelial cells, cells that can become cancerous. They were also able to suggest which components would keep the cells in their original, unspecialised state. Bissell says that she hopes that this type of approach 'will teach us how to direct stem cell function in a therapeutic setting and possibly to reprogram non-stem cells to acquire other stem cell fates.'

"Cultures of HSCs that could maintain their characteristic properties of self renewal could provide an unlimited source of cells for therapeutic transplantation"
- Matthias Lutolf
Lutolf's group, by contrast, exposed the stem cells to a more limited set of molecules but used microwell arrays to allow them to view individual cells as they specialised. They were able to identify key regulators in maintaining the HSCs as stem cells. Lutolf says that these findings could be very valuable for scientists struggling to grow HSCs in the lab. 'These cells do not replicate without rapidly differentiating in vitro,' he adds. He explains that culturing stem cells in vitro would be 'a very important achievement because cultures of HSCs that could maintain their characteristic properties of self renewal could provide an unlimited source of cells for therapeutic transplantation.' 

Both groups are now working to expand their efforts, to investigate the effects on stem cells of the microenvironments in the body and work towards using adult stem cells in a therapeutic setting.

Laura Howes

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Link to journal article

Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments
Mark A. LaBarge, Celeste M. Nelson, Rene Villadsen, Agla Fridriksdottir, Jason R. Ruth, Martha R. Stampfer, Ole W. Petersen and Mina J. Bissell, Integr. Biol., 2009, 1, 70
DOI: 10.1039/b816472j

Perturbation of single hematopoietic stem cell fates in artificial niches
Matthias P. Lutolf, Regis Doyonnas, Karen Havenstrite, Kassie Koleckar and Helen M. Blau, Integr. Biol., 2009, 1, 59
DOI: 10.1039/b815718a

Also of interest

Mina Bissell

Interview: Integrative biology

26 November 2008

Mina Bissell talks to Kathleen Too about the concept and future of integrative biology

Snapshots of specialising cells

Researchers in Germany have used infrared spectroscopy to spot stem cells as they change into new cell types.

Exploring stem cell biology with small molecules
Shuibing Chen, Simon Hilcove and Sheng Ding, Mol. BioSyst., 2006, 2, 18
DOI: 10.1039/b512000b