ES cells showing promise in tissue therapy

By Susan Williamson
Thursday, 07 April, 2005

A new technique that involves seeding 3D biodegradable polymer scaffolds with human embryonic stem (hES) cells is showing promise as a way to create human tissues for therapeutic applications, an Israeli researcher has told a workshop in Sydney.

Dr Shulamit Levenberg, of the Israeli technology institute Technion, was the plenary speaker at the Sydney stem cell workshop.

The research was done in Robert Langer's lab at MIT, where Levenberg was a postdoc and research associate. She has been with the faculty of biomedical engineering at the Technion for about five months now, and is continuing the work which focuses on the use of biodegradable 3D polymer scaffolds to induce differentiation of hES cells into tissues.

The hES cells, which have the potential to differentiate into numerous different cell types, were seeded onto the scaffold in an undifferentiated state. The seeded scaffold structure was then treated with growth factors, such as retinoic acid, transforming growth factor beta, activin-A and insulin-like growth factor, which are known to stimulate the formation of specific cell types.

"We put a mixture of stem cells on the scaffold before they had differentiated and, given the right growth factors, we could induce tissue formation in a specific direction," explained Levenberg.

Surprisingly, the hES cells not only proliferated and differentiated, they organised themselves into 3D structures with characteristics of developing neural tissues, cartilage, liver, and blood vessel-like networks.

"For example, the stem cells were able to differentiate into endothelial cells by themselves and, with the support of the 3D scaffold structure, they were able to develop into a network of capillaries by themselves," said Levenberg. "Whole networks of blood vessels formed in the scaffolds."

The scaffold is made up of two different polymers that degrade at different rates, thus giving the cells room to grow and organise themselves whilst still providing some support.

"The cells organise into tubes and we give them enough room to organise themselves," said Levenberg. "All the pores are interconnected so the cells are able to talk to each other and migrate around the structure."

Levenberg said the researchers could change the size of the scaffold, the size of the pores, and make scaffolds that contain mixtures of large and small pores. The work is ongoing and the researchers are pursuing a better understanding of the role of the polymer scaffold in the process, such as its mechanical properties, the effects of the mechanical forces of the cells, pore size and other structural features such as physical cues that guide cells in their movement and orientation.

Other speakers at the workshop, which addressed tissue therapies and commercialisation, included Mesoblast chief scientist Silviu Itescu, Megan Munsie of Stem Cell Sciences, Steven Mercer of Tissue Therapies, Justin Cooper White of UQ, Pauline Doran of UNSW, and Kerry Doyle of the NSW government's ministry for science and medical research.

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