Large scale, cost-effective stem cell factories able to keep up with demand for new therapies to treat a range of human illnesses are a step closer to reality, thanks to a scientific breakthrough involving researchers at The University of Nottingham.
In a paper published in the September edition of the prestigious journal Nature Materials, a team of Nottingham scientists led by Professor Morgan Alexander in the University’s School of Pharmacy, reveal they have discovered some man-made acrylate polymers which allow stem cells to reproduce while maintaining their pluripotency.
Professor Alexander said: “This is an important breakthrough which could have significant implications for a wide range of stem cell therapies, including cancer, heart failure, muscle damage and a number of neurological disorders such as Parkinson’s and Huntington’s.
One of these new manmade materials may translate into an automated method of growing pluripotent stem cells which will be able to keep up with demand from emerging therapies that will require cells on an industrial scale, while being both cost-effective and safer for patients.”
The research, a collaboration with colleagues Bob Langer, Dan Anderson, Rudolf Jaenisch and Krystyn Van Vliet at the Massachusetts Institute of Technology (MIT), involved using polymer microarrays — standard scientific glass slides with 1,700 polymer spots on the surface. Stem cells tagged with a fluorescent agent which allow them to be seen were placed onto the polymer spots. The scientists were then able to watch the stem cells and observe which polymers were most successful at promoting the most growth while also maintaining the pluripotency of the stem cells. Critically, in this paper the influence of the material properties was investigated though analysis of the polymer micro array spots.
Both human embryonic stem cells and induced pluripotent stem cells can self-renew indefinitely in culture; however, present methods to clonally grow them are inefficient and poorly defined for genetic manipulation and therapeutic purposes. Here we develop the first chemically defined, xeno-free, feeder-free synthetic substrates to support robust self-renewal of fully dissociated human embryonic stem and induced pluripotent stem cells. Material properties including wettability, surface topography, surface chemistry and indentation elastic modulus of all polymeric substrates were quantified using high-throughput methods to develop structure–function relationships between material properties and biological performance. These analyses show that optimal human embryonic stem cell substrates are generated from monomers with high acrylate content, have a moderate wettability and employ integrin αvβ3 and αvβ5 engagement with adsorbed vitronectin to promote colony formation. The structure–function methodology employed herein provides a general framework for the combinatorial development of synthetic substrates for stem cell culture.
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