New stem cell method produces millions of human brain and muscle cells in days
Wellcome Trust Sanger Institute scientists and their collaborators at the University of Cambridge have created a new technique that simplifies the production of human brain and muscle cells – allowing millions of functional cells to be generated in just a few days. The results published today (23 March) in Stem Cell Reports open the door to producing a diversity of new cell types that could not be made before in order to study disease.
Human pluripotent stem cells offer the ability to create any tissue, including those which are typically hard to access, such as brain cells. They hold huge potential for studying human development and the impact of diseases, including cancer, Alzheimer’s, Multiple Sclerosis, and heart disease.
In a human, it takes 9-12 months for a single brain cell to develop fully. To create human brain cells, including grey matter (neurons) and white matter (oligodendrocytes) from an induced pluripotent stem cell, it can take between three and twenty weeks using current methods. However, these methods are complex and time-consuming, often producing a mixed population of cells.
The new platform technology, OPTi-OX, optimises the way of switching on genes in human stem cells. Scientists applied OPTi-OX to the production of millions of nearly identical cells in a matter of days. In addition to the neurons, oligodendrocytes, and muscle cells the scientists created in the study, OPTi-OX holds the possibility of generating any cell type at unprecedented purities, in this short timeframe.
To produce the neurons, oligodendrocytes, and muscle cells, scientists altered the DNA in the stem cells. By switching on carefully selected genes, the team “reprogrammed” the stem cells and created a large and nearly pure population of identical cells. The ability to produce as many cells as desired combined with the speed of the development gives an advantage over other methods. The new method opens the door to drug discovery, and potentially therapeutic applications in which large amounts of cells are needed.
“What is really exciting is we only needed to change a few ingredients – transcription factors – to produce the exact cells we wanted in less than a week. We over-expressed factors that make stem cells directly convert into the desired cells, thereby bypassing development and shortening the process to just a few days.”
Dr Ludovic Vallier An author of the study, from the Wellcome Trust Sanger Institute and Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute
OPTi-OX has applications in various projects, including the possibility to generate new cell types which may be uncovered by the Human Cell Atlas. The ability to produce human cells so quickly means the new method will facilitate more research.
“When we receive a wealth of new information on the discovery of new cells from large scale projects, like the Human Cell Atlas, it means we’ll be able to apply this method to produce any cell type in the body, but in a dish.”
Daniel Ortmann Joint first author of the study, from the University of Cambridge
“Neurons produced in this study are already being used to understand brain development and function. This method opens the doors to producing all sorts of hard-to-access cells and tissues so we can better our understanding of diseases and the response of these tissues to newly developed therapeutics.”
Mark Kotter Lead author and Clinician from the University of Cambridge
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Additional Quote:
“Creating specific types of cells from pluripotent stem cells holds enormous promise in studying human diseases in a petri dish, screening for potential drugs, and as a treatment to mend damaged organs.
“However, creating such cells quickly in the laboratory is a challenge. Here, researchers have made an important advance by finding a new way to generate large numbers of such cells quickly. The authors have specifically generated neuronal cells and muscle cells but I am certain the approach can be applied to heart cells also.
“The British Heart Foundation is committed to funding research to harness the potential of stem cells for heart disease patients and currently funds three centres of regenerative medicine which are helping us take significant steps towards our ultimate goal of finding a cure for heart failure.”
Professor Sir Nilesh Samani Medical Director at the British Heart Foundation
OPTi-OX
The method is called OPTi-OX, which stands for OPTimised inducible OvereXpression. It refers to the controllable expression of inducible transgenes in human pluripotent stem cells and their derivatives. Elpis BioMed Ltd. is a spin out company that has been set up to make the technology commercially available.
Funding:
This work was supported by Wellcome, the Medical Research Council, the German Research Foundation, the British Heart Foundation, The National Institute for Health Research UK and the Qatar Foundation.
Publications:
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University of Cambridge
The mission of the University of Cambridge is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. To date, 96 affiliates of the University have won the Nobel Prize. Founded in 1209, the University comprises 31 autonomous Colleges, which admit undergraduates and provide small-group tuition, and 150 departments, faculties and institutions. Cambridge is a global university. Its 19,000 student body includes 3,700 international students from 120 countries. Cambridge researchers collaborate with colleagues worldwide, and the University has established larger-scale partnerships in Asia, Africa and America. The University sits at the heart of one of the world’s largest technology clusters. The ‘Cambridge Phenomenon’ has created 1,500 hi-tech companies, 14 of them valued at over US$1 billion and two at over US$10 billion. Cambridge promotes the interface between academia and business, and has a global reputation for innovation.
The Wellcome Trust Sanger Institute
The Wellcome Trust Sanger Institute is one of the world’s leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.
Wellcome
Wellcome exists to improve health for everyone by helping great ideas to thrive. We’re a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate.
The Wellcome Trust-Medical Research Council Stem Cell Institute
The Wellcome Trust-Medical Research Council Stem Cell Institute explores and defines the properties of stem cells to establish their true medical potential. Leading research scientists, technology specialists and doctors work side by side to create a world-leading centre of excellence in stem cell biology and medicine. The Institute also provides high level training for young researchers from around the world and collaborates with bio-industry.
