New stem cell method produces millions of human brain and muscle cells in days

The new platform technology, OPTi-OX, optimises the way of switching on genes in human stem cells

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

Notes to Editors
Publications
  • Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes.

    Pawlowski M, Ortmann D, Bertero A, Tavares JM, Pedersen RA et al.

    Stem cell reports 2017;8;4;803-812

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.

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