Scientists have unveiled a breakthrough method known as “transient-naive-treatment” (TNT) reprogramming that facilitates the transformation of human cells to closely mirror embryonic stem cells, offering solutions to a chronic problem in regenerative medicine. This pioneering technique sets new standards for both research and therapeutic cellular treatments.
The Australian research team, led by Professor Ryan Lister from the Harry Perkins Institute of Medical Research and The University of Western Australia, as well as Professor Jose M Polo from Monash University and the University of Adelaide, has developed this new technique that has substantial implications for the field of biomedical therapy.
This novel approach addresses the challenges that arose from a revolutionary discovery in the mid-2000s, where it was found that adult ‘somatic’ cells could be artificially altered into a state resembling embryonic stem (ES) cells, capable of forming any body cell. While this offered a seemingly unlimited supply of ES-like cells for use in applications like disease modeling, drug screening, and cell therapies, conventional reprogramming methods were flawed. These induced pluripotent stem (iPS) cells would often keep an epigenetic memory of their initial state, creating discrepancies between the iPS and ES cells, limiting their practical use.
The TNT reprogramming method, explained by Professor Polo and colleagues, imitates the resetting process of a cell’s epigenome occurring in early embryonic development, minimizing differences between iPS and ES cells. This enhances the way human iPS cells can be employed.
The researchers, including Dr. Sam Buckberry and Dr. Xiaodong Liu, studied the process of epigenome transformation throughout reprogramming to detect when aberrations emerged. They then introduced a new reset step to erase these discrepancies and the memory, producing human TNT-iPS cells that more closely match human ES cells, both functionally and molecularly.
This new method, praised as “dynamite” by team member Jia Tan, leads to better differentiation into various cells, like neuron progenitors, compared to standard methods. The innovation addresses key issues with traditional iPS cells, preventing potential long-term detrimental effects for cell therapies.
The precise molecular mechanisms involved in the iPS epigenome issues and their correction remain somewhat obscure, calling for further investigation. Still, Professors Lister and Polo forecast that the TNT reprogramming method will form a new standard in cell therapies and biomedical research, contributing substantially to their ongoing advancement.
This significant research effort involved collaboration with scholars from various universities and institutes across Australia, London, and other global locations. The study was published in the journal Nature on August 16, 2023.
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Frequently Asked Questions (FAQs) about TNT reprogramming
What is the TNT reprogramming method?
The TNT (transient-naive-treatment) reprogramming method is a revolutionary technique developed by Australian scientists that allows human cells to be reprogrammed to closely resemble embryonic stem cells. This method addresses a longstanding issue in regenerative medicine, reducing the differences between induced pluripotent stem (iPS) cells and embryonic stem (ES) cells, thereby enhancing their applications in disease modeling, drug screening, and cell-based therapies.
Who led the research team for the TNT reprogramming method?
The research team for the TNT reprogramming method was led by Professor Ryan Lister from the Harry Perkins Institute of Medical Research and The University of Western Australia, and Professor Jose M Polo from Monash University and the University of Adelaide.
How does the TNT reprogramming method improve existing cell reprogramming techniques?
The TNT reprogramming method improves existing techniques by mimicking the reset of a cell’s epigenome that happens in early embryonic development. This minimizes the functional differences between iPS cells and ES cells and maximizes their effectiveness in various applications. Conventional methods often result in iPS cells retaining an epigenetic memory of their original state, limiting their use, a problem that the TNT method overcomes.
What are the potential applications of the TNT reprogramming method?
The TNT reprogramming method offers significant potential in regenerative medicine. It provides a way to create a virtually unlimited supply of cells resembling embryonic stem cells, which can be used for disease modeling, drug screening, and cell-based therapies. It also sets new standards for research in these fields.
What challenges does the TNT reprogramming method resolve?
The TNT reprogramming method resolves the persistent problem of iPS cells retaining an epigenetic memory of their original somatic state, along with other epigenetic abnormalities. This has previously created functional differences between iPS cells and ES cells, limiting their usability. By introducing a new epigenome reset step to erase these differences and the cellular memory, the TNT method overcomes these challenges.
More about TNT reprogramming
- Nature Journal
- Harry Perkins Institute of Medical Research
- Monash University
- The University of Western Australia
- University of Adelaide
