Regenerative Medicine: Human Cells Have “Memory” Wiped

Regenerative Medicine: Human Cells Have “Memory” Wiped

iPS cells are a specific kind of pluripotent cell that can be produced by reprogramming mature human adult cells, also known as “somatic” cells. By doing so, they can become similar to embryonic stem cells, which means they have the ability to develop into any type of cell in the human body.

These cells were first discovered in 2006, and they have many potential medical and therapeutic applications, such as simulating diseases, testing drugs, and using cell-based treatments.

The discovery of these cells dates back to 2006

Despite their potential, researchers have faced a major obstacle that has prevented iPS cells from fulfilling their potential.

“A persistent problem with the conventional reprograming process is that iPS cells can retain an epigenetic memory of their original somatic state, as well as other epigenetic abnormalities,” Professor Ryan Lister, lead author of a paper presenting the latest breakthrough, said in a statement.

“This can create functional differences between the iPS cells and the [embryonic stem] cells they’re supposed to imitate, and specialised cells subsequently derived from them, which limits their use.”

Luckily, Lister and his team have developed a solution to overcome this issue. They have introduced a new technique, known as transient-naïve-treatment (TNT) reprogramming, which imitates the epigenome reset that occurs during the initial stages of embryonic growth.

This method has enabled them to generate iPS cells that resemble and function similarly to embryonic stem cells, with minimal discrepancies between the two.

“It solves problems associated with conventionally generated iPS cells that if not addressed could have severely detrimental consequences for cell therapies in the long run,” co-first author Jia Tan said of the potential impact of their work.

Dr Sam Buckberry, Tan’s co-author, elaborated on how their team accomplished a remarkable achievement. They began by examining changes in the somatic cell epigenome that took place during reprogramming, and then identified the moment when epigenetic abnormalities appeared (happening midway through reprogramming).

They then introduced a new epigenome reset step to prevent this issue from occurring. Using this approach, they generated TNT-iPS cells that could differentiate into various cell types, such as cortical neurons, skeletal muscle cells, and lung epithelial cells, surpassing the results obtained through the standard method.

“TNT reprogramming corrects epigenetic memory and aberrations, producing [iPS] cells that are molecularly and functionally more similar to [embryonic stem] cells than conventional [iPS] cells,” the study authors write.

“We foresee TNT reprogramming becoming a new standard for biomedical and therapeutic applications and providing a novel system for studying epigenetic memory.”

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