Whole-body Induced Cell Turnover: The Future Of Cell Therapy?

Discounting your bacterial companions you contain around 37.2 trillion cells, and over the course of a lifetime growing numbers become gradually compromised, mutated or damaged by the aging process. While some aging researchers aspire to prevent aging from happening in the first place, for that to happen we need to understand the process itself in detail. At present we still have more of a rough outline than an understanding.

An intestinal 'organoid', or mini organ grown from stem cells Credit: St Johnston D

While curious minded people might like to understand exactly why something happens, there are many examples where you don't have to understand everything that's going on to fix the problem. After all, your average car might break down every few years but by replacing the parts you can keep it going for decades; you don't have to redesign the car so it never breaks down again. This is where reparative strategies come in, aiming to rejuvenate and repair accumulated damage. These strategies are immensely challenging, but in comparison to an overhaul of the human genome, they're arguably easier to implement and we're already working on many of the tools that would be needed.

Out with the old, in with the new

Proposed by Francesco Cortese from the ELPIs Foundation for Indefinite Lifespans and Dr. Giovanni Santostasi, from the Feinberg School of Medicine, Northwestern University, WICT (Whole-body Induced Cell Turnover ) is a comprehensive strategy that involves replacing your entire body with shiny new cells, flushing the body of any old, damaged ones.

How would it work?

The WICT strategy involves a gradual, targeted destruction of your entire body in multiple rounds. After each round, new cells would be administered that match those removed in both type and quantity. These could be grown using a number of methods, including use of induced pluripotent stem cells derived from the patient themselves.

The targeted removal method outlined is a delivery of suicide genes to the particular area by cell type specific vectors. Vectors today range from modified viruses to liposomes, and in this case each vector would need to be designed to deliver the suicide package to a specific set of cells - producing carefully controlled cell death.

Why is this a good idea?

Viral vectors are one method of delivering genetic material into cells

It means you don't have to fix everything, you can replace it instead. Accumulated issues like telomere loss, mitochondrial mutations, genomic mutations, epigenetic changes and clumps of aggregates clogging up the cell are complex problems. This sort of approach would be undoubtedly challenging to implement, but it has an appealing simplicity about it. Because each issue takes some time to arise, periodic cell replacement could give you a new window of time in each area; gifting people with more time while we perfect new strategies.

Growing cells in the lab also gives you a carefully controlled environment, enabling you to monitor any mutations for example. Under stringent controls, the new cell populations could be as good as new, with any undesirables sieved out.

What are the risks?

In the paper the authors address some concerns with the procedure, like risk of cancer, poor efficiency, risk of new cells going where they shouldn't and many more. These are admittedly significant hurdles, and some organs may be particularly difficult or unsuitable for this process.

Is it possible?

The detail required means that the entire procedure would not be possible with today's technological know-how. It may require significant investment and advancement in cell and gene therapy fields, but adoption of aspects of this proposal could work excellently on a smaller scale too. We're getting better at growing new organs in the laboratory all the time, and organ transplantation must have seemed peculiar when it was first trialled, so perhaps Whole-body induced cell turnover is simply the logical next step in the pursuit of longevity and health.

The proposed strategy will appear in Rejuvenation Research, and was authored by Francesco Cortese from the ELPIs Foundation for Indefinite Lifespans and Dr. Giovanni Santostasi, from the Feinberg School of Medicine, Northwestern University. You can find the paper here