Regenerating Tissue By Reprogramming Cells

Image courtesy of Christina Tu / Sue & Bill Gross Stem Cell Research Center.

Many of the biggest issues in medicine today are caused by diseases in which damage is largely irreversible under normal conditions; in diabetes sufferers the body fails to replenish lost pancreatic cells and in Parkinson’s dopaminergic neurons are lost without replacement. Whilst one route to treating these is through stem cell transplantation, another may be to directly reprogram healthy cells in a particular area – effectively telling them to act like stem cells and repair tissue themselves.  

The majority of cells in the body have the same raw genetic code inside them but it’s regulated differently, which produces the enormous range in our bodies. This regulation and specialization is normally a good thing, one example being cells that are exposed to damaging environments (like our skin or gut) being replenished by niches somewhat protected from damage themselves. This makes it harder for damaged cells to cause problems if they’re being sloughed off continuously. If every cell had total regenerative capacity all the time, then it would create a lot more problems than it solved. With this being said, humans don’t have the regenerative capacity many of us would like and scientists have been trying to work out how to improve it when needed. 

Whilst various stem cell routes are one option, another viable alternative might be something called ‘direct reprogramming‘, which involves telling healthy, non-stem cell types to behave differently and replenish lost tissue. When embryonic stem cells are formed naturally after fertilisation, those cells undergo epigenetic reprogramming, essentially wiping the slate clean so a whole new person can be created from scratch. As we understand more of how this is accomplished, we can learn how to reprogram cells directly, instead of having to act through stem cell sources all the time. Induced pluripotent stem cells are an example of this, turning your own cells into new sources of stem cells to be used. Direct reprogramming differs from this in that instead of creating stem cells first, it aims to tell cells to change straight into more specialized varieties (like lung or heart cells), skipping the stem cell step entirely. 

This method, as described in this paper, reduces the risk of leftover stem cells doing things we don’t want them to. It can also be done inside the body, instead of having to take a sample, make it into stem cells and then put it back in the patient as occurs in most stem cell therapy. There is currently a lot of development going on in the subject, including research on replenishing cardiovascular pacemaker cells and insulin producing cells normally lost in type 1 diabetes. There is also a clinical trial testing if direct reprogramming can repair deafness.

Clearly there are a great deal of hurdles to overcome, such as how to deliver these chemical signals to only the desired area (so you don’t end up with things like ear cells in the wrong place), but it could prove to be another promising route in regenerative medicine. 

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