Commanding cells to regenereate a body part.

[Evangelante]

Would it be possible to command the the human body to have a certain part of the body regenerated? I've been wondering about this for quite some time. I wonder if there is some type of programming within cells that could be altered or perhaps a configuration within other parts of the body that could be altered to command cells to recreate or remake another body part.

 

Let's say the eye for instance. The eye get damaged and you become blind in it. Is there a way to command cells to regenerate tissue and muscles?

[Bluenoise]

Possibly with the right combination of stem cells and developmental factors. But you should know that when a body part first divelopes it is acting on cues and signals from other nearby parts that are in specific stages of developement. Mimmicing these in an already developed human body to regenerate a whole organ would be very tricky to say the least.

[Mokele]

Well, it *can* occur in vertebrates, most notably the axlotl salamander (a neotenic form of the common American genus Ambystoma), so it's possible in principle. There's probably some pretty strong biological and biochemical hurdles to cross before we get there, though.

 

Mokele

[rakuenso]

I wonder why whatever the genes responsible to constant regeneration was turned off in the first place? What evolutionary advantages were there? Decreased chance of cancer?

[Mokele]

I wonder why whatever the genes responsible to constant regeneration was turned off in the first place? What evolutionary advantages were there? Decreased chance of cancer?

 

Possibly, but my bet would be that increased tissue specialization and complexity are what got in the way. That the only salamander which can really regenerate perfectly is a very neotenic species (meaning it retains the juvenile form of the genus to adulthood) supports this, I feel.

 

It also might have something to do with the nervous system, since one of my labmates used to work with them, and mentioned that they can only regenerate if the nerve is intact relatively close to the wound.

 

Mokele

[newty]

Most urodeles (salamanders and newts) have the capability to regenerate major structures and organs, although the degree of regeneration differs among species. The most common model organisms are the red-spotted newt (Notophthalmus viridescens) and the axolotl. They can regenerate lens, retina, limbs, jaw, and most organs, etc. What they cannot regenerate is the underlying tissues that flank the regeneration-competent structures. For example, they cannot regenerate muscle that flanks their forelimbs.

 

What seperates animals that can regenerate from those who cannot. That is a big debate within the regenerative community. The short answer is that no one really knows. The long answer is that they think there are a lot of other factors, including a couple mentioned above. I will briefly list them: increased complexity (although this is only true up to a limited state in my opinion), occurence of cancer, immunological differences, genetic differences, and competency within cells.

 

There are examples of regeneration outside of urodeles. There is a mouse model where the mice can regenerate ears and limbs. It was serependitically discovered because they original authors were studying some other gene (transgenic mouse model here), and they could not keep track of the litters with the ear punching method. Humans can regenreate the liver (although this is not true regeneration). Human children, up to a certain age can regenerate the tips of their fingers upon amputation, provided that the wound is not attended to by hospitalization (e.g., cauterized, skin flap pulled over the wound, etc). Chickens can regenerate eyes, too. Zebrafish can regenerate eyes and fins. African frogs can regenerate their structures, but only int he premetamorphic phase.

 

Now, there are some studies otu there that have shown that adding certain factors can cause the occurence of regeneration. You see, in order for regeneration to occur, you need breakdown of the differentiated cells (a process called dedifferentiation), proliferatiion of these cells and redifferentiation to repopulate the missing appendage/organ. So, you need cues that break down cell-cell and cell-matrix environments, need cues to cause these cells to revert to an 'embryonic'-like state (lose their specialized cytoplasmic characteristics), cues to cause proliferation, cues to regulate migration, cues to cease proliferation, cues to intitiate redifferentiation and so on. There have been some factors that can cause the occurence of dedifferentiation (probably may be the most imporatnt step of regeneration - but each step is important anyways) including thrombin and msx1. If you do a Pubmed search of these with regeneration, you can find the original articles.

 

If you have any other questions, let me know.

 

Newty.

[rakuenso]

Possibly' date=' but my bet would be that increased tissue specialization and complexity are what got in the way. That the only salamander which can really regenerate perfectly is a very neotenic species (meaning it retains the juvenile form of the genus to adulthood) supports this, I feel.

 

It also might have something to do with the nervous system, since one of my labmates used to work with them, and mentioned that they can only regenerate if the nerve is intact relatively close to the wound.

 

Mokele[/quote']

 

speaking of which... i remember reading articles a while ago that claims scarring actually impedes the process of tissue regeneration. As to its exact biochemical impediments, I have no clue.

 

 

But if we were able to synthesize a compound that inhibits scarring, it might lead to some regenerative capabilities in the future. But it would have to be delicately worked in conjunction with blood clotting as well I imagine

[newty]

speaking of which... i remember reading articles a while ago that claims scarring actually impedes the process of tissue regeneration. As to its exact biochemical impediments' date=' I have no clue.

 

 

But if we were able to synthesize a compound that inhibits scarring, it might lead to some regenerative capabilities in the future. But it would have to be delicately worked in conjunction with blood clotting as well I imagine[/quote']

 

 

Yes, scarring is one of the major factors. As with children that can regenerate their fingertips, the important thing is to leave it alone and do not cause scarring. It is a well-covered topic in the medical sciences, but is not somethign that doctors leave alone.

 

One aspect that separates newts from mammals is the inflammatory response and the covering of the wound stump. Within 24 hours, the wound is covered by migration of neighbouring epithelial cells. This sets the basis of regeneration. If the newt doesnt have this, then regeneration is impaired. But, if you do amputate the limb proximally to this site and allow regeneration to occur, the newt regenerates the structure completely.

 

To prevent scarring, obviously as you are aware, it is not that simple. Scarring in mammals is a hugely complex process that involves the inflammatory response, coagulation cascade, immune system, etc. The factors may already be there in the mammalian system (e.g., thrombin), but it may be refractory to such signals for whatever reason. Nevertheless, it is a good idea to look for substances where we can modulate scarring to a certain degree.

 

Newty