If I only had a blastema: obstacles to human regeneration

Irv Weissman’s lab came out with a very intriguing paper in Nature this week on regeneration and something called a blastema.

Having a blastema

It is not exactly on regenerative medicine of the kind we think about using exogenous stem cells, but more about how we might tap into nature’s own program for regeneration by studying other “lower” organisms that make us seem very weak by comparison when we think of regenerative power.

An H&E stained blastema from NIH.

Many animals can regenerate parts of their bodies, particularly things that might get damaged say by a predator in everyday life.

A tail. A limb. A digit.

For humans, endogenous regeneration is fairly limited with the best, most robust example being the ability of the liver to regrow itself.

This particular paper was focused on digit regeneration in mice.

It turns out that mice have some very limited ability to regenerate their digits. They generally do not regrow an entire new “toe” if they lose one, but sometimes younger mice will regrow part of a toe.

How do blastema form and why can’t people make them?

For a long time the prevailing theory was that a very cool, yet poorly understood process of de-differentiation occurred to form a structure called the blastema that was integral to regeneration. In the studies from Weissman’s lab at least when it comes to mouse digit regeneration, it seems the role of the blastema and de-differentiation is most likely quite limited at the most. Instead, it appears that resident adult stem cells of different kinds play the dominant role in regrowing tissue.

This is a very interesting finding, but the story of limb regeneration is far from settled and there is fairly compelling evidence in other organisms that are studs when it comes to regeneration that the blastema does indeed play a crucial role.

Since humans do not seem to be able to regenerate digits or limbs at all, it is not clear how we might go about making this happen in people as a form of regenerative medicine and what regenerative organisms we might learn the best lessons from. Mice are of course more similar to people than are salamanders or fish, but those latter organisms that seem to undergo blastema-dependent regeneration are dramatically better at regeneration than mice are– so perhaps lessons from them can also help teach humans how to have a blast-ema and regrow digits and perhaps even limbs.

The other point from Irv’s paper is that maybe a blastema isn’t necessary and humans could regenerate digits or limbs with the transplantation of the right kind of stem cells. A very cool idea!