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Backwards progress? Skeletal stem cells turn back time to correct damage

Is extensive regeneration possible in humans? Stanford researchers show skeletal stem cells can move backward developmentally when major repairs are needed.

I've recently written here about the research tour de force that led to the identification of the human and mouse skeletal stem cell. These cells can generate bone, cartilage and the bone's spongy interior during development and spring into action to repair fractures.

Now researchers from the same lab, headed by regenerative medicine specialist and reconstructive surgeon Michael Longaker, MD, along with others from the lab of stem cell scientist Howard Chang, MD, PhD, have learned that, when tasked with extensive repair jobs, these cells do something absolutely fascinating: they turn back developmental time to become even more developmentally flexible  (I'm imagining Hermione's clever use of a Time-Turner in the third book of the Harry Potter series, although I guess channeling a little Cher would not be inappropriate here).

Chang and Longaker, together with graduate students Ava Carter and Ryan Ransom, published their results recently in Nature.

As I describe in our release:

The results suggest the possibility of using naturally occurring adult stem cells, which are usually restricted to generating only a limited panel of closely related progeny, to carry out more extensive regeneration projects throughout the body — much in the way that salamanders or newts can replace entire limbs or tails.

The researchers were studying how skeletal stem cells in mice react to a common surgical procedure called distraction osteogenesis often used in infants to correct under or malformed jaw bones called mandibles. During distraction osteogenesis, the bone is surgically fractured, and an adjustable device is inserted to gradually increase the distance between the ends of the bone over time. This encourages new bone growth to fill in the gap and create what resembles a normally developed mandible. But exactly how the skeletal stem cell accomplish this has been unknown.

In this study, the researchers learned that the skeletal stem cells assume characteristics of cranial neural crest cells that, in humans, originate five or six weeks after conception. During development, cranial neural cells then migrate from the area that eventually becomes the spinal cord to form the head and face. As part of this process, they also give rise to skeletal stem cells. The potential clinical implications of the cells' march backward through developmental time are intriguing.

As Longaker said:

It’s pretty remarkable that this would happen in an adult animal...

This is an opportunity to change how we think about the development of not just the skeleton, but also other tissues and organs. Can we go back in time after an organ is formed to trigger more extensive regeneration? This at least opens the door to that possibility.”

Photo by lozikiki

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