A suspension of muscle progenitor cells is injected into the cell-free matrix of a decellularized rat limb, which provides shape and structure onto which regenerated tissue can grow. Image credit: Bernhard Jank, MD/ Ott Laboratory

Many of us take our bodies for granted. Going for a jog or writing a letter to a friend doesn’t give us a moment’s pause. However, there are a number of individuals for who these things are a daily struggle. In the United States alone, there are an estimated 1.5 to 2 million people living with limb-loss. Each year, some 185,000 amputations occur across the States.

But now, science is bringing new hope to those who have lost a limb.

Harald Ott is a thoracic surgeon at Massachusetts General Hospital, and he just made the world’s first lab-grown limb. That’s right. This past week (02 June 2015), the hospital announced that Ott and his team successfully made a living, functioning, artificial leg that responds to stimuli and even circulates blood. What’s more, in the paper, which was published in the journal Biomaterials, the scientists showed evidence that these same techniques could be applied to the limbs of primates.

Of course, our bodies (and the bodies of other living organisms) are terribly complex. As such, this feat only comes as the result of years of study. Previously, doctors had successful completed hand transplants and other, similar operations. However, such treatments generally required life-long immunosuppressive therapy (this therapy suppresses the individual’s immune system in order to ensure that the body does not reject the transplant).

Ultimately, we were missing the matrix (scaffold) on which cells could grow into the appropriate tissues (namely, a  way to populate a limb with specific cells from an individual ).

But no longer: “Limbs contain muscles, bone, cartilage, blood vessels, tendons, ligaments and nerves – each of which has to be rebuilt and requires a specific supporting structure called the matrix,” Ott noted in the press release. “We have shown that we can maintain the matrix of all of these tissues in their natural relationships to each other, that we can culture the entire construct over prolonged periods of time, and that we can repopulate the vascular system and musculature.”

For the process, living cells are taken out of a donor organ. A detergent solution is used in order to facilitate this process. The remaining matrix (the non-living limb that remains) is then “repopulated” with progenitor cells (cells that, in the same way as stem cells, have a tendency to develop into a specific type of cell) that are appropriate to the specific organ. In essence, the doctors implanted the cells that make up blood vessels and muscles into the scaffold.

For this particular attempt, the  forelimb of a deceased rat was used, and after the removal of cellular debris, a “cell-free matrix” remained that provided a structure to all of a limb’s composite tissues (meaning that the bones and cartilage were missing).

After the re-population process was completed, tests were done to determine the effectiveness of the methods. An analysis of the limb confirmed the presence of vascular cells. Moreover, they confirmed that blood vessel walls and muscle cells aligned into appropriate fibers throughout the muscle matrix. The paper notes that function rates were high, “functional testing of the isolated limbs showed that electrical stimulation of muscle fibers caused them to contract with a strength 80 percent of what would be seen in newborn animals.”

Similar work has previously been done with a number of organs, such as kidneys and hearts, but this is the first case of engineering the more complex tissues of a bioartificial limb.

The next step will be to work on reintegrating the limb into the nervous system. “In clinical limb transplantation, nerves do grow back into the graft,  enabling both motion and sensation, and we have learned that this process is largely guided by the nerve matrix within the graft. We hope in future work to show that the same will apply to bioartificial grafts.  Additional next steps will be replicating our success in muscle regeneration with human cells and expanding that to other tissue types, such as bone, cartilage and connective tissue,” Ott asserts.

That said, we are still some ways away from providing individuals with usable limbs, but we just took a notable step forward.

WATCH: Making a Limb

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