Regrowing Lost Limbs
quadclops
12 Feb 2007
REGROWING LOST LIMBS
Bouyed by recent genetic breakthroughs, researchers at Northwestern University and across the country have hopes of achieving a feat long thought to be impossible: enabling people to replace damaged body parts or even regrow missing limbs.
Like salamanders and other lower species, humans possess genes that direct the body to make new arms and legs after an injury. But in humans, the genes lie dormant, inactivated after evolution favored the swift patching of wounds through scarring over the slow regeneration of body parts.
The discoverer of those genetic switches, Northwestern developmental biologist Hans-Georg Simon, and other researchers think they can find a way to turn on the dormant genes. A person who lost a leg might be able to generate a new one.
"There are more species on Earth that can regenerate lost appendages than those that can't," Simon said. "We humans are more the exception." The idea is to explore what nature came up with in the first place and then try to find out what genes are inactivated in humans and try to reactivate them.
Pediatric surgeons were the first to witness the magical power of regeneration genes about 20 years ago when they began performing daring fetal surgery in early pregnancy. They were astonished to discover the fetus would later be born perfectly healed. No scars.
These same genes allow amphibian species such as alamanders to heal wounds without scars and to perfectly replace lost limbs throughout life. But in humans and other mammals, the genes get turned off shortly before birth.
"There is a transition in us humans where we go from a perfect wound healing phase through regeneration early on, to a later phase where scars begin to form," said Simon, who is working with Badylak's team. "That means we probably also possess the appropriate genes to perfectly heal wounds without scars. And that's the idea my colleagues and I have--to see if we can find the regeneration switch and reactivate it in humans."
Simon, who is also a cell and developmental biologist at Children's Memorial Research Institute, and his collleagues are genetically engineering mice to see if two genes can be turned on: Tbx5 for arms and Tbx4 for legs. They hope that within four years, they will have a mouse that can grow back a "finger."
Giving people the salamander's regenerative power has been one of science's oldest dreams, the U.S. military sought better ways to repair the disfiguring scars and amputated limbs that are occuring among soldiers in Afgahnistan and Iraq at the highest rate ever recorded during war.
The Research Projects Agency, or DARPA, looked at the scattered research going on in regeneration, concluded it could lead to something big and formed two teams of researchers with mulimillion dollar grants.
One team member may have already taken a step closer to a scar-less healing salve. Lorraine Gudas of the Weill Medical College of Cornell University discovered that vitamin A plays an important role in causing one type of cell to differentiate into other cell types, a critical step in regeneration. After a newt limb has been amputated, the amount of vitamin A it is exposed to, for example, will determine if the stump starts regenerating as a whole arm or as an elbow or wrist.
So promising has this line of research become that it is opening the door to "the next evolution of medical treatments," according to a new report, "2020: A New Vision--A Future for Regenerative Medicine," by the U.S. Department of Health and Human Services.
"Regenerative medicine, if driven by a cohesive federal initiative, has the opportunity to begin producing complex skin, cartilage and bone substitutes in as little as five years," it said. "Tissue and organ patches, designed to help regenerate damaged tissues and organs such as the heart and kidneys, are within reach in 10 years. Within 20 years, with appropriate federal funding and diraction, the goal of 'tissues on demand' is realistic."
The first regenerated bladders have already made a successful appearance. The bladders, made from a patient's own tissue, have functioned for five years in six patients, Wake Forest's Dr. Anthony Atala reported in april.
"Regenerative medicine definitely is the next generation of treatment, going from the hardware kind of medical devices to a living tissue that can grow and repair with the person," said Christine kelley, director of the division of discovery science and technology at the National Institute of Biomedical Imaging and Bioengineering.
Badylak said DARPA became interested in regenerative medicine because of the massive increase in the ratio of wounded military personnel. In all wars from the Revolutionary War up to the first Gulf War the ratio of wounded soldiers to those killed was 2.5 to 1. The 90's saw a dramatic change with the advent of body armor, which protected the torso and head but left arms, legs and neck exposed. In the Afghanistan and Iraq wars the ratio of wouned to dead is 9 to 1.
"They said let's look at something better than developing prosthetic limbs. Let's see if we can take it further," Badylak said. The two-year goal for the Badylak team is to have a mouse replicate the kind of biological transformation that occurs in a salamander at the site of an amputation called a blastema.
In a blastema, cells in the stump are converted into progenitor cells, which go on to make bone, skin, nerves and other structures that form a new limb. LIFE EXTENSION MAGAZINE.
