In the United States, nearly 2 million adults (or 1 in every 200) suffer from loss of an arm, leg, foot or hand. Most major limb losses result from traumatic injury in accidents or military combat; or from disease conditions like bone tumors or diabetes. An additional 6 in every 10,000 children are born with missing limbs, or limb malformations so severe that the arm or leg is rendered nonfunctional. Amputees suffer from disabling mobility loss and disfiguring deformity, accompanied by adverse social and economic consequences for the patient and their family as well as significant health care and disability costs for society.
Humanity has pondered the possibility of human limb regeneration since at least the mid-1700s, when the ability of certain amphibians to regrow entire limbs was first scientifically demonstrated.
In fact, human limbs do have regenerative potential. Loss of the tip of the finger (or toe) is followed by a natural and spontaneous regeneration response that forms a complete replacement fingertip. However, this regenerative capacity is limited to digit tip. Limb or digit tissue lost past that point is not regenerated; instead, scar tissue forms at the injury site and replacement structures are not formed.
It is still not known why some animals can regenerate entire limbs, while humans and other mammals can only regenerate digit tips. If we knew the answer to this age-old question, the dream of biological limb replacement through regeneration could one day become a reality. The goal of our research is to better understand why some limb tissue has regenerative competency, and some does not.
This is an exciting time for regenerative medicine, as new evidence reveals that “stem cells” with hidden regenerative capacity are naturally present in many parts of the body. This argues against using donor stem cell transplants or injections, or orthopedically-engineered tissues, to repair or replace damaged or missing body parts. Rather, we may be able to use our knowledge of development and basic biology to “awaken” regenerative capacity by the body’s own cells, and to direct them to regenerate the needed tissue, organ, or in this case, limb.
In our research, we are using a mouse model to identify cells naturally present in the digit that have regenerative capacity, and we are identifying signals that stimulate them to participate in regenerative responses in otherwise non-regenerative digit tissue. Our findings support the tantalizing possibility that one day, clinical approaches could be developed to stimulate the body’s own natural potential to regenerate replacement limbs.
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