Gene and Stem Cell Therapy That Might Reverse Some of the Loss of Healing Capacity in the Elderly

One aspect of the frailty of being old is the loss of healing capacity. Stem cell activity diminishes, probably as a part of an evolved response to accumulated cellular damage that minimizes cancer risk, and even minor injuries become troubling. Researchers are investigating the details of this process with the intent of reversing the signaling systems involved, restoring some of the youthful ability to heal. This, unfortunately, doesn't do anything to address the underlying damage of aging - it is in some ways like removing the safety features that prevent overuse of a worn engine - but the end result is better than not having the ability to do this.

Researchers working with elderly mice have determined that combining gene therapy with an extra boost of the same stem cells the body already uses to repair itself leads to faster healing of burns and greater blood flow to the site of the wound. Their findings offer insight into why older people with burns fail to heal as well as younger patients, and how to potentially harness the power of the body's own bone marrow stem cells to reverse this age-related discrepancy.

To heal burns or other wounds, stem cells from the bone marrow rush into action, homing to the wound where they can become blood vessels, skin and other reparative tissue. The migration and homing of the stem cells is organized by a protein called Hypoxia-Inducible Factor-1 (HIF-1). In older people [fewer] of these stem cells are released from the bone marrow and there is a deficiency of HIF-1.

[Researchers] first attempted to boost the healing process in mice with burn wounds by increasing levels of HIF-1 using gene therapy, a process that included injecting the rodents with a better working copy of the gene that codes for the protein. That had worked to improve healing of wounds in diabetic animals, but the burn wound is particularly difficult to heal, and that approach was insufficient. So they supplemented the gene therapy by removing bone marrow from a young mouse and growing out the needed stem cells in the lab. When they had enough, they injected those supercharged cells back into the mice. After 17 days, there were significantly more mice with completely healed burns in the group treated with the combination therapy than in the other groups. The animals that got the combination therapy also showed better blood flow and more blood vessels supplying the wounds.



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