Regenerative Medicine and the Use of Stem Cells in Wound Healing

When I say the term, “regenerative”, it usually does not evoke the response it should, even when talking to physicians. Regeneration is not a vague, cliché, or sophisticated medical term. It specifically refers to the replacement of damaged tissue or organs with genetically identical tissue. This does not occur in humans and we don’t heal this way (except in a fetus less than 12 weeks old under certain circumstances). Humans heal by the development of scar tissue. This is very different from the original tissue. It is normally quite functional, but in certain circumstances can create further disease. This is the case of intra-abdominal adhesions caused by healing after surgery with internal scar. Scar formation is an inflammatory process that begins at the time of injury to a tissue. The formation of scar is a complex cascade of physiologic events resulting in healing. It is one of the great miracles of life (Chai). Again, at times it can be problematic.

To see an example of regenerative healing in the animal kingdom you need to slide down the genetic tree of life to reptiles, more specifically the salamander. This animal can lose its tail or a limb and have it “regenerate” (grow back). Another example is one of my favorite delicacies, the stone crab. His tasty dominant claw is removed, and the creature is returned to the sea, the great test tube of life, where he regenerates (grows) a genetically identical claw.

OK. You get the picture. In a wound, healed by regenerative techniques, the wound does not heal by scar but rather it heals regeneratively, with the same tissue that was destroyed. For most wounds the tissue is skeletal muscle. That is, a full thickness wound extending from directly beneath the skin down to bone, the loss of tissue is replaced with muscle, not scar. When used intraoperatively, adhesions, biliary leaks, strictures and many other complications of surgery can be prevented.

We use this technique to heal complicated wounds that are large and or difficult to heal. Using products to accomplish this treatment, we can heal wounds that previously could not be healed and heal other wounds in a fraction of the time that it would normally take. Reduced healing time along with the obvious benefits reduces recurrent infections and other chronic wound complications, thus reducing hospitalizations and amputations.

The products we use are often referred to as skin substitutes. There are likely 20 products or more on the market. These products are derived from many different organs from many different animals. All these products share two specific qualities. They all are derived from the basement membrane of the organ in question and they are acellular. That is, they contain no living cells. In the Hospital we use “Acellular Xenograft” (derived from pig bladder), while outpatient, we use Epifix grafts (from human placenta).

These products work by mobilizing the patient’s own circulating stem cells. Humans produce stem cells throughout life. The product is a graft which is placed over the wound in contact with the wound base. Stem cells are attracted to the graft implanting in the wound base. In the case of our patients the stem cells differentiate into skeletal muscle. When grafts are placed on other organs, stem cells differentiate into whatever the native tissue is.

Currently, there are two approved indications for this treatment in wound care. 1. Diabetic lower extremity wounds. 2. Lower extremity venous wounds. We use them in the hospital setting for a third indication. That is, for full thickness pressure ulcers. As this is not a reimbursable diagnosis the hospital provides the graft free of charge to give these difficult wounds the best chance of healing. We are hoping to undertake a study in the near future to prove the efficacy of this intervention in this type of previously un-studied wound. Armed with good clinical data, we hope to get these products approved for previously non-approved indications making them available to more patients.

Regeneration is the future of wound care and beyond. It is hope for spinal cord injuries and a host of other debilitating afflictions.