About Wound Healing

Are there stem cell therapies available for wound healing?

Currently, two therapies that use basal layer stem cell derived sheets for skin grafts have been approved for clinical use in Canada and the United States. They are mainly used for large burns where split thickness skin grafts are unavailable.

For the latest developments, read our blog entries here.

To find out about research underway at the University of Calgary to develop stem cell-based strategies to regenerate the skin and restore  function and appearance click here.

For more about stem cell clinical trials for wound healing click here. (For printed version: http://goo.gl/t2CWk)

How close are we? What do we know about wound healing?

  • Skin wounds happen for many reasons– injuries, cuts, burns, poor circulation, ulcers from pressure sores, illnesses such as diabetes, and genetic skin disorders.
  • When the inner layer of skin (dermis) is injured, the hair follicles and sweat glands in that layer may also be destroyed and repairing the top layer of skin becomes more difficult.
  • Age slows the healing process, possibly due to the weakening of the skin or compromised blood flow that may be the result of inactivity or external factors, such as smoking.
  • Skin grafts are the standard of care for serious wounds. Grafts can come from the patient (autograft) or from a donor (allograft). Autografts are ideal because they are an exact match. Allografts are used as a temporary covering of wounds, but are not a permanent treatment because the injured person’s body will eventually reject them.

How can stem cells play a part?

Currently, there are many challenges in treating acute and chronic wounds.  Some acute wounds, such as large burn injuries leave inadequate autologous donor tissue necessary to close the wound. In some chronic wounds, poor circulation may perpetuate a wound significantly. No conventional therapy can regenerate the middle dermis — crucial for rebuilding hair follicles, sweat glands and oil glands. Researchers are confident that stem cells — with their unparalleled regenerative capacity and the flexibility to grow into hundreds of different types of cells — can help.

Are there lots of groups working on developing a stem cell therapy?

Stem cells have been explored as therapies for wound healing for years by research teams around the globe. The challenge is to identify which stem cells are best suited for the job and which signals will be able to coax them into becoming all the components of the skin. Also, reliably growing and expanding stem cells for topical applications has been a challenge because it can take millions of cells to cover a larger area of skin.

Stem cell research for wound healing is moving along a number of different routes, some of which have been translated into early Phase 1 and 2 clinical trials. The majority of these are testing the safety of stem cells and the outlook is promising.

What research is underway?

Before basic stem cell research can be translated into the clinic for patients, it must be rigorously tested. For wound healing, this means grafting stem cells or their products onto animals to test if damaged skin can be restored. Some of the stem cells being considered are adult skin stem cells, mesenchymal stem cells, and pluripotent stem cells.

In most studies, stem cells are injected into the dermis or around the edge of the wound. Researchers are also testing whether stem cells applied topically in a spray or embedded in a scaffold or gel may work better.

The road to finding a stem cell therapy for wound healing is paved with many challenges that will take time to overcome. But the wealth of information generated from labs around the globe is converging to help with the transition from basic research to the clinic. The results are encouraging.

Current research using skin stem cells

Skin has many different types of stem cells, including epidermal stem cells, melanocyte stem cells (which make pigment-producing cells), and epithelial and mesenchymal stem cells that reside in hair follicles. These stem cells generate particular types of cells to perpetually renew healthy skin. Hair follicle stem cells and epithelial stem cells are also thought to interact with circulating bone marrow derived cells to bring about speedy wound closure and tissue repair.

Researchers are looking to tap into the built-in (endogenous) power of skin stem cells to repair wounds and are making some headway at the pre-clinical stage. For example, Canadian scientists are testing whether dermal stem cells that live in human hair follicles can be used to populate split thickness skin grafts, the main surgical procedure to repair deep burns and other wounds. They are also identifying drugs that can stimulate dermal stem cells — called skin-derived precursors, or SKPs — to speed up and improve  wound healing. Epithelial stem cells may also become an important source for generating new functional skin because they can make keratinocytes that form the epidermis (outer layer of skin) as well as hair follicles and glands that are crucial for normal function and appearance of the skin.

Clinical studies using skin stem cells are still in early stages, but they are helping to provide proof-of-concept for the possibility of using skin stem cells to treat wounds.

Current research using mesenchymal stem cells

Mesenchymal stem cells can make many different types of cells (including skin cells) and are very accessible: they are found in bone marrow, fat tissue, umbilical cords and dermal layers of the skin. These stem cells are easiest to harvest from the bone marrow and can then be grown in a dish for transplant. They can also modulate the immune response, helping transplanted cells avoid graft rejection. Small clinical trials have shown that mesenchymal stem cells from the bone marrow can help wounds to close better. These positive results have opened the door to larger trials.

Current research using pluripotent stem cells

Researchers have found a way to turn back the clock on adult cells and reprogram them to behave like embryonic stem cells. Called induced pluripotent stem cells or iPS cells, they can be made from a patient’s skin or other tissue cells. Cells made this way are compatible as skin grafts, but potential tumour formation from the viral components used to genetically reprogram them has been a barrier to widespread use. Scientists are working on safer methods that don’t involve genetic reprogramming.

Further reading on wound healing

Canadian Association of Wound Care (http://goo.gl/WJkBL)

Wound Care Canada (http://goo.gl/H0Xts)