Recent work at King’s College London and Osaka University, Japan has shown that bone marrow stem cells can differentiate into mature skin cells and repair damaged skin. This finding could provide a remarkable benefit to people with chronic wounds like leg ulcers, burns and pressure sores. Likewise, victims of genetic diseases that affect the skin like epidermolysis bullosa, which causes painful blisters on the skin, might also be treatable with this procedure.
These scientists took advantage of the finding that bone marrow probably plays a role in skin wound healing. However, this work makes it clear that specific bone marrow stem cells are involved in wound healing, and this work also identified the specific triggers that recruit these particular skin cells to the affected skin area.
These research teams examines mice with skin damage and compared the healing mechanisms involved when skin grafts are used, compared with those mechanisms used in non-grafted wound healing. The findings showed that in mice with non-grafted wound healing, very few bone marrow cells traveled to the wound to repair it and did not make a major contribution to epidermal repair. However in mice where a skin graft was used, a significantly higher number of specific bone marrow-derived cells traveled to the skin graft to heal the area more quickly and build new skin directly from the bone marrow cells.
Amazingly, the research showed that around one in every 450 bone marrow cells has the capacity to become a skin cell and regenerate the skin. Also, the trigger that recruits the bone marrow cells to repair skin is a protein called HMGB1, which is made by damaged skin. HMGB1 mobilizes the cells from bone marrow and directs them to where they need to go to heal the damage. Mice with skin grafts express high levels of HMGB1 in their blood, and this protein drives the bone marrow repair process. These findings provide new insight into how skin grafts work in medicine. They do not simply cover wounds; instead they act as bioreactors that potentially kick-start regenerative skin repair.
Patients who suffer from the genetic disease epidermolysis bullosa also express high levels of HMGB1 in their blood. Furthermore, the source of this HMGB1 is the roofs of the blisters in their skin. This demonstrates that HMGB1 is also important in human skin damage and wound healing responses.
John McGrath, leader of the Genetic Skin Disease Group at King’s College said, “This work is tremendously exciting for the field of regenerative medicine. The key achievement has been to find out which bone marrow cells can transform into skin cells and repair and maintain the skin as healthy tissue, and to learn how this process happens. . . Understanding how the protein HMGB1 works as a distress signal to summon these particular bone marrow cells is expected to have significant implications for clinical medicine, and could potentially revolutionize the management of wound healing.”
McGrath is working together with colleagues at Osaka Univ. to harness the key parts of the HMGB1 protein to create a drug treatment that can augment tissue repair. Clinical trials that test this treatment protocol in humans rather than animal models is a distinct probability. This research was published in the journal in Proceedings of the National Academy of Sciences.