Led by Dr. Frank Isik, scientists from the University of Washington have recently demonstrated a totally novel method by which bone marrow contributes to the process of wound healing and repair. Bone marrow cells, like embryonic cells, are classified as stem cells, meaning that they have the potential to develop into a wide variety of other cells. Under certain circumstances, such as an injury or wound, signals are released to cause bone marrow cells to develop into a particular type of cell. These new cells are then referred to as “bone marrow-derived” cells.
It is well established that during the first stages of wound recovery (healing), there is a mobilization of bone marrow-derived cells that prevents infection and commences the healing process. However, once this early, acute stage was finished, most of these cells were believed to die off or move back into general circulation. On the contrary, Isik et al demonstrate that a previously unidentified subset of bone marrow-derived cells play a very critical role during the secondary healing/restructuring process. Notably, these cells have been shown to be capable of producing type III collagen, a structural protein that is critical to regeneration and ultimate repair of a wound.
The University of Washington team made this discovery largely because they chose a new way of identifying bone marrow-derived cells. Traditionally, scientists have tracked bone marrow-derived cells at wound sites by searching for the presence of CD45 or CD34. CD45 and CD34 are proteins present on the surface of many bone marrow-derived cells involved in the initial inflammatory response. However, instead of following either of these proteins, known to be present on the bone marrow-derived cells (in other words by tracking the end product), the group actually inserted a green fluorescent protein (GFP) marker at the original, undifferentiated bone marrow cells (i.e. the source). This was accomplished by transplanting bone marrow from mice with all cells possessing the GFP marker into mice lacking GFP, but that were otherwise genetically identical.
As a result of using this different methodology, Isik and colleagues identified the existence of bone marrow-derived cells (end products) that were GFP positive (+) with CD45 markings (+), and unexpectedly, those that were GFP(+) without CD45 markings (-). These GFP(+) and CD45(-) cells were found to be present at stable levels in normal, uninjured skin. At a wound site, during the initial stages of healing almost all bone marrow-derived cells were GFP(+) and CD45(+), confirming conventional wisdom. During the latter phases of wound regeneration and repair however, the percentage of GFP(+) and CD45(-) increases at the wound site during tissue remodeling. All bone marrow-derived cells, whether CD45 (+) or (-), were shown to produce type III collagen, while “regular” cells did not. Thus, the continued presence of bone marrow-derived cells in the latter stages of wound repair may be largely to produce type III collagen for the regenerative process.
This novel role for bone marrow-derived cells may in turn lead to new approaches for treating serious or chronic wounds.
SOURCES
• Fathke C, Wilson L, Hutter J, Kapoor V, Smith A, Hocking A, Isik F. Contribution of Bone Marrow-Derived Cells to Skin: Collagen Deposition and Wound Repair. Stem Cells. 2004; 22(5):812-22.
• Neary, Walter. Bone marrow cells routinely help with wound healing. University of Washington. Press Release, September 3, 2004.
Last updated: 07-Oct-04
