The Mace Lab
Regulation of adult stem cells in response to injury
Adult stem cells reside in a variety of niches, including the bone marrow. Bone marrow-derived cells (BMDCs) contain a subpopulation of multipotent stem cells that can migrate to peripheral tissues and, once there, differentiate and contribute to the maintenance of that tissue. BMDCs also appear to play an extensive role in repair and regeneration. For example, in skin, a small number of BMDCs routinely migrate to the dermis and contribute to many resident cell populations. This process is dramatically 'ramped up' in response to injury, and then returns to normal as wound healing resolves and homeostasis is achieved.
Previously we demonstrated that the transcription factor, Hoxa3, significantly promotes angiogenesis during tissue repair and regeneration (Mace et al., 2005 J Cell Sci). Subsequent analysis of GFP bone marrow chimeras during wound repair in mice with attenuated Hoxa3 expression revealed that Hoxa3 can modulate the recruitment of different bone marrow-derived cell (BMDC) types to the site of injury. For example, directed Hoxa3 expression in the wound promotes the recruitment of endothelial progenitor cells, while reducing the number of inflammatory cells recruited (Mace et al., 2009 Stem Cells). The balance of different BMDC types present in the injured tissue can profoundly affect the repair and regeneration process.
The current aims of the lab include (1) understanding how signals from the injured tissue affect the behaviour of adult stem cells, (2) determining how these signals change over time and in different wound environments, such as diabetic chronic wounds, and (3) developing techniques to manipulate the behaviour of adult stem cells in vivo to improve wound healing, particularly in the chronic wound environment.
Latest Publications
Mahdipour, E., Charnock, JC. and Mace, KA. (2011) Hoxa3 promotes the differentiation of haematopoietic progenitor cells into proangiogenic Gr-1+CD11b+ myeloid cells. Blood 117(3): 815-826.
PubMed entry PMID:20974673
Restivo, TE., Mace, KA., Harken, AH. and Young, DM. (2010) Application of the chemokine CXCL12 expression plasmid restores wound healing to near normal in a diabetic mouse model. J Trauma 69(2):392-398.
PubMed entry PMID:20699749
Landry, Y., Le, O., Restivo, TE., Mace, KA., and Beausejour, CM. (2010) Secretion of SDF-1alpha by bone marrow-derived stromal cells enhances skin wound healing of C57BL/6 mice exposed to ionizing radiation. J Cell Mol Med 14(6B):1594-1604.
PubMed entry PMID:19725920
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