Bone marrow-derived keratinocytes are not detected in normal skin and only rarely detected in wounded skin in two different murine models

Objective: Because the ability of bone marrow-derived cells (BMDCs) to repopulate tissues and the possible mechanisms of repopulation remain controversial, we used two distinct murine models to determine whether BMDCs can repopulate epidermal keratinocytes during either steady-state homeostasis or after tissue injury. Methods: The accessibility of skin keratinocytes makes it an excellent tissue to assess BMDC repopulation. In the two murine models, BMDCs from either male homologous B6, 129S Rosa26 mice that constitutively express ß-galactosidase or male hemizygote C57 BL/6-Tg(ACTbEGFP)1Osb/J mice expressing enhanced green fluorescent protein were transplanted via tail vein injection into control lethally irradiated (9.5 Gy) congenic female recipients and the percentage of keratinocytes derived from the transplanted BMDCs, both with and without wounding, was carefully determined. Results: Analysis of bone marrow, thymus, spleen, and lymph nodes confirmed complete engraftment of donor BMDCs 6 months post-bone marrow transplantation. However, during steady-state homeostasis, bone marrow-derived keratinocytes could not be detected in the epidermis. In a skin wound-healing model, the epidermis contained only rare bone marrow-derived keratinocytes (<0.0001%) but did contain scattered bone marrow-derived Langerhans cells. Conclusions: These results suggest that BMDCs do not significantly contribute to steady-state epidermal homeostasis and are not required or responsible for providing keratinocyte stem cells and keratinocyte repopulation following skin injury.