Sphingosylphosphorylcholine (lysosphingomyelin or SPC) is an effective
and broad spectrum cell growth promoting agent and a candidate for ev
aluation on wound healing. The effect of SPC on full-thickness excisio
n and incision wounds in genetically healing-impaired diabetic (db/db)
mice was evaluated by measurement of wound area, skin strength, and t
issue histology. The effect on cell proliferation was measured in vivo
by incorporation of bromo-deoxyuridine and in vitro by [H-3]thymidine
incorporation. SPC increased the rate of wound closure, with a statis
tically significant improvement in measured wound areas (p < 0.02, com
pared with vehicle controls), The optimum concentration was 2-3 mu M.
SPC, alone and in combination with insulin, stimulated DNA synthesis i
n cells known to participate in wound healing, including microvascular
endothelial cells, In vivo, SPC stimulated proliferation of keratinoc
ytes, fibroblasts, endothelial cells, and cells around sebaceous gland
s and hair follicles at day 2-4 postwound, resulting in a complete re-
epithelialization and profound granulation tissue formation in excisio
nal and incisional wound sites of db/db and db/+ mice. Quantitative as
sessment of wound tissue section morphology indicated that SPC induced
up to a 3-fold increase in the numbers of mitotic cells, resulted in
a smaller cross-sectional scar area, and led to more normalized tissue
in the wound sites, SPC had no deleterious effect on wound skin stren
gth. In conclusion, the acceleration of dermal wound healing in animal
models suggests that SPC could be an interesting candidate for clinic
al application.