TY - JOUR
T1 - Pharmacological mobilization of endogenous stem cells significantly promotes skin regeneration after full-thickness excision
T2 - The synergistic activity of AMD3100 and tacrolimus
AU - Lin, Qing
AU - Wesson, Russell N.
AU - Maeda, Hiromichi
AU - Wang, Yongchun
AU - Cui, Zhu
AU - Liu, Jun O.
AU - Cameron, Andrew M.
AU - Gao, Bin
AU - Montgomery, Robert A.
AU - Williams, George M.
AU - Sun, Zhaoli
PY - 2014/9
Y1 - 2014/9
N2 - Stem cell therapy has shown promise in treating a variety of pathologies including skin wounds, but practical applications remain elusive. Here, we demonstrate that endogenous stem cell mobilization produced by AMD3100 and low-dose tacrolimus is able to reduce by 25% the time of complete healing of full-thickness wounds created by surgical excision. Equally important, healing was accompanied by reduced scar formation and regeneration of hair follicles. Searching for mechanisms, we found that AMD3100 combined with low-dose tacrolimus mobilized increased number of lineage-negative c-Kit+, CD34+, and CD133+ stem cells. Low-dose tacrolimus also increased the number of SDF-1-bearing macrophages in the wound sites amplifying the "pull" of mobilized stem cells into the wound. Lineage tracing demonstrated the critical role of CD133 stem cells in enhanced capillary and hair follicle neogenesis, contributing to more rapid and perfect healing. Our findings offer a significant therapeutic approach to wound healing and tissue regeneration.
AB - Stem cell therapy has shown promise in treating a variety of pathologies including skin wounds, but practical applications remain elusive. Here, we demonstrate that endogenous stem cell mobilization produced by AMD3100 and low-dose tacrolimus is able to reduce by 25% the time of complete healing of full-thickness wounds created by surgical excision. Equally important, healing was accompanied by reduced scar formation and regeneration of hair follicles. Searching for mechanisms, we found that AMD3100 combined with low-dose tacrolimus mobilized increased number of lineage-negative c-Kit+, CD34+, and CD133+ stem cells. Low-dose tacrolimus also increased the number of SDF-1-bearing macrophages in the wound sites amplifying the "pull" of mobilized stem cells into the wound. Lineage tracing demonstrated the critical role of CD133 stem cells in enhanced capillary and hair follicle neogenesis, contributing to more rapid and perfect healing. Our findings offer a significant therapeutic approach to wound healing and tissue regeneration.
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U2 - 10.1038/jid.2014.162
DO - 10.1038/jid.2014.162
M3 - Article
C2 - 24682043
AN - SCOPUS:84906327298
SN - 0022-202X
VL - 134
SP - 2458
EP - 2468
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 9
ER -