Pharmacological mobilization of endogenous stem cells significantly promotes skin regeneration after full-thickness excision: the synergistic activity of AMD3100 and tacrolimus

J Invest Dermatol. 2014 Sep;134(9):2458-2468. doi: 10.1038/jid.2014.162. Epub 2014 Mar 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzylamines
  • Cell Lineage / drug effects
  • Cicatrix / pathology
  • Cyclams
  • Disease Models, Animal
  • Drug Synergism
  • Hair Follicle / cytology
  • Hair Follicle / drug effects
  • Hematopoietic Stem Cell Mobilization / methods*
  • Heterocyclic Compounds / pharmacology*
  • Immunosuppressive Agents / pharmacology
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Rats, Inbred Strains
  • Receptors, CXCR4 / antagonists & inhibitors
  • Regenerative Medicine / methods
  • Skin / cytology*
  • Tacrolimus / pharmacology*
  • Wound Healing / drug effects


  • Benzylamines
  • Cyclams
  • Heterocyclic Compounds
  • Immunosuppressive Agents
  • Receptors, CXCR4
  • plerixafor
  • Tacrolimus