title: Pharmacological mobilization of endogenous stem cells significantly promotes skin regeneration after full-thickness excision: the synergistic activity of AMD3100 and tacrolimus.
abstract: 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.
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Russell N
authors.initials: RN
authors.lastname: Wesson
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Jun O
authors.initials: JO
authors.lastname: Liu
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Cameron
authors.affiliation: Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Montgomery
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: George M
authors.initials: GM
authors.lastname: Williams
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Electronic address: zsun2@jhmi.edu.
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D001596:Benzylamines; D019070:Cell Lineage / Q000187:drug effects; D002921:Cicatrix / Q000473:pathology; D000080027:Cyclams; D004195:Disease Models, Animal; D004357:Drug Synergism; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011919:Rats, Inbred Strains; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors; D044968:Regenerative Medicine / Q000379:methods; D012867:Skin / Q000166:cytology*; D016559:Tacrolimus / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D007166:Immunosuppressive Agents; D019718:Receptors, CXCR4; C088327:plerixafor; D016559:Tacrolimus