Tissue regeneration using macrophage migration inhibitory factor-impregnated gelatin microbeads in cutaneous wounds.
Migration inhibitory factor (MIF) responds to tissue damage and regulates inflammatory and immunological processes. To elucidate the function of MIF in cutaneous wound healing, we analyzed MIF knockout (KO) mice. After the excision of wounds from the dorsal skin of MIF KO and wild-type (WT) mice, healing was significantly delayed in MIF KO mice compared to WT mice. Lipopolysaccharide treatment significantly increased [(3)H]thymidine uptake in WT mouse fibroblasts compared to MIF KO mouse fibroblasts. Furthermore, there was a significant reduction in fibroblast and keratinocyte migration observed in MIF KO mice after 1-oleoyl-2-lysophosphatidic acid treatment. We subsequently examined whether MIF-impregnated gelatin slow-release microbeads could accelerate skin wound healing. Injection of more than 1.5 microg/500 microl of MIF-impregnated gelatin microbeads around a wound edge accelerated wound healing compared to a single MIF injection without the use of microbeads. MIF-impregnated gelatin microbeads also accelerated skin wound healing in C57BL/6 mice and diabetic db/db mice. Furthermore, incorporating MIF-impregnated gelatin microbeads into an artificial dermis implanted into MIF KO mice accelerated procollagen production and capillary formation. These findings suggest that MIF is crucial in accelerating cutaneous wound healing and that MIF-impregnated gelatin microbeads represent a promising treatment to facilitate skin wound healing.
Zhao
Yunan
Y
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Shimizu
Tadamichi
T
Nishihira
Jun
J
Koyama
Yoshikazu
Y
Kushibiki
Toshihiro
T
Honda
Ayumi
A
Watanabe
Hirokazu
H
Abe
Riichiro
R
Tabata
Yasuhiko
Y
Shimizu
Hiroshi
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D002465:Cell Movement / Q000187:drug effects; D017931:DNA Primers; D004261:DNA Replication / Q000187:drug effects; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005780:Gelatin; D048091:Guided Tissue Regeneration / Q000379:methods*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000293:injuries*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D017931:DNA Primers; D020690:GTPase-Activating Proteins; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; C085379:rho GTPase-activating protein; D005780:Gelatin