Effect of halofuginone, a collagen alpha1(I) inhibitor, on wound healing in normal and irradiated skin: implication for hematopoietic stem cell transplantation.
It is a major interest in the field of hematopoietic stem cell transplantation to reduce scarring of healing wounds with overdeposition of collagen due to radiation injury or graft-versus-host disease. Halofuginone (HF) inhibits collagen alpha1(I) gene expression and overdeposition of collagen. We examined the effect of HF on the healing of full-depth incision wounds inflicted in normal skin or skin areas compromised by local preirradiation with 18 Gy. Preirradiation significantly decreased the tensile strength of the healing wounds at day 14 (by approximately 60%, p < 0.0001). In contrast, HF treatment did not significantly decrease the strength of wounds inflicted in both normal and preirradiated skin. Histological evaluation revealed that HF induced moderate thinning of the dermis accompanied by elevated thickness of the epidermis and enhanced rejoining of subdermal muscles in the wound area. HF only minimally reduced total collagen deposition in both groups, with minor changes in the level of more matured fibrillar collagen network. Our study demonstrates that HF does not significantly affect wound strength. This encourages the possible use of HF as an antifibrotic agent with minimal complications for post-hematopoietic stem cell transplantation complications including radiation toxicity and graft-versus-host disease.
Nagler
Arnon
A
Division of Hematology, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Ohana
Meir
M
Leiba
Merav
M
Levdansky
Lilia
L
Gorodetsky
Raphael
R
D000818:Animals; D002921:Cicatrix / Q000517:prevention & control*; D024042:Collagen Type I / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D018380:Hematopoietic Stem Cell Transplantation; D051379:Mice; D008809:Mice, Inbred C3H; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D052999:Quinazolinones / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D013047:Specific Pathogen-Free Organisms; D013718:Tensile Strength; D019172:Transplantation Conditioning / Q000009:adverse effects; D014945:Wound Healing / Q000187:drug effects* / Q000528:radiation effects; D014950:Wounds, Penetrating / Q000188:drug therapy* / Q000503:physiopathology
D024042:Collagen Type I; D010880:Piperidines; D052999:Quinazolinones; C010176:halofuginone