Effect of Halofuginone, a Collagen α1(I) Inhibitor, on Wound Healing in Normal and Irradiated Skin: Implication for Hematopoietic Stem Cell Transplantation

Abstract

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 α1(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 ∼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.

Effects of glutamine on wound healing

“…Increase in the collagen amount in the wound area affects wound healing positively if there is no factor preventing the regular sequence of collagen fibres (11,12). Hydroxyproline (OHP) is an amino acid found in significant amounts in collagen structure and is used for determining the collagen of the tissue (8).…”

An Experimental Model of Urethral Stricture in Rabbits Using Holmium Laser under Urethroscopic Direct Visualization

“…Increased urine penetration leads to greater stricture formation. The inflammatory reaction caused by thermal injury could also promote scar formation [9,12]. Our histological analysis showed massive inflammatory cell infiltrate in the urethral stricture tissue.…”

“…The reported success rate of urethral stricture modeling is approximately 50% [7,9], with half of animals not forming significant strictures after modeling. Model failures may relate to the abundant blood supply of the corpus spongiosum [19].…”

“…Rabbit and dog models of urethral stricture have recently been produced by open surgery, electroresection using a pediatric resectoscope, electrocoagulation with or without endoscopy, and bombing using a special instrument [7,8,9,10,11,12]. In twelve male minipigs stricture formation was established by ligation, urethrotomy or thermocoagulation [13].…”

Análise dos efeitos antiangiogênicos e antiproliferativos da halofuginona na leucemia promielocítica aguda

“…Elkin e colaboradores também demonstraram em modelo de angiogênese em implante na córnea de camundongos, que a angiogênese induzida por bFGF foi reduzida em animais tratados com HF (ELKIN et al, 2000). Por outro lado, em modelo de cicatrização após irradiação, a HF também não foi capaz de inibir a formação de novos vasos no tecido epitelial (NAGLER et al, 2007). Esses resultados podem sugerir, que a influência do tratamento com HF sobre a neovasculogênese pode ser variável em diferentes tecidos.…”