The usefulness of basic fibroblast growth factor for radiation‐exposed tissue

Abstract

A high dose of ionizing external radiation damage to the skin and soft tissue results in changes in function as well as in the general body condition. Once radiation surpasses the tissue safety or survival level, progressive alteration in the damaged tissue results in tissue loss and then flap loss. Local expression and action of stem cells or local growth factors in the irradiated tissue is mitigated, and external administration is sought to investigate the possibility of skin and soft tissue survival after an elevating flap. Basic fibroblast growth factor (bFGF) is primarily considered as a potent angiogenic growth factor. In burns, resurfacing with a dermal component is required, and bFGF stimulates wound healing and enhances human skin-derived mesenchymal stem cells under serum-free conditions in a dose-dependent manner. Thirty-five male, 4- to 8-week-old CLAWN miniature pigs received radiation exposure to assess the effectiveness of bFGF in terms of the progressive clinical course relevant to human skin and soft tissue. At 2 weeks following 10-Gy irradiation, tissue was preserved in the group receiving subcutaneous placement of a round-type tissue expander and bFGF. The expander plus bFGF group demonstrated significantly greater dermo-epidermal proliferation than the radiation alone, radiation plus bFGF, or expander plus radiation plus vehicle-solution groups, and new blood vessel formation was significantly increased in the expander tissue with bFGF after irradiation (p < 0.01). Electron microscopy revealed that tissue with expander and bFGF maintained more stable skin adnexae with preserved intact epidermis and dermis. Thus, bFGF improved and maintained the tissue viability after immediate irradiation in the skin and soft tissue.

Treatment of Radiation Injury

“…54 In a mini-pig receiving 10-Gy external X-ray radiation to the skin and subcutaneous tissue with a tissue expander underneath the subcutaneous tissue, immediate use of bFGF after radiation successfully protected the tissue from subsequent damage by increasing epithelial proliferation, suppressing the induction of apoptotic cells, and enhancing angiogenic cells. 55 Radiation fibrosis is considered late radiation damage, and TGFb1 plays a pivotal role in the establishment of radiation fibrosis. For the purpose of neutralizing TGF-b antibodies to prevent lung fibrosis in rats 56 or using a small molecule to inhibit TGFb signaling, halofuginone was tested in mice.…”

The Effect of Control-released Basic Fibroblast Growth Factor in Wound Healing

“…7–10 As human recombinant bFGF has been commercially available in Japan, topical administration of bFGF has shown to be effective for various wound healing including burn and radiation ulcer. 11,12 However, daily spray application is necessary because the half-life of bFGF in free form is known to be less than 1 hour 30 and bFGF is easily eliminated from the applied site by diffusion as it is water soluble. Such daily procedure may be time-consuming, may result in patient discomfort, and may increase the potential risk of infection.…”

“…7–10 As human recombinant bFGF has been commercially available in Japan, topical administration of bFGF has shown to be effective for wound healing in clinical situations. 11,12 However, daily administration of bFGF is required for wound healing due to its short half-life in vivo, which occasionally is time-consuming and painful and/or results in discomfort for patients and a potential risk of infection.…”

A Basic Fibroblast Growth Factor Analog for Protection and Mitigation against Acute Radiation Syndromes

“…Over the past two decades, the radiobiological effects of FGFs, including FGF-1, FGF-2, FGF-7 (KGF-1), and FGF-10 (KGF2), have been studied. They have proven to be broad-spectrum agents that mitigate or protect against gastrointestinal, renal, and pulmonary syndromes and lead to improved juvenile bone growth in mice after irradiation (Fuks et al 1994;Okunieff et al 1995Okunieff et al , 1996Neta and Okunieff 1996;Ding et al 1997a and b;Leunig et al 1997;Wang et al 1998;Okunieff et al 2001;Motomura et al 2008;Springer et al 2008;Nakayama et al 2010;Zhang et al 2010;Kinoshita et al 2012).…”