Comparison of the Therapeutic Effects Recombinant Human Acidic and Basic Fibroblast Growth Factors in Wound Healing in Diabetic Patients

Abstract

To explore an optimal improvement of diabetic wound healing we have comparatively studied the effects of recombinant human acidic and basic fibroblast growth factors (rhaFGF and rhbFGF) on the healing impaired skin wounds in diabetic patients. Before using rhaFGF in diabetic patients, its pharmacokinetic features and possible toxic effects were evaluated using a rabbit model. For the 139 diabetic patients, 25% of them were divided into the group to receive topical rhbFGF daily at the dose of 100 U/0.1 ml/cm 2 as positive control (n = 35), and the remainder to receive topical rhaFGF at the same dose as rhbFGF (n = 104). Pharmacokinetic studies showed that plasma concentration of rhaFGF rapidly increased and reached to peak levels at 0.5 hr and then quickly decreased to normal levels at 3 hr after topical application on the wounds. No detectable toxic effects were found by examining multiple organs of the rabbits at 28 days after applying rhaFGF at 900 U/cm 2 . Topical application of either rhbFGF or rhaFGF at 100 U/cm 2 effectively cured the skin wounds in the diabetic patients. Although there was no remarkable difference between groups, rhaFGF provided a slightly better healing rate and efficiency than rhbFGF did. Therefore rhaFGF will become an alternative candidate for diabetic wounds, especially when diabetic wounds were in acidic environment due to bacterial infection.

Cardiac Protection by Basic Fibroblast Growth Factor from Ischemia/Reperfusion-Induced Injury in Diabetic Rats

“…22) Supplementation of exogenous FGFs attenuated diabetes-caused neuronal and gastric tissue damage. 23,24) We have performed experimental and clinical studies, demonstrating that topical application of recombinant human acidic FGF (rhaFGF) and basic FGF (rhbFGF) promoted the healing of skin ulcer in diabetic patients, 25) and diabetic rats. 26) Cardiac infarction and dysfunction are life-threatening diseases.…”

Combined Use of Acid Fibroblast Growth Factor, Granulocyte Colony-stimulating Factor and Zinc Sulphate Accelerates Diabetic Ulcer Healing

“…We did not include non-diabetic group in this study since each of the approach used in the combination has been used extensively to non-diabetic animals. 19,33,[39][40][41] In these previous studies, application of the exogenous growth factors or Zn did not always stimulate the wound healing process, for which one of the reasons is because normal tissue is not defect for these growth factors or nutrients such as Zn. 42) Diabetic induction by STZ and the full-thickness skin wound for the diabetic rats was made as described in the pilot study.…”

“…19) For this end, diabetic and age-matched nondiabetic (control) rats were anesthetized with 5% Chloral Hydrate (0.5 ml/kg body weight) and depilated using 8% sodium sulfide. A round marker (diameter 2.4 cm, 4.52 cm 2 ) was made on the back of rats with methylrosanilinium chloride.…”

“…18) However, only application of a single growth factor remains unable to obtain the maximal therapeutic purpose. 19) These studies suggest multiple mechanisms contributing to diabetes-impaired wound healing.…”

Expression of The Human Acidic Fibroblast Growth Factor in Transgenic Tomato and Safety Assessment of Transgenic Lines

“…When kanamycin selection was applied, authors reported similar TEs: 9% (8), 9.9% (33). However, in publications where the main purpose is development of transgenic tomato plants producing valuable recombinant proteins, the TE was not mentioned (26,53,61).…”