Palifermin for the protection and regeneration of epithelial tissues following injury: new findings in basic research and pre-clinical models

被引:40
作者
Finch, Paul W.
Cross, Lawrence J. Mark [1 ]
McAuley, Daniel F. [1 ]
Farrell, Catherine L. [2 ]
机构
[1] Queens Univ Belfast, Ctr Infect & Immun, Belfast, Antrim, North Ireland
[2] Epistem Ltd, Novel Therapies Div, Manchester M13 9XX, Lancs, England
关键词
palifermin; KGF; FGFR2b; cytoprotection; epithelial repair; GVHD; immune reconstitution; mucositis; pericardial adhesions; pre-synaptic organizing molecules; pulmonary injury; regeneration; urothelium; wound healing; KERATINOCYTE GROWTH-FACTOR; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; INFLAMMATORY-BOWEL-DISEASE; INDUCED LUNG INJURY; HUMAN BREAST-CANCER; FACTOR RECEPTOR 2; T-CELL RECONSTITUTION; FACTOR MESSENGER-RNA; INHERITED EPIDERMOLYSIS-BULLOSA;
D O I
10.1111/jcmm.12091
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Keratinocyte growth factor (KGF) is a paracrine-acting epithelial mitogen produced by cells of mesenchymal origin, that plays an important role in protecting and repairing epithelial tissues. Pre-clinical data initially demonstrated that a recombinant truncated KGF (palifermin) could reduce gastrointestinal injury and mortality resulting from a variety of toxic exposures. Furthermore, the use of palifermin in patients with hematological malignancies reduced the incidence and duration of severe oral mucositis experienced after intensive chemoradiotherapy. Based upon these findings, as well as the observation that KGF receptors are expressed in many, if not all, epithelial tissues, pre-clinical studies have been conducted to determine the efficacy of palifermin in protecting different epithelial tissues from toxic injury in an attempt to model various clinical situations in which it might prove to be of benefit in limiting tissue damage. In this article, we review these studies to provide the pre-clinical background for clinical trials that are described in the accompanying article and the rationale for additional clinical applications of palifermin.
引用
收藏
页码:1065 / 1087
页数:23
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