Fibroblast growth factors as tissue repair and regeneration therapeutics

Abstract

Cell communication is central to the integration of cell function required for the development and homeostasis of multicellular animals. Proteins are an important currency of cell communication, acting locally (auto-, juxta-, or paracrine) or systemically (endocrine). The fibroblast growth factor (FGF) family contributes to the regulation of virtually all aspects of development and organogenesis, and after birth to tissue maintenance, as well as particular aspects of organism physiology. In the West oncology has been the focus of translation of FGF research, whereas in China and to an extent Japan a major focus has been to use FGFs in repair and regeneration settings. These differences have their roots in research history and aims. The Chinese drive into biotechnology and the delivery of engineered clinical grade FGFs by a major Chinese research group were important enablers in this respect. The Chinese language clinical literature is not widely accessible. To put this into context, we provide the essential molecular and functional background to the FGF communication system covering FGF ligands, the heparan sulfate and Klotho co-receptors and FGF receptor (FGFR) tyrosine kinases. We then summarise a selection of case reports that demonstrate the efficacy of engineered recombinant FGF ligands in treating a wide range of conditions that require tissue repair / regeneration. Alongside the functional reasons why application of exogenous FGF ligands does not lead to cancers are described. Together, this highlights that the FGF ligands represent a major opportunity for clinical translation, that has been largely overlooked in the West.

Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling

“…From the clinical translational point of view, FGF2 has been successfully used as a repair/regeneration factor in a variety of conditions such as burns, chronic wounds, oral ulcers, vascular ulcers, diabetic ulcers, pressure ulcers and surgical incisions. To date all of these indications have been limited to topical application . However, a number of recent studies including those from our group have reported the protective effect of FGF2 against I/R injuries in various disease models; particularly in cardiac infarction .…”

Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation

“…Fibroblast growth factors (FGF) regulate embryonic development and homeostasis, including the repair of tissues and organs and specific aspects of metabolism . The basic FGF and acidic FGF, now known as FGF2 and FGF1, respectively, are the most studied FGFs and have been developed as therapeutics . Along with the other paracrine FGFs, they bind to heparan sulfate (HS) chains and interact with FGF receptors (FGFR) (Fig.…”

“…Consequently, FGF1 and FGF2 have been developed as therapeutics for tissue repair. For example, FGF1 and FGF2 are used to accelerate wound healing in skin . FGF1 and FGF2 (natural or Escherichia coli ‐derived) have potent activities on many cell types, but their activity, especially that of FGF1, reduces over time, even at body temperature .…”

Long noncoding RNA LINC01615 promotes keloid development via sponging miR-590-3p to regulate FGF2 expression

“…FGF2 is a well-studied cytokine, which plays a vital role in fibrotic response [31]. FGF2 was reported as an antifibrotic that restrained myofibroblast activation [32,33].…”