Hepatocyte Growth Factor-Loaded Biomaterials for Mesenchymal Stem Cell Recruitment

Abstract

Human adult mesenchymal stem cells (MSC) can be readily harvested from bone marrow through aspiration. MSC are involved in tissue regeneration and repair, particularly in wound healing. Due to their high self-renewal capacity and excellent differentiation potential in vitro, MSC are ideally suited for regenerative medicine. The complex interactions of MSC with their environment and their influence on the molecular and functional levels are widely studied but not completely understood. MSC secrete, for example, hepatocyte growth factor (HGF), whose concentration is enhanced in wounded areas and which is shown to act as a chemoattractant for MSC. We produced HGF-loaded biomaterials based on collagen and fibrin gels to develop a recruitment system for endogenous MSC to improve wound healing. Here, we report that HGF incorporated into collagen or fibrin gels leads to enhanced and directed MSC migration in vitro. HGF-loaded biomaterials might be potentially used as in vivo wound dressings to recruit endogenous MSC from tissue-specific niches towards the wounded area. This novel approach may help to reduce costly multistep procedures of cell isolation, in vitro culture, and transplantation usually used in tissue engineering.

Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy?

“…Another growth factor involved in MSC migration is hepatocyte growth factor (HGF), which binds to c-met [63,68,80] . Both PDGF-BB and HGF have been loaded on gels or scaffolds as a means to improve the in vitro migration of MSCs [92,93] .…”

Transplantation of MSCs Overexpressing HGF into a Rat Model of Liver Fibrosis

“…Several studies [11][12][13] have reported that HGF induced MSCs to differentiate into hepatocytes in vitro and promotes MSCs in the liver in vivo. Therefore, MSCs combined with HGF gene modification may be a better strategy for the treatment of liver fibrosis.…”

Enhanced expression of hepatocyte growth factor in the healing of experimental acute tympanic membrane perforation

“…Then a longer release from fibroblasts takes place [22]. HGF is a potent chemoattractant for mesenchymal stem cells [23] and has been also shown to be a powerful regulator of proteolytic enzymes involved in extracellular matrix remodeling [22]. A study on skin wound healing has provided evidence that HGF can accelerate reepithelialization by transforming epidermal cells through dedifferentiation to stemlike cells, with powerful ability of proliferation and migration [24].…”