Mesenchymal stem cells can be recruited to wounded tissue via hepatocyte growth factor-loaded biomaterials

J Tissue Eng Regen Med. 2017 Nov;11(11):2988-2998. doi: 10.1002/term.2201. Epub 2016 Sep 19.


Mesenchymal stem cells (MSC) are precursor cells of mesodermal tissue and, because of their trophic phenotype, they are known to play beneficial roles in wound healing. In addition, various tissue engineering strategies are based on MSC/biomaterial constructs. As the isolation and expansion of MSCs is a long-term process, a major goal is to develop an endogenous stem cell recruitment system that circumvents all ex vivo steps generally used for tissue engineering. Therefore collagen and silk fibroin were loaded with hepatocyte growth factor (HGF), a chemoattractant for MSCs. Collagen was mixed with HGF during polymerization, while silk fibroin and HGF were produced as fusion proteins by transgenic silkworms. To demonstrate release of active HGF, enzyme-linked immunosorbent assay, in vitro migration assays and animal studies were performed to demonstrate MSC migration in vivo, followed by detailed examinations of the immunological effects of the biomaterials. Hepatocyte growth factor was released burst-like, both from silk fibroin and collagen during the first 8 h and gradually for up to 168 h in vitro. Directed migration in vitro was demonstrated when MSCs were exposed to HGF. In vivo, HGF-loaded collagen and silk fibroin were tolerated as subcutaneous implants. In addition, it was proved that endogenous MSCs were recruited from the local environment. These results show for the first time recruitment of endogenous MSCs to HGF-loaded collagen (fast degradable) and silk fibroin scaffolds (long-term degradable) in vitro and in vivo. This knowledge could be applied to make off-the-shelf, readily available constructs for use in patients with chronic wound or burns. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: cell migration; hepatocyte growth factor; mesenchymal stem cells; recruitment; silk fibroin; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials* / chemistry
  • Biocompatible Materials* / pharmacokinetics
  • Biocompatible Materials* / pharmacology
  • Cell Movement / drug effects*
  • Drug Implants / chemistry
  • Drug Implants / pharmacokinetics
  • Drug Implants / pharmacology
  • Female
  • Fibroins / chemistry
  • Fibroins / pharmacokinetics
  • Fibroins / pharmacology
  • Hepatocyte Growth Factor* / chemistry
  • Hepatocyte Growth Factor* / pharmacokinetics
  • Hepatocyte Growth Factor* / pharmacology
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology
  • Wounds and Injuries / therapy*


  • Biocompatible Materials
  • Drug Implants
  • Hepatocyte Growth Factor
  • Fibroins