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

Abstract

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.

Stem Cells from Human Extracted Deciduous Teeth Expanded in Foetal Bovine and Human Sera Express Different Paracrine Factors After Exposure to Freshly Prepared Human Serum

“…Significantly higher amount of HGF, LIF and PDGF-BB in the FBS-SHED supernatants at 120 hours of incubation was also measured (Figure 4). SDF-1, HGF and PDGF-BB are well-known chemoattractant and their role in the regenerative therapy has been acknowledged by several researchers (Li et al 2017;van de Kamp et al 2017;Ponte et al 2007). Therefore, higher expression of paracrine factors from FBS-SHED could be a sign of disruption in the gradient of the paracrine factors following transplantation of MSCs expanded in FBS supplemented media that might lead to non-specific engraftment of the transplanted cells.…”

Enhanced differentiation of mesenchymal stromal cells by three-dimensional culture and azacitidine

“…Consequently, 2D expansion techniques tend to lead to the deterioration of the progenitor properties of MSCs [3415]. There have been many efforts to overcome these limitations by mimicking the natural cell environment, including the use of growth factors, reduction of oxygen tension, and development of 3D expansion systems [7161718]. Although traditionally expanded MSCs are still regularly used in clinical trials because of the relative ease of preparation, alternative expansion techniques that do not compromise the cells' differentiation properties need to be explored.…”

Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine

“…To circumvent the low isolation yield, biomaterials can be used to promote MSC migration into the injured site. For example, a collagen and silk fibroin scaffold functionalized with hepatocyte growth factor to promote chemoattraction was able to induce MSC migration into the subcutaneous injection site in mice …”