Platelet-Derived Growth Factor Stimulated Migration of Bone Marrow Mesenchymal Stem Cells into an Injectable Gelatin-Hydroxyphenyl Propionic Acid Matrix

Abstract

Bone marrow mesenchymal stem cells (bMSCs) are responsible in the repair of injured tissue through differentiation into multiple cell types and secretion of paracrine factors, and thus have a broad application profile in tissue engineering/regenerative medicine, especially for the musculoskeletal system. The lesion due to injury or disease may be a closed irregular-shaped cavity deep within tissue necessitating an injectable biomaterial permissive of host (endogenous) cell migration, proliferation and differentiation. Gelatin-hydroxyphenyl propionic acid (Gtn-HPA) is a natural biopolymer hydrogel which is covalently cross-linked by horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) in situ and can be delivered to the lesion by needle injection. Growth factors and cytokines can be directly incorporated into the gel or into nano- and micro-particles, which can be employed for sustained release of biomolecules while maintaining their bioactivity. In this study, we selected polyelectrolyte complex nanoparticles (PCNs) prepared with dextran sulfate and chitosan as the carrier for platelet-derived growth factor (PDGF)-BB and stromal cell-derived factor (SDF)-1α, which have been tested effectively in recruiting stem cells. Our in vitro results showed a high degree of viability of bMSCs through the process of Gtn-HPA covalent cross-linking gelation. The Gtn-HPA matrix was highly permissive of bMSC migration, proliferation, and differentiation. PDGF-BB (20 ng/mL) directly incorporated into the gel and, alternatively, released from PCNs stimulated bMSC migration and proliferation. There were only small differences in the results for the direct incorporation of PDGF into the gel compared with its release from PCNs, and for increased doses of the growth factor (200 ng/mL and 2 µg/mL). In contrast, SDF-1α elicited an increase in migration and proliferation only when released from PCNs; its effect on migration was notably less than PDGF-BB. The in vitro results demonstrate that PDGF-BB substantially increases migration of bMSCs into Gtn-HPA and their proliferation in the gel, and that these benefits can be derived from incorporation of a relatively low dose of the growth factor directly into the gel. These findings commend the use of Gtn-HPA/PDGF-BB as an injectable therapeutic agent to treat defects in musculoskeletal tissues.

MicroRNA-140-5p was involved in osteonecrosis of the femoral head by inhibiting osteogenic diffentiation and migration of hBMSCs

“…Under normal circumstances, BMSCs in the adult femur is found mainly in the femoral neck. When necessary, BMSCs can migrate to the femoral head region for bone repair and reconstruction 37,38 . In addition, miR-217 has been reported to regulate the migration of BMSCs 39 .…”

Platelet-Rich Plasma Lysate-Incorporating Gelatin Hydrogel as a Scaffold for Bone Reconstruction

“…Only gels containing 1.7 mM H 2 O 2 displayed a slight decrease in cell viability to ~93% [ 30 ]. In a recent study employing caprine bone-marrow-derived MSCs, 99% of the cells exposed to the Gtn–HPA cross-linking process using 1.2 mM H 2 O 2 were found to remain viable using a live/dead cell assay [ 31 ].…”

“…For imaging, the same confocal microscopy mentioned above was used using the 10× macro-objective lens. This method has been tested previously by our lab and published by Niu et al, 2021 [ 31 ].…”

Intervertebral Disc Degeneration: Biomaterials and Tissue Engineering Strategies toward Precision Medicine

“…Recent advancement of biomaterials as a delivery system has provided a broad range of benefits in tissue engineering and regenerative medicine. [78] Biomaterials can transport exogenous therapeutic molecules, including growth factors (PDGF, FGF, IGF-I, and TGF-𝛽1), [79,80,81,82] cellular regulator, drug or inhibitor (anti-TNF𝛼, IL-1ra, celecoxib, rapamycin, NF-𝜅B decoy) [83,84,85,86] from the cargo to the target site specifically to regulate cellular signaling, thereby dictating cellular responses, including anticatabolic, antioxidative, antiapoptotic, anti-inflammatory, and anabolic effects for IVD regeneration. [87] This delivery system provides sustained release of the therapeutic molecules over time for a longterm efficacy.…”