Expansion of Murine Periosteal Progenitor Cells with Fibroblast Growth Factor 2 Reveals an Intrinsic Endochondral Ossification Program Mediated by Bone Morphogenetic Protein 2

Abstract

The preservation of the bone-forming potential of skeletal progenitor cells during their ex vivo expansion remains one of the major challenges for cell-based bone regeneration strategies. We report that expansion of murine periosteal cells in the presence of FGF2, a signal present during the early stages of fracture healing, is necessary and sufficient to maintain their ability to organize in vivo into a cartilage template which gives rise to mature bone. Implantation of FGF2-primed cells in a large bone defect in mice resulted in complete healing, demonstrating the feasibility of using this approach for bone tissue engineering purposes. Mechanistically, the enhanced endochondral ossification potential of FGF2-expanded periosteal cells is predominantly driven by an increased production of BMP2 and is additionally linked to an improved preservation of skeletal progenitor cells in the cultures. This characteristic is unique for periosteal cells, as FGF2-primed bone marrow stromal cells formed significantly less bone and progressed exclusively through the intramembranous pathway, revealing essential differences between both cell pools. Taken together, our findings provide insight in the molecular regulation of fracture repair by identifying a unique interaction between periosteal cells and FGF2. These insights may promote the development of cell-based therapeutic strategies for bone regeneration which are independent of the in vivo use of growth factors, thus limiting undesired side effects.

The Use of Adipose Tissue-Derived Progenitors in Bone Tissue Engineering - a Review

“…However, it is probable that when used in reduced dose in combination with small chemical molecules (like NMP) it may stimulate the bone forming potential of the implanted cells, but the clinical evidence is lacking. Alternatively, the use of growth factors can be restricted to the pre-implantation cell expansion phase in order to enhance the regenerative potency of the implanted MSCs and thereby prevent possible side effects caused by in vivo application of growth factors [63]. …”

A bio-artificial poly([D,L]-lactide-co-glycolide) drug-eluting nanofibrous periosteum for segmental long bone open fractures with significant periosteal stripping injuries

“…An initial damage-control operation is recommended to remove all contaminating materials and to provide temporary bone stabilization. 2,16 All devitalized skin, muscle, periosteum, and sequestrated bone tissue should be excised during debridement procedures to gain sufficient control of …”

“…2 Often, the damaged periosteum cannot be repaired directly during treatment because of the significant stripping injuries and tissue losses that occur in association with open fractures. 3 The management of severe open fractures poses several challenges for surgeons because open fractures are associated with numerous problems, including infections, tissue defects, and nonunions.…”

Serum of patients with active rheumatoid arthritis inhibits differentiation of osteochondrogenic precursor cells

“…We found that RA-sera did inhibit matrix mineralization in ATDC5 but not in HPDC micromasses. This difference might be explained by differences in the cell populations we used, that is, the ATDC5 murine cell line represents a homogeneous cell population, while the periost-derived cells represent a more heterogeneous population, containing fibroblasts, skeletal progenitors, and endothelial progenitors (40,41). This difference might also be the result of differences in the degree of inflammation of the patients from whom the active RA-sera were obtained.…”