Impact of developmental origin, niche mechanics and oxygen availability on osteogenic differentiation capacity of mesenchymal stem/stromal cells

Abstract

Mesenchymal Stem/Stromal Cells (MSCs) have been widely considered as a promising source of cells for tissue regeneration. Among other stem cells, they are characterized by a high osteogenic potential. Intensive studies in this field had shown that even if basic osteogenic differentiation is relatively simple, its clinical application requires more sophisticated approaches to prepare effective and safe cell therapy products. The aim of this review is to underline biological, physical and chemical factors which play a crucial role in osteogenic differentiation of MSCs. Existence of two distinct mechanisms of ossification (intramembranous and endochondral) indicate that choosing a proper source of MSCs may be critical for successful regeneration of a particular bone type. In this context, Dental Pulp Stem Cells representing a group of MSCs and originating from neural crest ( a structure responsible for development of cranial bones) are considered as the most promising for skull bone defect repair. Factors which facilitate osteogenic differentiation of MSCs include changes in forces exerted on cells during development. Thus, culturing of cells in hydrogels or on biocompatible three-dimensional scaffolds improves osteogenic differentiation of MSCs by both, the mechanotransductive and chemical impact on cells. Moreover, atmospheric oxygen concentration routinely used for cell cultures in vitro does not correspond to lower oxygen concentration present in stem cell niches. A decrease in oxygen concentration allows to create more physiological cell culture conditions, mimicking the ones in stem cell niches, which promote the MSCs stemness. Altogether, factors discussed in this review provide exciting opportunities to boost MSCs propagation and osteogenic differentiation which is crucial for successful clinical applications.

Multilineage Differentiation Potential of Human Dental Pulp Stem Cells—Impact of 3D and Hypoxic Environment on Osteogenesis In Vitro

“…The unique features of DPSCs resulted in the first clinical application for the treatment of neurodegenerative diseases [28]. Moreover, DPSCs, when cultured under appropriate conditions, are known to exhibit osteogenic potential [18,29]. While long bones develop from mesoderm during the process of endochondral ossification, flat bones of the skull, similar to the mandible, are formed during the intramembranous ossification from ectomesenchymal cells derived from neural crest SCs [30,31].…”

Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation

“…It also provides a functional milieu for blood production in the BM and progenitor cell niche formation. In this regard, the bone contains both mesenchymal and hematopoietic cell compartments[ 41 - 43 ].…”

“…Healthy bone is a dynamic organ with a constant balance of fine-tuned bone resorption and new tissue generation. It confers bone’s ability to repair itself by continuous skeletal adjustment to mechanical forces in varying environmental conditions[ 41 , 43 ]. Therefore, impairment in cell differentiation can result in different bone pathologies.…”

“…Also, systemic hormones, such as parathyroid hormone, glucocorticoids, estrogens, and local growth factors, such as bone TGF-β1/2, IGF, fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor, prostaglandins, and MAPK signaling molecules, regulate MSC osteogenic differentiation[ 41 ]. Furthermore, MSC osteoblastogenesis can also be induced in vitro by adding a combination of dexamethasone, beta-glycerophosphate, and ascorbic acid to the cell culture medium[ 91 ].…”

The emerging role of mechanical and topographical factors in the development and treatment of nervous system disorders: dark and light sides of the force

“…Cells are known to respond mechanically to anticancer treatment, changing their mechanical properties in a drug-dependent manner [7,8]. Conversely, proper manipulation of the microenvironment's mechanical properties may increase the differentiation capability and regenerative potential of the cells [9][10][11]. Transmission of force into the biological signal is called mechanotransduction and is currently recognized as a new approach in understanding how diseases arise and propagate.…”