Co-cultures of programmable cells of monocytic origin and mesenchymal stem cells do increase osteogenic differentiation

Abstract

Impaired bone healing can occur with numerous pathologic conditions like trauma, osteoporosis, and infection. Therefore tissue-engineering strategies that aim to enhance osteogenic differentiation of stem cells in order to accelerate bone healing are a major goal of contemporary regenerative research. In this study we cultivated mesenchymal stem cells (MSC) together with the recently patented programmable cells of monocytic origin (PCMO) to test whether co-cultures promote an osteogenic differentiation process. PCMO have recently been shown to have pluripotent characteristics and do support the regeneration processes of liver and heart diseases. Quantitative real time PCR expression profiles of osteogenic marker genes such as alkaline phosphatase in co-cultures of PCMO and MSC showed that MSC differentiated into osteoblast-like cells more rapidly as compared to mono-cultures. Alkaline phosphatase expression and enzyme activity levels were highly increased in co-cultures compared to mono-cultures of MSC. Tests for mineralized matrix formation also indicated that PCMO have a positive effect on co-cultured MSC under osteogenic culture conditions. However, analysis of collagen 1A did not show enhanced expression. In summary, PCMO obviously have the ability to promote osteogenic differentiation of MSC in vitro while their own pluripotent potential is not sufficient to develop osteoblast-like characteristics themselves. ß

Adaptive Regulation of Osteopontin Production by Dendritic Cells Through the Bidirectional Interaction With Mesenchymal Stromal Cells

“…In this line, lymphocytes were reported to inhibit MSC-driven bone regeneration through the secretion of IFN-γ and TNF-α ( 57 ). Similarly, mononuclear phagocytes were reported to drive osteogenic differentiation ( 58 , 59 ). No evidence of a direct role of DCs in MSCs differentiation is so far available.…”

Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing

“…In consideration of this fact, further studies are necessary to investigate the effect of aging on cocultured aged and young MΦ and cells such as MSCs, to further understand the effects of inflammatory cells on bone formation. Limited studies have been reported on this subject [37–40]. Third, although this study was very labor intensive, the experiment was performed only twice and the cells were pooled together.…”

Osteoclast Formation within a Human Co-Culture System on Bone Material as an In Vitro Model for Bone Remodeling Processes

“…Different co-culture models for MSCs/osteoblasts and osteoclasts are found in literature [12,14,15,17,20]. One system consists of hMSCs and generated osteoblasts cultured on two levels of membrane-like structures from mineralized collagen.…”

“…A set-up in which monocytes/osteoclasts and osteoblasts are cultured simultaneously maintains cell-cell interactions and the exchange of soluble factors that are postulated to be essential for the stimulation of osteoclast differentiation [6]. Some studies evaluated the influence of monocytes on the osteogenic differentiation of MSCs [17][18][19][20]. It could be shown that factors such as bone morphogenetic protein 2 are secreted by monocytes that induce an osteogenic lineage commitment of MSCs [19].…”