Abstract
The synergistic crosstalk between osteodifferentiating stem cells and endothelial cells (ECs) gained the deserved consideration, shedding light on the role of angiogenesis for bone formation and healing. A deep understanding of the molecular basis underlying the mutual influence of mesenchymal stem cells (MSCs) and ECs in the osteogenic process may help improve greatly bone regeneration. Here, the authors demonstrated that osteodifferentiating MSCs co-cultured with ECs promote angiogenesis and ECs recruitment. Moreover, through the use of 3D co-culture systems, we showed that ECs are in turn able to further stimulate the osteodifferentiation of MSCs, thus enhancing bone production. These findings highlighted the existence of a virtuous loop between MSCs and ECs that is central to the osteogenic process. Unraveling the molecular mechanisms governing the functional interaction MSCs and ECs holds great potential in the field of regenerative medicine.
Highlights
Bone formation and remodeling require different cell populations to cooperate so as to regenerate a complex 3D tissue under the guidance of chemical and mechanical cues (Genova et al, 2016)
After 7 days of osteodifferentiation, the level of Alkaline phosphatase (ALP) activity was significantly increased compared to undifferentiated adipose-derived stem cells (ASCs) (Figure 1J)
Endothelial cell recruitment and organization becomes paramount to all these processes (Carano and Filvaroff, 2003; Jain, 2003; Hankenson et al, 2011)
Summary
Bone formation and remodeling require different cell populations to cooperate so as to regenerate a complex 3D tissue under the guidance of chemical and mechanical cues (Genova et al, 2016). Angiogenesis, the formation of new blood vessels from existing ones, is essential for bone formation and remodeling. The progressive substitution of an avascular cartilage template by a highly vascularized bone tissue is the characterizing feature of endochondral ossification. Likewise, during the fracture healing, which was classically thought to recapitulate the ontogenesis of the tissue (Urist, 1997), angiogenesis precedes osteogenesis and determines its efficiency. Achieving the desired synergistic crosstalk between osteoblast precursors and endothelial cells is crucial for implementing bone tissue engineered therapies based on the mutual influence of osteogenic and angiogenic cues
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