2018
DOI: 10.1038/s41536-018-0060-5
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The impact of immune response on endochondral bone regeneration

Abstract: Tissue engineered cartilage substitutes, which induce the process of endochondral ossification, represent a regenerative strategy for bone defect healing. Such constructs typically consist of multipotent mesenchymal stromal cells (MSCs) forming a cartilage template in vitro, which can be implanted to stimulate bone formation in vivo. The use of MSCs of allogeneic origin could potentially improve the clinical utility of the tissue engineered cartilage constructs in three ways. First, ready-to-use construct avai… Show more

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Cited by 46 publications
(33 citation statements)
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References 140 publications
(272 reference statements)
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“…Even though the acute inflammatory response plays an important role in the initiation of the fracture healing cascade, after a few days the initial haematoma is cleared and replaced by a granulation tissue rich in proliferating MSCs [ 148 , 149 ]. In this proliferative phase, the macrophages switch their phenotype to M2 macrophages and start to produce anti-inflammatory mediators involved in tissue regeneration [ 150 ]. Therefore, an adequate inflammatory response represents a necessary phase for the bone repair process [ 151 , 152 ].…”
Section: Discussionmentioning
confidence: 99%
“…Even though the acute inflammatory response plays an important role in the initiation of the fracture healing cascade, after a few days the initial haematoma is cleared and replaced by a granulation tissue rich in proliferating MSCs [ 148 , 149 ]. In this proliferative phase, the macrophages switch their phenotype to M2 macrophages and start to produce anti-inflammatory mediators involved in tissue regeneration [ 150 ]. Therefore, an adequate inflammatory response represents a necessary phase for the bone repair process [ 151 , 152 ].…”
Section: Discussionmentioning
confidence: 99%
“…It is evident that the use of allogeneic or xenogeneic cells represents a clinically and economically attractive option. However, the immunogenicity of non-autologous grafts poses a potential obstacle to the clinical implementation, as it could affect the integration and functionality of the grafted tissues (Longoni et al, 2018 ). Nevertheless, differently from other types of transplantation (e.g., heart, lungs, or liver), in which the grafted organ represents the final functional tissue; in EBR, the cartilage template produced in vitro solely serves as a transient substrate that is remodeled into new, mostly recipient-derived bone tissue (Farrell et al, 2011 ; Scotti et al, 2013 ).…”
Section: Introductionmentioning
confidence: 99%
“…[ 25 ] Compared to D/M and M, the increased number of F4/80+ monocytes/macrophages in the BD/M scaffolds confirmed macrophages’ indispensable role in ectopic bone formation, as previously reported. [ 16,26,27 ] Furthermore, our results indicated that the Dex‐loaded groups could effectively suppress excessive macrophage infiltration (Figure 3B,C; Figure S5A, the Supporting Information) and decreased the M1 (pro‐inflammation) population in the first stage. At first sight, M1 macrophages dominated initially and M2 macrophages increased in all groups (Figure S5C,D, the Supporting Information).…”
Section: Discussionmentioning
confidence: 83%