Initial immune reaction and angiogenesis in bone healing

Abstract

During hematoma formation following injury, an inflammatory reaction ensues as an initial step in the healing process. As granulation tissue matures, revascularization is a prerequisite for successful healing. The hypothesis of this study was that scarless tissue reconstitution in the regenerative bone healing process is dependent on a balanced immune reaction that initiates revasculatory steps. To test this hypothesis, cellular composition and expression profiles of a bone hematoma (regenerative, scarless) was compared with a muscle soft tissue hematoma (healing with a scar) in a sheep model. Upregulation of regulatory T helper cells and anti-inflammatory cytokine expression (IL-10) coincided with an upregulation of angiogenic factors (HIF1α and HIF1α regulated genes) in the regenerative bone hematoma but not in the soft tissue hematoma. These results indicate that the timely termination of inflammation and early onset of revascularization are interdependent and essential for a regenerative healing process. Prolonged pro-inflammatory signaling occurring in a delayed bone-healing model supports the finding that timely termination of inflammation furthers the regenerative process. Differing cellular compositions are due to different cell sources invading the hematoma, determining the ensuing cytokine expression profile and thus paving the path for regenerative healing in bone or the formation of scar tissue in muscle injury.

Adsorbed fibrinogen leads to improved bone regeneration and correlates with differences in the systemic immune response

“…Immune cells are a source of soluble factors, like cytokines, which have angiogenic effects [62], and recruitment capabilities towards other cells, namely MSC [19]. Nair and colleagues have shown that stem cells, namely MSC, can be recruited after biomaterial implantation in a sub-cutaneous mouse model and that cell recruitment may be inhibited by an anti-inflammatory drug [63].…”

Status of Bone Mineral Density in Children with Type 1 Diabetes Mellitus and Its Related Factors

“…Considering importance of osteoporosis in the individual's activity and increased risk of pathological fractures in the future, determining prevalence and risk factors of the problem in children with type 1 DM and necessary treatments for its reduction is essential (13). Previous studies showed that type 1 DM causes reduction of bone density and ossification markers and increasing bone loss markers, and BMD is a good indicator for detecting changes in bone quality (14)(15)(16)(17)(18)(19)(20).…”

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

“…This type results in graft/ cell rejection. In contrast, in the type II response, the type II T helper lymphocytes trigger macrophage type II activity, which is a remodeling reaction that causes graft/cell acceptance in the body [Schmidt-Bleek et al, 2014;Moshiri et al, 2015a, b]. Recent investigations have shown that allogeneic MSCs promote the polarization of monocytes into an anti-inflammatory M2 phenotype.…”