BMSC-derived exosomal CD73 mediated macrophage polarization promotes osteoblastic differentiation in diabetes

Stem cell-derived exosomes have exhibited promise for applications in tissue regeneration. However, the osteogenic ability of exosomes derived from bone marrow mesenchymal stem cells(BMSCs) in diabetes is impaired. Exosomes play a role in intercellular communication and affect the functional status of many adjacent cells. The micro-inflammatory state in diabetes often leads to a higher proportion of M1/M2 macrophages in the tissue damage area than in non-diabetic individuals, which is unfavorable for tissue regeneration and delays wound healing. In the present study, we compared the macrophage polarization effect of exosomes secreted by BMSCs derived from type 2 diabetic rats(Exo(dm)) and derived from normal rats(Exo(wis)). The impact of Exo(dm) on regulating the polarization to M2 type in macrophages was weaker than that of Exo(wis), which brought less osteogenesis and was one of the reasons for poor regenerative repair of bone defects. To go a step further, Exo(dm) has lower expression of CD73, which could activate adenosine receptor A2b and cAMP/AKP pathway, leading to disorder of macrophage polarization in diabetes.