Abstract
Bone regeneration is a complex and well-coordinated process that involves crosstalk between immune cells and resident cells in the injury site. Transplantation of mesenchymal stem cells (MSCs) is a promising strategy to enhance bone regeneration. Growing evidence suggests that macrophages have a significant impact on osteogenesis during bone regeneration. However, the precise mechanisms by which macrophage subtypes influence bone regeneration and how MSCs communicate with macrophages have not yet been fully elucidated. In this systematic literature review, we gathered evidence regarding the crosstalk between MSCs and macrophages during bone regeneration. According to the PRISMA protocol, we extracted literature from PubMed and Embase databases by using “mesenchymal stem cells” and “macrophages” and “bone regeneration” as keywords. Thirty-three studies were selected for this review. MSCs isolated from both bone marrow and adipose tissue and both primary macrophages and macrophage cell lines were used in the selected studies. In conclusion, anti-inflammatory macrophages (M2) have significantly more potential to strengthen bone regeneration compared with naïve (M0) and classically activated macrophages (M1). Transplantation of MSCs induced M1-to-M2 transition and transformed the skeletal microenvironment to facilitate bone regeneration in bone fracture and bone defect models. This review highlights the complexity between MSCs and macrophages, providing more insight into the polarized macrophage behavior in this evolving field of osteoimmunology. The results may serve as a useful reference for definite success in MSC-based therapy based on the critical interaction with macrophages.
Highlights
While we look at the effect of mesenchymal stem cells (MSCs) secretions on macrophages, we further consider the effects of MSCs and macrophages on bone regeneration
The demand for realizing the interaction between MSCs and other cells has soared since transplantation of MSCs is considered a beneficial therapeutic strategy in regenerative medicine
As bone metabolism is tightly regulated by the immune system, macrophages have been drawing attention for their immunomodulatory and osteogenic potential in fracture healing
Summary
Over 20 million people suffer from fractures annually, predominantly due to the prevalence of osteoporosis, osteosarcoma, osteomalacia, osteomyelitis, and atrophic nonunion. One-quarter of these patients have received orthopedic interventions, of which more than half were treatments like bone grafting, which target the afflicted sites [1, 2]. The high recurrence imposes a severe economic burden on the healthcare system. To address this health problem, numerous researchers have investigated the bone regeneration process and intervention in hopes of finding more effective ways to treat these injuries
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