Abstract
BackgroundThe inflammation and regeneration process may be accompanied by the shift in the M1/M2 polarization of macrophages to adapt to extracellular signals. How the macrophages responded to the altered immunological environment in the periodontal niche after stem cell transplantation has never been explored. The purpose of present study is to investigate whether M1/M2 polarization of macrophages participated in the tissue homeostasis and wound healing during periodontal ligament stem cell (PDLSC)-based periodontal regeneration.MethodsA rat periodontal defect model was utilized to observe the regeneration process in the PDLSC transplantation-enhanced periodontal repair. Dynamic changes in the markers of M1/M2 macrophages were observed on days 3, 7, and 21 post surgery. In addition, the outcome of regeneration was analyzed on day 21 after surgery. To further investigate the effect of PDLSCs on macrophage polarization, the conditioned medium of PDLSCs was utilized to treat M0, M1, and M2 macrophages for 24 h; markers of M1/M2 polarization were evaluated in macrophages.ResultsElevated bone volume and average thickness of bone trabecular was observed in the PDLSC-treated group by micro-computed tomography on day 21. In addition, enhanced periodontal regeneration was observed in the PDLSC-treated group with cementum-like structure regeneration and collagen fiber formation, which inserted into the newly formed cementum. On day 3, PDLSC transplantation increased IL-10 level in the periodontal tissue, while decreased TNF-α in the early stage of periodontal regeneration. On day 7, enhanced CD163+ cell infiltration and heightened expression of markers of M2 macrophages were observed. Furthermore, conditioned medium from PDLSC culture induced macrophage polarization towards the anti-inflammatory phenotype by downregulating TNF-α and upregulating IL-10, Arg-1, and CD163 in vitro.ConclusionsPDLSCs could induce macrophage polarization towards the M2 phenotype, and the shift in the polarization towards M2 macrophages in the early stage of tissue repair contributed to the enhanced periodontal regeneration after stem cell transplantation. Therefore, signals from the transplanted PDLSCs might alter the immune microenvironment to enhance periodontal regeneration.
Highlights
The inflammation and regeneration process may be accompanied by the shift in the Classic-activated macrophage (M1)/Alternatively activated macrophage (M2) polarization of macrophages to adapt to extracellular signals
Periodontal ligament stem cells (PDLSCs) promoted periodontal regeneration in vivo Allogeneic PDLSCs carried by membrane materials were transplanted into the periodontal defect in rats
The outcome of PDLSCs transplantation was reported by several pre-clinical experiments [25], our study further demonstrated that PDLSCs transplantation might improve periodontal regeneration by its paracrine effect on macrophage polarization
Summary
The inflammation and regeneration process may be accompanied by the shift in the M1/M2 polarization of macrophages to adapt to extracellular signals. The purpose of present study is to investigate whether M1/M2 polarization of macrophages participated in the tissue homeostasis and wound healing during periodontal ligament stem cell (PDLSC)-based periodontal regeneration. Among various mesenchymal stem cells (MSCs) used for periodontal regeneration, PDLSCs were proved to be a reliable source to form new cementum-like structure in vivo [6]. Treatment based on PDLSCs showed promising results in tissue regeneration [7, 8]. Due to their availability and feasibility of harvest during tooth extraction, PDLSCs may become an ample source of stem cells, though limitation still exists [9]. A latest randomized clinical trial testified the clinical efficacy of PDLSCs, but results about clinical parameters showed no significance compared to the control group (with bone filling material only) [9]
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