Jaw Periosteum-Derived Mesenchymal Stem Cells Regulate THP-1-Derived Macrophage Polarization.

Fang He,Dorothea Alexander,Felix Umrath,Siegmar Reinert

doi:10.3390/ijms22094310

Fang He, Dorothea Alexander + Show 2 more

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https://doi.org/10.3390/ijms22094310

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Abstract

Mesenchymal stem cells from bone marrow have powerful immunomodulatory capabilities. The interactions between jaw periosteal cells (JPCs) and macrophages are not only relevant for the application of JPCs in regenerative medicine, but this understanding could also help treating diseases like osteonecrosis of the jaw. In previous studies, we analyzed, for the first time, immunomodulatory features of 2D- and 3D-cultured JPCs. In the present work, the effects of JPCs on the polarization state of macrophages in contact coculture were analyzed. To improve the macrophage polarization study, different concentrations of PMA (5 nM, 25 nM, and 150 nM) or different medium supplementations (10% FBS, 10% hPL and 5% hPL) were compared. Further, in order to analyze the effects of JPCs on macrophage polarization, JPCs and PMA-stimulated THP-1 cells were cocultured under LPS/IFN-γ or IL-4/IL-13 stimulatory conditions. Surface marker expression of M1 and M2 macrophages were analyzed under the different culture supplementations in order to investigate the immunomodulatory properties of JPCs. Our results showed that 5 nM PMA can conduct an effective macrophage polarization. The analyses of morphological parameters and surface marker expression showed more distinct M1/M2 phenotypes over FBS supplementation when using 5% hPL during macrophage polarization. In the coculture, immunomodulatory properties of JPCs improved significantly under 5% hPL supplementation compared to other supplementations. We concluded that, under the culture condition with 5% hPL, JPCs were able to effectively induce THP-1-derived macrophage polarization.

Highlights

For a successful application of tissue engineering products, including the implantation of biological scaffolds into recipients, an activation of host immune responses should be avoided in order to prevent implant rejection [1]
Thereafter, M0 macrophages were further differentiated into M1 or M2 macrophages by addition of LPS (15 ng/mL)/IFN-γ (20 ng/mL) or IL-4 (20 ng/mL)/IL-13 (20 ng/mL) for 24 or 72 h
When PMA concentrations of 5 or 25 nM were followed by 72 h for M1/M2-polarization, CD80 expression by M1 versus M2 macrophages was significantly increased compared to the results obtained after 24 h

Summary

Introduction

For a successful application of tissue engineering products, including the implantation of biological scaffolds into recipients, an activation of host immune responses should be avoided in order to prevent implant rejection [1]. The immunomodulatory functions of mesenchymal stem cells (MSCs), including the effective suppression of both innate and adaptive immunity [2,3], could be used to improve implant survival in the body. For bone regeneration in oral and maxillofacial surgery, jaw periosteal cells (JPCs) are a very promising stem cell source due to their high osteogenic potential and good accessibility. We described for the first time that JPCs possess similarities to bone marrow MSCs concerning their immunoregulatory functions [5,6].

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