Macrophage polarization in periodontal ligament stem cells enhanced periodontal regeneration

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

The 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.

Methods

A 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.

Results

Elevated 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.

Conclusions

PDLSCs 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.

Related collections

Most cited references 26

Record: found
Abstract: found
Article: not found

Modulation of macrophage phenotype by cell shape.

Frances Y. McWhorter, Tingting Wang, Phoebe A. Nguyen … (2013)

Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment. Although much is known about how soluble factors influence macrophage polarization, relatively little is known about how physical cues present in the extracellular environment might modulate proinflammatory (M1) vs. prohealing (M2) activation. Specifically, the role of cell shape has not been explored, even though it has been observed that macrophages adopt different geometries in vivo. We and others observed that macrophages polarized toward different phenotypes in vitro exhibit dramatic changes in cell shape: M2 cells exhibit an elongated shape compared with M1 cells. Using a micropatterning approach to control macrophage cell shape directly, we demonstrate here that elongation itself, without exogenous cytokines, leads to the expression of M2 phenotype markers and reduces the secretion of inflammatory cytokines. Moreover, elongation enhances the effects of M2-inducing cytokines IL-4 and IL-13 and protects cells from M1-inducing stimuli LPS and IFN-γ. In addition shape- but not cytokine-induced polarization is abrogated when actin and actin/myosin contractility are inhibited by pharmacological agents, suggesting a role for the cytoskeleton in the control of macrophage polarization by cell geometry. Our studies demonstrate that alterations in cell shape associated with changes in ECM architecture may provide integral cues to modulate macrophage phenotype polarization.

0 comments Cited 444 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences.

Robert Stout, Chuancang Jiang, Bharati Matta … (2005)

Recent studies have described the development of distinct functional subsets of macrophages in association with cancer, autoimmune disease, and chronic infections. Based on the ability of Th1 vs Th2 cytokines to promote opposing activities in macrophages, it has been proposed that macrophages develop into either type 1 inflammatory or type 2 anti-inflammatory subsets. As an alternative to the concept of subset development, we propose that macrophages, in response to changes in their tissue environment, can reversibly and progressively change the pattern of functions that they express. As demonstrated herein, macrophages can reversibly shift their functional phenotype through a multitude of patterns in response to changes in cytokine environment. Macrophages display distinct functional patterns after treatment with IFN-gamma, IL-12, IL-4, or IL-10 and additional functional patterns are displayed depending on whether the cytokine is present alone or with other cytokines and whether the cytokines are added before or concomitantly with the activating stimulus (LPS). Sequential treatment of macrophages with multiple cytokines results in a progression through multiple functional phenotypes. This ability to adapt to changing cytokine environments has significant in vivo relevance, as evidenced by the demonstration that macrophage functional phenotypes established in vivo in aged or tumor-bearing mice can be altered by changing their microenvironment. A concept of functional adaptivity is proposed that has important implications for therapeutic targeting of macrophages in chronic diseases that result in the dominance of particular functional phenotypes of macrophages that play a significant role in disease pathology.

0 comments Cited 260 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Mesenchymal stem cell-macrophage crosstalk and bone healing

Yusuke Kohno, Masahiro Maruyama, Karthik Nathan … (2018)

Recent research has brought about a clear understanding that successful fracture healing is based on carefully coordinated cross-talk between inflammatory and bone forming cells. In particular, the key role that macrophages play in the recruitment and regulation of the differentiation of mesenchymal stem cells (MSCs) during bone regeneration has been brought to focus. Indeed, animal studies have comprehensively demonstrated that fractures do not heal without the direct involvement of macrophages. Yet the exact mechanisms by which macrophages contribute to bone regeneration remain to be elucidated. Macrophage-derived paracrine signaling molecules such as Oncostatin M, Prostaglandin E2 (PGE2), and Bone Morphogenetic Protein-2 (BMP2) have been shown to play critical roles; however the relative importance of inflammatory (M1) and tissue regenerative (M2) macrophages in guiding MSC differentiation along the osteogenic pathway remains poorly understood. In this review, we summarize the current understanding of the interaction of macrophages and MSCs during bone regeneration, with the emphasis on the role of macrophages in regulating bone formation. The potential implications of aging to this cellular cross-talk are reviewed. Emerging treatment options to improve facture healing by utilizing or targeting MSC-macrophage crosstalk are also discussed.

0 comments Cited 260 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Lang Lei: 86-25-83620252 , leilangdental@163.com

Fuhua Yan:

ORCID: http://orcid.org/0000-0002-6963-3530

86-25-83620252 , yanfh@nju.edu.cn

Journal

Journal ID (nlm-ta): Stem Cell Res Ther

Journal ID (iso-abbrev): Stem Cell Res Ther

Title: Stem Cell Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1757-6512

Publication date (Electronic): 15 November 2019

Publication date PMC-release: 15 November 2019

Publication date Collection: 2019

Volume: 10

Electronic Location Identifier: 320

Affiliations

[1 ]ISNI 0000 0001 2314 964X, GRID grid.41156.37, Department of Periodontology, , Nanjing Stomatological Hospital, Medical School of Nanjing University, ; Nanjing, 210008 China

[2 ]ISNI 0000 0001 2314 964X, GRID grid.41156.37, Department of Orthodontics, , Nanjing Stomatological Hospital, Medical School of Nanjing University, ; Nanjing, 210008 China

Author information

Fuhua Yan http://orcid.org/0000-0002-6963-3530

Article

Publisher ID: 1409

DOI: 10.1186/s13287-019-1409-4

PMC ID: 6858751

PubMed ID: 31730019

SO-VID: bad0e9f8-8856-4e61-b960-e3f09b2ef2aa

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 6 June 2019

Date revision received : 23 August 2019

Date accepted : 4 September 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81771078

Award Recipient : Fuhua Yan

Funded by: the Project of Invigorating Health Care through Science, Technology and Education, Jiangsu Provincial Medical Innovation Team

Award ID: CXTDB2017014

Award Recipient : Fuhua Yan

Funded by: Nanjing Medical Science and Technique Development Foundation

Award ID: QRX17081

Award Recipient : Lang Lei

Custom metadata

ScienceOpen disciplines: Molecular medicine

Keywords: periodontal ligament stem cells,macrophage polarization,periodontal regeneration

Data availability:

ScienceOpen disciplines: Molecular medicine

Keywords: periodontal ligament stem cells, macrophage polarization, periodontal regeneration

Macrophage polarization in periodontal ligament stem cells enhanced periodontal regeneration

Read this article at

Abstract

Background

Methods

Results

Conclusions

Related collections

Stress signalling in stem cells

Most cited references 26

Modulation of macrophage phenotype by cell shape.

Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences.

Mesenchymal stem cell-macrophage crosstalk and bone healing

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 231

Cited by 49

Most referenced authors 679