The secretome of periodontal ligament stem cells from MS patients protects against EAE

Rajan, Thangavelu Soundara; Giacoppo, Sabrina; Diomede, Francesca; Ballerini, Patrizia; Paolantonio, Michele; Marchisio, Marco; Piattelli, Adriano; Bramantı, Placido; Mazzon, Emanuela; Trubiani, Oriana

doi:10.1038/srep38743

Cited by 95 publications

(103 citation statements)

References 64 publications

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“…The potential use of the MSC-derived secretome in the treatment of MS has received a great deal of interest in recent years (10, 34). In view of this, the secretome is a promising candidate for a novel cell-free therapy that allows us to overcome the limitations and risks of cell-based therapies, including immune incompetency, carcinogenicity, condition for ex vivo cell expansion, and cost (35).…”

Section: Discussionmentioning

confidence: 99%

“…We recently demonstrated the immunosuppressive role of human periodontal ligament stem cell (hPDLSC)–derived conditioned medium (CM) and purified exosomes in experimental autoimmune encephalomyelitis (EAE), a murine model of MS (10). A large body of evidence suggests that paracrine mechanisms mediated by soluble factors that are released from MSCs play an important role in improving disease progression (11–13).…”

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confidence: 99%

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Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

Giacoppo

Rajan

Diomede³

et al. 2017

The FASEB Journal

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Recent research has widely investigated the anti-inflammatory effects of mesenchymal stem cells and their secretory products, termed the secretome, in the treatment of multiple sclerosis (MS). The present study examined the capacity of the conditioned medium (CM) from human periodontal ligament stem cells (hPLSCs) under hypoxia (H-hPDLSCs-CM) to suppress experimental autoimmune encephalomyelitis (EAE), a murine model of MS. To induce EAE, female C57BL/6 mice were immunized with myelin oligodendroglial glycoprotein peptide35–55. At the onset of symptoms, H-hPDLSCs-CM was infused via the tail vein of mice. Our results demonstrate the efficacy of H-hPDLSCs-CM treatment in diminishing clinical and histologic disease score. A key finding from this study is the marked expression of anti-inflammatory cytokine IL-37, paralleled by the suppression of proinflammatory cytokines in mice with EAE that were treated with H-hPDLSCs-CM. In addition, a consequent modulation of oxidative stress, autophagic, and apoptotic markers was observed in mice with EAE after hPDLSCs-CM administration. In addition, to provide additional evidence of the molecular mechanisms that underlie H-hPDLSCs-CM, we investigated its therapeutic action in scratch injury–exposed NSC-34 neurons, an in vitro model of injury. This model reproduces severe inflammation and oxidative stress conditions as observed after EAE damage. In vitro results corroborate the ability of hPDLSCs-CM to modulate inflammatory, oxidative stress, and apoptotic pathways. Taken together, our findings suggest H-hPDLSCs-CM as a new pharmacologic opportunity for the management of MS.—Giacoppo, S., Thangavelu, S. R., Diomede, F., Bramanti, P., Conti, P., Trubiani, O., Mazzon, E. Anti-inflammatory effects of hypoxia-preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL-37.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

Giacoppo

Rajan

Diomede³

et al. 2017

The FASEB Journal

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“…Total RNA was isolated from CTR‐GMSCs and SC‐GMSCs cultured for 1 week using the Total RNA Purification Kit (Norgen Biotek Corp., Ontario, CA) according to the manufacturer's instructions. Total RNA was quantified by means BioSpectrometer (Eppendorf, Milan, Italy) using μCuvette G1.0 (Eppendorf) …”

Section: Methodsmentioning

confidence: 99%

Transcriptomic analysis of gingival mesenchymal stem cells cultured on 3D bioprinted scaffold: A promising strategy for neuroregeneration

Gugliandolo

Diomede

Cardelli

et al. 2017

J Biomedical Materials Res

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The combined approach of mesenchymal stem cells (MSCs) and scaffolds has been proposed as a potential therapeutic tool for the treatment of neurodegenerative diseases. Indeed, even if MSCs can promote neuronal regeneration, replacing lost neurons or secreting neurotrophic factors, many limitations still exist for their application in regenerative medicine, including the low survival and differentiation rate. The scaffolds, by mimicking the endogenous microenvironment, have shown to promote cell survival, proliferation, and differentiation. In this work, gingival mesenchymal stem cells (GMSCs), isolated from healthy donors, were expanded in vitro, by culturing them adherent in plastic dishes (CTR-GMSCs) or on a poly(lactic acid) scaffold (SCGMSCs). In order to evaluate the survival and the neurogenic differentiation potential, we performed a comparative transcriptomic analysis between CTR-GMSCs and SC-GMSCs by next generation sequencing. We found that SC-GMSCs showed an increased expression of neurogenic and prosurvival genes. In particular, genes involved in neurotrophin signaling and PI3K/Akt pathways were upregulated. On the contrary, proapoptotic and negative regulator of neuronal growth genes were downregulated. Moreover, nestin and GAP-43 protein levels increased in SC-GMSCs, confirming the neurogenic commitment of these cells. In conclusion, the scaffold, providing a trophic support for MSCs, may promote GMSCs differentiation toward a neuronal phenotype and survival.

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“…Human PDLSCs show proteins associated to the growth, regulation, and genesis of neuronal cells, in agreement with their neural crest origin (Trubiani, Guarnieri, et al, ). The transplantation of hPDLSCs may represent a putative novel and helpful tool for multiple sclerosis treatment (Rajan, Giacoppo, Diomede, et al, ; Trubiani, Giacoppo, et al, ). The periodontal ligament biopsy, obtained by scraping the alveolar crest and the horizontal fibers of the root, is apt to find an elevated number of autologous stem cells with genomic stability and capacity to differentiate into ecto‐mesenchymal lineages (Trubiani et al, ).…”

Section: Discussionmentioning

confidence: 99%

Endothelial committed oral stem cells as modelling in the relationship between periodontal and cardiovascular disease

Pizzicannella

Diomede

Merciaro

et al. 2018

Journal Cellular Physiology

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In the present study we have mimicked, in vitro, an inflammatory process using Lipopolysaccharide derived from Porphyromonas Gingivalis (LPS-G) and human Periodontal Ligament Stem Cells induced to endothelial differentiation (e-hPDLSCs). The research project has been organized into the three following steps: i) induction of hPDLSCs toward endothelial differentiation; ii) evaluation of the molecular signaling pathway involved in the response to the LPS-G, and iii) functional response evaluation of the living construct constituted by porcine decellularized valve/e-hPDLSCs treated with LPS-G. Obtained results showed that 5 μg/ml LPS-G stimulus provokes: a slowdown of cell growth starting from 24 hr and the release of IL6, IL8, and MCP1 molecules. Signaling network analyzed showed the activation of TLR4/ NFkB/ERK1/2/p-ERK1/2 signaling mediated by MyD88 in LPS-G stimulated e-hPDLSCs, moreover a time course put in evidence a nuclear traslocation of ERK1/2 and p-ERK1/2 in differentiated samples. Following, the ability of e-hPDLSCs to expand and colonize the decellularized porcine heart valves was appraised at ultrastructural level. Considering that, the Reactive Oxygen Species (ROS) play an important role in the progression and development of cardiovascular disease (CVD), in LPS-G living construct model e-hPDLSCs/decellularized porcine heart valves (dPHV), ROS production was assessed. Time lapse experiments evidenced that LPS-G provokes in e-hPDLSCs a rapid and sustained increase in ROS generation, negligible on undifferentiated cells. From obtained data, by multiparametric analyses, a reasonable conclusion may be that the inflammation process activated by LPS-G can affect endothelial cells and could represent in vivo a possible pathological and predictor state of CVD.

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The secretome of periodontal ligament stem cells from MS patients protects against EAE

Cited by 95 publications

References 64 publications

Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

Transcriptomic analysis of gingival mesenchymal stem cells cultured on 3D bioprinted scaffold: A promising strategy for neuroregeneration

Endothelial committed oral stem cells as modelling in the relationship between periodontal and cardiovascular disease

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