scholarly journals High Dose IL-17A Enhances the Antiosteoarthritic Effect of Dental Pulp Mesenchymal Stem Cells by Reducing Inflammatory Response and Promoting Chondrocyte Proliferation

2021 ◽  
Author(s):  
Fu Bi qi ◽  
Zhou Yao ◽  
Long Wei ◽  
Cai Fen ◽  
Xia Qiang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Synovial Fluid ◽  
Inflammatory Response ◽  
Dental Pulp ◽  
Immune Modulation ◽  
High Dose ◽  
Chondrocyte Proliferation ◽  
Cytokine Assay

Abstract Objective: Mesenchymal stem cells (MSCs) have promising potential in regenerative therapy, partially through their potent immune modulation. The inflammatory cytokine IL-17A has been suggested to improve the therapeutic efficacy of MSCs. Herein, we determined whether pretreatment of dental pulp MSCs (DPMSCs) with IL-17A enhances the therapeutic potency of DPMSCs for osteoarthritis (OA).Methods: DPMSCs pretreated with IL-17A (0-75 ng/ml) were co-cultured with T lymphocytes for cytokine assay. In a rat OA model, DPMSCs pretreated with IL-17A were evaluated for antiosteoarthritic activity. Rat knee joints were harvested for color Doppler ultrasonography and histological staining, and synovial fluid was collected for cytokine assay. Additionally, chondrocytes isolated form joint cartilage of OA rats were co-cultured with IL-17A-pretreated DPMSCs for cell proliferation assay.Results: DPMSCs demonstrated a pluripotent capacity to differentiate into osteocytes, adipocytes, and chondrocytes. For in vitro co-culture, although DPMSCs pretreated with low dose of IL-17A (25 ng/ml) had inflammation-promoting effect, indicated by increased IL-2 and TNF-α secretion and decreased IL-4 release, high dose IL-17A (75 ng/ml) pretreatment enhanced the anti-inflammatory activity of DPMSCs. In vivo, high dose IL-17A-pretreated DPMSCs showed a stronger antiosteoarthritic activity than untreated DPMSCs, indicated by significantly reducing joint swelling, synovial fluid formation, the OARSI scores, and the production of inflammatory cytokines in synovial fluid. Besides, high dose IL-17A- pretreated DPMSCs enhanced the stimulatory activity of DPMSCs in chondrocyte proliferation in vitro.Conclusion: high dose IL-17A enhances the immunosuppressive property of DPMSCs, which helps alleviate osteoarthritis by inhibiting inflammatory response and promoting chondrocyte proliferation in the affected joints.

Comparing the osteogenic potential of schneiderian membrane and dental pulp mesenchymal stem cells: an in vitro study

2021 ◽  
Author(s):  
Antoine Berbéri ◽  
Joseph Sabbagh ◽  
Rita Bou Assaf ◽  
Michella Ghassibe-Sabbagh ◽  
Fatima Al-Nemer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dental Pulp ◽  
In Vitro Study ◽  
Vitro Study ◽  
Osteogenic Potential ◽  
Schneiderian Membrane

scholarly journals Dental Pulp-Derived Mesenchymal Stem Cells for Modeling Genetic Disorders

2021 ◽  
Vol 22 (5) ◽  
pp. 2269
Author(s):  
Keiji Masuda ◽  
Xu Han ◽  
Hiroki Kato ◽  
Hiroshi Sato ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dental Pulp ◽  
Genetic Disorders ◽  
In Vitro Models ◽  
High Plasticity ◽  
Human Teeth ◽  
Clinical Diagnoses ◽  
Models Of Disease

A subpopulation of mesenchymal stem cells, developmentally derived from multipotent neural crest cells that form multiple facial tissues, resides within the dental pulp of human teeth. These stem cells show high proliferative capacity in vitro and are multipotent, including adipogenic, myogenic, osteogenic, chondrogenic, and neurogenic potential. Teeth containing viable cells are harvested via minimally invasive procedures, based on various clinical diagnoses, but then usually discarded as medical waste, indicating the relatively low ethical considerations to reuse these cells for medical applications. Previous studies have demonstrated that stem cells derived from healthy subjects are an excellent source for cell-based medicine, tissue regeneration, and bioengineering. Furthermore, stem cells donated by patients affected by genetic disorders can serve as in vitro models of disease-specific genetic variants, indicating additional applications of these stem cells with high plasticity. This review discusses the benefits, limitations, and perspectives of patient-derived dental pulp stem cells as alternatives that may complement other excellent, yet incomplete stem cell models, such as induced pluripotent stem cells, together with our recent data.

scholarly journals Melatonin Inhibits the Ferroptotic Pathway in Rat Bone Marrow Mesenchymal Stem Cells by Activating the PI3K-AKT-mTOR Signaling Axis to Attenuate Steroid-induced Osteoporosis

2021 ◽  
Author(s):  
meng li ◽  
ning yang ◽  
li hao ◽  
wei zhou ◽  
lei li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
High Dose ◽  
Treatment Pathways ◽  
Marrow Mesenchymal Stem Cells

Abstract ObjectivesSteroid-induced osteoporosis (SIOP) is a secondary osteoporosis, which is a systemic bone disease characterized by low bone mass, bone microstructure damage, increased bone fragility, and easy fracture. However, the specific mechanism remains unclear. Glucocorticoid-induced death of osteoblasts and bone marrow mesenchymal stem cells (BMSCs) is an important factor in SIOP. Ferroptosis is an iron-dependent programmed cell death that differs from apoptosis, cell necrosis, and autophagy, which can be induced by many factors. Herein, we aimed to explore whether glucocorticoids (GCs) cause ferroptosis in BMSCs and determine possible treatment pathways and mechanisms of action. Melatonin (MT), a hormone secreted by the pineal gland, displays strong antioxidant abilities to scavenge free radicals and alleviates ferroptosis in many tissues and organs. MethodsIn this study, we used high-dose dexamethasone (DEX) to observe whether glucocorticoids induced ferroptosis in BMSCs. We then assessed whether MT can inhibit the ferroptotic pathway, thereby providing early protection against GC-induced SIOP, and investigated the signaling pathways involved.ResultsIn vitro experiments showed that MT intervention significantly improved GC-induced ferroptosis in BMSCs and significantly improved SIOP in vivo. Pathway analysis showed that MT improves ferroptosis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis. MT upregulates expression of PI3K, which is an important regulator of ferroptosis resistance. PI3K activators mimic the anti-ferroptosis effect of MT, but after blocking the PI3K pathway, the effect of MT is weakened. Obviously, MT can protect against SIOP induced by GC. Notably, even after GC-induced ferroptosis begins, MT can confer protection against SIOP. ConclusionOur research confirms that GC-induced ferroptosis is closely related to SIOP. Melatonin can inhibit ferroptosis by activating the PI3K-AKT-mTOR signaling pathway, thereby reducing the occurrence of steroid-induced osteoporosis. Therefore, MT may provide a novel strategy for preventing and treating SIOP.

scholarly journals Effect of Silicon, Titanium, and Zirconium Ion Implantation on NiTi Biocompatibility

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
L. L. Meisner ◽  
A. I. Lotkov ◽  
V. A. Matveeva ◽  
L. V. Artemieva ◽  
S. N. Meisner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Mesenchymal Stem Cells ◽  
Ion Implantation ◽  
Cell Counting ◽  
High Dose ◽  
Surface Layers ◽  
Test Flow ◽  
Ion Implanted

The objective of the work was to study the effect of high-dose ion implantation (HDII) of NiTi surface layers with Si Ti, or Zr, on the NiTi biocompatibility. The biocompatibility was judged from the intensity and peculiarities of proliferation of mesenchymal stem cells (MSCs) on the NiTi specimen surfaces treated by special mechanical, electrochemical, and HDII methods and differing in chemical composition, morphology, and roughness. It is shown that the ion-implanted NiTi specimens are nontoxic to rat MSCs. When cultivated with the test materials or on their surfaces, the MSCs retain the viability, adhesion, morphology, and capability for proliferationin vitro, as evidenced by cell counting in a Goryaev chamber, MTT test, flow cytometry, and light and fluorescence microscopy. The unimplanted NiTi specimens fail to stimulate MSC proliferation, and this allows the assumption of bioinertness of their surface layers. Conversely, the ion-implanted NiTi specimens reveal properties favorable for MSC proliferation on their surface.

scholarly journals Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammed Zayed ◽  
Steven Newby ◽  
Nabil Misk ◽  
Robert Donnell ◽  
Madhu Dhar
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Articular Cartilage ◽  
Synovial Fluid ◽  
Cartilage Repair ◽  
Cartilage Regeneration ◽  
Large Animal

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.

The role of micro-vibration parameters in inflammatory responses of macrophages cultured on biphasic calcium phosphate ceramics and the resultant influence on osteogenic differentiation of mesenchymal stem cells

2021 ◽  
Author(s):  
Jinjie Wu ◽  
Yitao Tang ◽  
Ximing Pu ◽  
Menglu Wang ◽  
Fuying Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Response ◽  
Biphasic Calcium Phosphate ◽  
Inflammatory Responses ◽  
Mechanical Stimuli ◽  
Micro Vibration ◽  
Vibration Parameters

Despite in vitro studies have shown that biomaterials and mechanical stimuli can mediate the inflammatory response or regulate osteogenesis of MSCs, the underlying behaviour for inflammatory response of macrophages on...

scholarly journals Eradication of specific donor-dependent variations of mesenchymal stem cells in immunomodulation to enhance therapeutic values

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Chunxue Zhang ◽  
Liqiang Zhou ◽  
Zhen Wang ◽  
Wenxia Gao ◽  
Wei Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Modulation ◽  
Human Umbilical Cord ◽  
Immune Functions ◽  
Two Factors ◽  
Ifn Γ ◽  
Pre Treatment

AbstractMesenchymal stem cells (MSCs) are one of the most widely clinically trialed stem cells, due to their abilities to differentiate into multiple cell lineages, to secrete regenerative/rejuvenative factors, and to modulate immune functions, among others. In this study, we analyzed human umbilical-cord-derived MSCs from 32 donors and revealed donor-dependent variations in two non-correlated properties, (1) cell proliferation, and (2) immune modulatory functions in vitro and in vivo, which might explain inconsistent clinical efficacies of MSCs. Through unbiased transcriptomic analyses, we discovered that IFN-γ and NF-κB signaling were positively associated with immune modulatory function of MSCs. Activation of these two pathways via IFN-γ and TNF-α treatment eradicated donor-dependent variations. Additional transcriptomic analyses revealed that treatment with these two factors, while having abolished donor-dependent variations in immune modulatory function, did not overall make different donor-derived MSCs the same at whole transcriptomic levels, demonstrating that the cells were still different in many other biological perspectives, and may not perform equally for therapeutic purposes other than immune modulation. Pre-selection or pre-treatment to eradicate MSC variations in a disease-treatment-specific manner would therefore be necessary to ensure clinical efficacies. Together this study provided novel insights into the quality control perspective of using different-donor-derived MSCs to treat inflammation-related clinical conditions and/or autoimmune diseases.

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