Research Article
Print
Research Article
The effect of conditioned medium isolated from dental pulp mesenchymal stem cells (DPSC) treated with curcumin on oral pathogens
expand article infoMohsen Safaei‡, Razieh Souri‡, Saba Siabani‡, Motahare Ahmadvand‡, Ladan Jamshidy‡, Ling Shing Wong§, Fang Li|, Masoome Eivazi‡
‡ Kermanshah University of Medical Sciences, Kermanshah, Iran
§ INTI International University, Nilai, Malaysia
| Jiangsu Vocational College of Medicine, Yancheng, China

Corresponding author: Masoome Eivazi ( eivazimasoome@gmail.com )

Academic editor: Plamen Peikov
© 2024 Mohsen Safaei, Razieh Souri, Saba Siabani, Motahare Ahmadvand, Ladan Jamshidy, Ling Shing Wong, Fang Li, Masoome Eivazi.
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation: Safaei M, Souri R, Siabani S, Ahmadvand M, Jamshidy L, Wong LS, Li F, Eivazi M (2024) The effect of conditioned medium isolated from dental pulp mesenchymal stem cells (DPSC) treated with curcumin on oral pathogens. Pharmacia 71: 1-8. https://doi.org/10.3897/pharmacia.71.e132611
Open Access

Abstract

Objectives: The research sought to examine the antibacterial properties of the conditioned media derived from dental pulp mesenchymal stem cells (DPSC) that were treated with curcumin.

Methods: An investigation of the physicochemical characteristics of curcumin nanoparticles was conducted utilizing scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and mapping techniques. The optimal dose of curcumin for treating DPSC cells was determined using the MTT test. The study investigated the antioxidant properties of curcumin on DPSC cells by measuring ROS. Two groups were isolated, one without treatment (control) and the other treated with curcumin. The antibacterial and antifungal properties of the supernatant culture medium of DPSC cells were then investigated.

Results: The present study results indicate that curcumin possesses suitable physicochemical properties, including morphology and purity. Additionally, it exhibits no toxicity at doses ranging from 0 to 1.25 (μg/ml) and displays antioxidant properties at the IC50 concentration. Furthermore, it increases DPSCs. The antimicrobial results demonstrate that CM-CUR, at various concentrations, reduces the viability of Streptococcus mutans (S. mutans) and inhibits the growth of Candida albicans (C. albicans) by 85%.

Conclusion: The research results indicate that the combination of CM-CUR is suitable for antibacterial and antifungal applications in dentistry to enhance human health.

Keywords

dental pulp stem cells, curcumin, culture medium, antibacterial activity, antifungal activity, human health

Introduction

One of the main challenges of dealing with antibiotic resistance is the lack of sufficient information, especially in places where surveillance is minimal and data is scarce. Extensive research has been conducted to investigate the effects of antibiotic resistance on incidence, mortality, length of hospital stays, and health care costs, but there is no comprehensive estimate in this regard (Temkin et al. 2018; Cassini et al. 2019; Moradpoor et al. 2021). One of the main prerequisites for oral health is maintaining homeostasis of the host microbe in the oral cavity (Kantarci and Hasturk 2018; Freire et al. 2021; Nikkerdar et al. 2024). Many oral diseases, including caries and periodontal diseases, are related to disturbances in this homeostasis and dysbiosis (Andrukhov et al. 2022). The low rejection rates, ease of availability and isolation of stem cells, and in vitro culture methods contribute to making stem cell therapy superior to many other therapies (Lysaght et al. 2008). Mesenchymal stem cells (MSCs) have emerged as a new therapeutic strategy for treating bacterial diseases due to their documented bactericidal activity in laboratory studies (Goy et al. 2009). Another type of mesenchymal stem cell that is isolated from dental pulp tissue is DPSC (Samiei et al. 2021). Numerous experiments are underway to combine new scientific knowledge with traditional plant extracts, potentially leading to less toxic, cost-effective, and accessible natural alternative therapies. Currently, mesenchymal stem cell (MSC) lines are being treated with a mix of crude plant extracts and purified compounds to study their mechanisms and effects (Udalamaththa et al. 2016). Optimizing the potency and therapeutic benefits of MSCs is a priority. Several strategies were proposed to optimize stem cells, which are roughly divided into two categories, i.e., genetic modification and non-genetic modification (reactivations) (Li et al. 2022). Plant extracts contain a large amount of phytochemicals such as polyphenols, flavonoids, and other chemical substances derived from plants that synergistically help in the treatment of diseases (Di Giacomo et al. 2015). Curcumin, a natural compound found in turmeric, is renowned for its anti-proliferative effects in cancer treatment. Additionally, it exhibits antibacterial and antioxidant properties and promotes mineralization (Samiei et al. 2022). Many studies on the use of curcumin and its analogs related to its antimicrobial and antiparasitic properties in specific applications (e.g., wound healing, periodontal diseases, tuberculosis, Helicobacter pylori infection) have been conducted in the last decade. The recent ones have been published (Barua and Buragohain 2021; Ranjbar et al. 2021; Salehi et al. 2021). Considering the importance of dealing with microbial resistance in today’s era, our aim in conducting this study is to investigate the synergistic effect of curcumin with an isolated culture medium of dental pulp mesenchymal stem cells on S. mutans and C. albicans pathogens.

Materials and methods

Preparation of curcumin

In the present study, curcumin was purchased in a volume of 5 grams with the brand Bio Basic in commercial form with CAS# 458-37-7.

Characterization

In this study, scanning electron microscopy (SEM) and EDX analysis, along with MAP, were used to identify the distribution of elements, elemental distribution, and particle size of curcumin. The structural arrangement, surface topography, and constituent elements of the nanocomposite were investigated using SEM (TESCAN MIRA3) at an acceleration voltage of 30 kV. The number of constituent elements was determined by energy dispersive X-ray spectroscopy by the SAMX energy X-ray detector (EDX) in SEM.

Cell culture

Dental pulp mesenchymal stem cells (DPSC) were procured from the Pasteur Institute of Iran-Tehran. The cells were maintained under ideal cell culture conditions, such as a temperature of 37 degrees Celsius, 95% humidity, and a 5% CO2 atmosphere. For cell culture, DMEM-F12 culture medium supplemented with 10% (v/v) inactivated fetal calf serum (FBS) and 1% penicillin and streptomycin was used.

Cytotoxic study

In this study, the cytotoxicity of curcumin on DPSC cells was investigated using the MTT method. Briefly, in a 96-well plate, 20,000 cells were cultured in each well, and the final volume of each well was 200 μl. A CO2 incubator was used to keep the cells alive until they reached the appropriate density and morphology. Next, the cells were treated with concentrations of 0 to 20 micrograms/ml of curcumin separately for 24 hours (three wells were considered for each treatment). After the treatment period, the wells were emptied by inverting the plate on filter paper, and the cells were washed with PBS buffer (200 microliters per well). Subsequently, 100 microliters of MTT solution were added to each well, and the plate was incubated for 3–4 hours in the dark. After the incubation period, the MTT solution was removed, and 100 microliters of DMSO solution were added to each well. The plate was gently shaken to dissolve the crystals. The light absorption was measured at a wavelength of 570 nm. The average absorption rate of three wells for each treatment was calculated and compared with the control group. The IC50 concentration was then calculated using Prism software.

Intracellular ROS measurement

To investigate the antioxidant properties of curcumin at IC50 concentrations in DPSC cells, an ROS assay was used in these cells. Briefly, DPSC cells were treated with the IC50 concentration of curcumin for 24 hours after being cultured in six-well plates. After the desired treatment, 20 microliters of DCF reagent were added to the wells (groups treated with curcumin and the control group) and incubated for 45 minutes. After incubation, washing was done with PBS buffer, and 800 microliters of Triton-x100 were added to each well. After that, incubation was done at 4 °C for 30 minutes. After the end of the incubation period, the contents of the plates were transferred to a microtube and centrifuged at 13500 rpm for 15 minutes. Finally, the fluorescence of the samples was measured using a microplate reader (Bio-Tek, ELX 800, Winooski, VT) at an excitation wavelength of 488 nm and an emission wavelength of 510 nm.

Isolation of conditioned media

The supernatant culture medium was isolated from dental pulp mesenchymal stem cells and divided into two groups: the control group (supernatant culture medium isolated from cells not treated with curcumin [CM]) and the treatment group (supernatant culture medium isolated from cells treated with curcumin for 24 hours [CM-CUR]). The objective was to investigate their antibacterial properties. In short, the cell culture medium of mesenchymal stem cells after culture in the third passage, when the cells reached the appropriate density, was replaced with less FBS, and this step was repeated every 2 to 3 days, and the mesenchymal stem cells were gradually less cultured. Therefore, the cells were successively adapted to the serum-free environment, and the creation of unwanted proteins caused by oxidative stress-related changes was also prevented (Pouya et al. 2018). After cell adaptation to a serum-free environment, cells were treated with curcumin at IC50 concentrations for 24 hours, and their supernatant was slowly separated and filtered with 0.22-micrometer filters. The supernatant culture medium obtained was kept at -70 °C for use in further study. A supernatant culture medium of dental pulp mesenchymal cells without treatment with curcumin was used as a control group.

Antibacterial activity

The antibacterial effect of supernatant culture medium isolated from dental pulp mesenchymal stem cells treated with curcumin was investigated against S. mutans biofilm. The studied bacteria (ATCC 35668) were purchased from a Persian-type culture collection in Iran. Single colonies of S. mutans were cultured on a brain-heart infusion agar medium for 24 hours. A bacterial suspension equivalent to 0.5 McFarland was added to a 96-well culture plate and incubated at 37 °C for 72 hours to form a bacterial biofilm. Every 24 hours, the culture medium was replaced with a fresh brain-heart infusion containing 2% sucrose and 1% mannose. After the formation of biofilm, washing with PBS was done to remove the planktonic. In the following, the separated culture mediums in curcumin and control treatment groups were added separately to the wells, and the 96-well plates were incubated for 24 hours at 37 °C. Next, to measure the number of living cells in biofilms, the cells were gently separated from the bottom of the wells and collected. Next, the vortex was used for 2 minutes to homogenize the obtained cell suspension. To measure colony-forming units (CFU), bacterial suspensions were serially diluted ten times, cultured on heart-brain infusion agar plates, and incubated for 24 hours at 37 °C. After incubation, the plates were heated, and the colonies were counted to calculate the average. All experiments were conducted in triplicate (Imani et al. 2021; Safaei and Moghadam 2022).

Statistical analysis

In the study, data analysis was performed using the SPSS software package (Version 26), which is compatible with Windows 10. Statistical significance between groups was evaluated using either a two-tailed Student’s t-test or a two-way ANOVA. The results were reported as mean values ± standard deviation (SD), and differences were considered significant for a P-value less than 0.05.

Results

SEM analysis

In the present study, an SEM test was used to check the morphology and size of the curcumin particles used. The obtained results showed that the curcumin used has a flat rod structure, and the edges of the particles are distinct and uniform. In addition, curcumin particles appear to be flat and rod-shaped, but in very small sizes. The obtained results are shown in Fig. 1.

Figure 1. 

SEM image of curcumin.

EDX analysis

In this study, the results of the EDX elemental analysis of curcumin are presented in Fig. 2. The obtained results showed the presence of carbon and oxygen by displaying carbon and oxygen peaks without any other indicator peaks. Therefore, the results show that the curcumin sample used does not contain any other elements and is free of any impurities.

Figure 2. 

EDX diagram of curcumin.

MAP analysis

The results of the MAP test confirmed the presence of oxygen and carbon elements in the curcumin used with the X-ray energy diffraction spectroscopy pattern. The obtained results are shown in Fig. 3.

Figure 3. 

MAP images of curcumin.

MTT assay

The MTT test was used to determine the optimal concentration for the treatment of dental pulp stem cells (DPSC) with curcumin. The obtained results showed that curcumin up to a concentration of 1.25 micrograms/ml is non-toxic for DPSC cells, and in a period of 24 hours, the cells can be treated at this concentration, and the cells in this period will show a concentration of maximum life (Fig. 4). It was also shown that at concentrations higher than 2.5 μg/ml, curcumin was toxic for DPSC cells, and the cells showed less than 50% survival. Fig. 4 shows the graph related to the MTT test.

Figure 4. 

MTT assay. Investigating the effect of different concentrations of curcumin on dental pulp stem cells (DPSC cell line).

ROS measurement

To investigate the effect of curcumin on the amount of ROS changes in DPSC cells, the ROS measurement test using DCF reagent was used (Fig. 5). The obtained results showed that curcumin at the IC50 concentration did not have any pro-oxidant properties in these cells; it did not cause an increase in ROS in these cells compared to the control group. In addition, it was shown that the treatment of DPSC cells with curcumin at IC50 concentration caused a slight decrease in the amount of intracellular ROS compared to the control group. This decrease was statistically significant (P<0.05).

Figure 5. 

Investigation of ROS level changes in dental pulp stem cells after treatment with different concentrations of curcumin for 24 hours. Data as (Mean ± SEM, n = 6). *P < 0.05, versus the control group.

Antibacterial assay

The antibacterial properties of CM-CUR against the bacterial biofilm of S. mutans in different concentrations were investigated in volume-volume (V/V) form, and the results showed that CM-CUR compared to CM (the control group) in a dependent manner. The dose inhibited the growth of S. mutans bacteria. The obtained results showed that CM-CUR at the highest concentration reduced the survival rate of S. mutans bacteria to 0.89%, which significantly reduced the survival rate compared to the control group. The obtained results are shown in Fig. 6.

Figure 6. 

Antibacterial effect of different concentrations of CM-CUR-NP against Streptococcus mutans bacteria. Data as (Mean ± SEM, n = 6).

Antifungal assay

The antifungal properties of CM-CUR against the C. albicans fungus were analyzed in different concentrations in volume-volume (V/V) form (Fig. 7). The results obtained showed that CM-CUR inhibited the growth of C. albicans in a dose-dependent manner. Our results showed that CM-CUR showed its inhibitory effect at the highest volume-volume (v/v) concentration of 85%, which was very impressive compared to the control group.

Figure 7. 

Antifungal activity of concentrations of CM-CUR against Candida albicans. Data as (Mean ± SEM, n = 6).

Discussion

Antimicrobial resistance is a significant concern across clinical populations, with limited treatment options for affected individuals. This resistance often stems from the unnecessary or excessive use of antimicrobials, as well as incorrect dosages or durations of treatment. Proper antimicrobial stewardship is crucial in combating this growing issue (Guardabassi et al. 2018). The overuse of broad-spectrum antibiotics underscores the importance of exploring and developing alternative treatments to combat diseases effectively while reducing the risk of antimicrobial resistance (Martin et al. 2015). Mesenchymal stem cells (MSCs) have indeed shown promising antimicrobial properties through various mechanisms, both indirect and direct. This underscores their potential in therapeutic applications beyond traditional roles (Meisel et al. 2011; Gupta et al. 2012). A recent study demonstrated the in vitro antimicrobial activity of mesenchymal stem cells (MSCs) against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) (Krasnodembskaya et al. 2010). In proof-of-concept studies, mesenchymal stem cells (MSCs) have exhibited strong synergy with current antibiotic treatments to effectively penetrate biofilm infections (Johnson et al. 2017). as well as the capacity to act as antifungals (Arango et al. 2018). Preconditioning, also referred to as activation or priming, involves exposing MSCs to various culture conditions to modulate or enhance specific desirable characteristics of the cells (Cahuascanco et al. 2019; Yagi et al. 2020). In this research, by preconditioning dental pulp mesenchymal stem cells using curcumin, we investigated the antimicrobial properties of the culture medium of these cells compared to normal stem cells (not treated with curcumin). One of the essential features of curcumin that affects the differentiation of osteoblasts is its antioxidant potential and inhibition of free radicals. Oxidative stress prevents the osteoblastic differentiation of MSCs. However, curcumin’s antioxidant properties reduce oxidative stress and protect stem cells from oxidative damage (Gorabi et al. 2019). Our study also showed that the treatment of dental pulp stem cells with curcumin has improved the antioxidant properties of these cells compared to untreated cells. Studies have shown that doses of 0.5 to 1 μg/ml in 24 hours are the most favorable doses of curcumin for the treatment of mesenchymal stem cells of the dental pulp, which was also confirmed in our study (Samiei et al. 2021). In addition, changing environmental conditions play a significant role in influencing the function and behavior of mesenchymal stem cells, as demonstrated in various research studies. The results of various research studies at the cellular and molecular levels demonstrated that the differentiation of dental pulp stem cells (DPSC) increased significantly in the presence of curcumin. This effect was accompanied by the increased expression of bone markers, including Runx-2 and OCN 21, a few days after the treatment. This has been demonstrated. Additionally, it was observed that the level of osteogenic proteins was higher post-translationally, which indicates the potential role of curcumin in the induction of DPSC differentiation at both the translational and transcriptional stages (Ghavimi et al. 2020; Khezri et al. 2021). A study demonstrated that curcumin, both alone and in conjunction with calcitriol, enhanced the activity of the ALP gene and the specific mRNA expression of osteoblast ALP when DPSCs were cultured in an osteogenic environment. The administration of calcitriol alone resulted in a more pronounced increase in enzyme activity compared to the combination with curcumin. These findings indicate that curcumin has the potential to facilitate the early osteogenic differentiation of DPSCs in a manner analogous to calcitriol, which is recognized as a powerful stimulator of osteogenesis (Samiei et al. 2021). In a study in 2023, Haj Momeni et al. significantly improved the anti-cancer properties of the culture medium isolated from these cells by treating bone marrow mesenchymal stem cells with thymoquinone (Hajmomeni et al. 2023). Absolutely, antimicrobial proteins and polypeptides like lysozyme, lactoferrin, secretory leukoprotease inhibitors, and defensins are crucial in combating bacteria due to their ability to kill microorganisms. They play a significant role in our immune defense system (Rogan et al. 2006). Cathelicidins are indeed one of the main families of antimicrobial peptides found in mammals. These peptides play a vital role in the innate immune system by combating various pathogens like bacteria, fungi, and viruses (Zanetti 2005).

Cathelicidins, along with many other antimicrobial peptides, work by disrupting the integrity of bacterial membranes. This disruption leads to the destruction of the pathogen, making these peptides an important part of the body’s defense against microbial invaders (Gennaro and Zanetti 2000). hCAP-18/LL-37 is a well-known member of the cathelicidin family of antimicrobial peptides in humans. It is a 4 kDa peptide primarily produced by phagocytic leukocytes, epithelial cells, and even in the bone marrow. This versatile peptide plays a crucial role in the innate immune response by combating various pathogens through its antimicrobial activity (Frohm Nilsson et al. 1999) and is expressed by mesenchymal stem cells (Coffelt et al. 2009). The culture medium isolated from mesenchymal stem cells (MSCs) has been found to significantly inhibit bacterial growth compared to control medium or normal human lung fibroblasts (NHLF). Studies suggest that the antimicrobial activity of MSC culture medium against Gram-negative bacteria can be attributed to the presence of the human cathelicidin antimicrobial peptide hCAP-18/LL-37. Both mRNA and protein expression data demonstrate the role of LL-37 in this antimicrobial activity, highlighting its importance in the innate immune response (Krasnodembskaya et al. 2010).

Conclusion

This article reports the successful treatment of dental pulp stem cells with curcumin. The purity and quality of the curcumin used were determined by using physicochemical methods including SEM, EDX, and MAP. The optimal concentration of curcumin for the treatment of DPSC cells was obtained by the MTT method, which was shown to be non-toxic at concentrations of 0–25.1 μg/ml and also improved the antioxidant properties of these cells. Our results showed that treatment of DPSC cells with an IC50 concentration of curcumin improved the antimicrobial properties of CM isolated from these cells by changing the secreted proteins of these cells. More studies are suggested to investigate how curcumin works, the effect of curcumin on DPSC cells in improving antibacterial, antifungal, and antioxidant properties, and the signaling pathways involved in this regard.

References

  • Andrukhov O, Blufstein A, Behm C (2022) A review of antimicrobial activity of dental mesenchymal stromal cells: Is there any potential? Frontiers in Oral Health 2: 832976. https://doi.org/10.3389/froh.2021.832976
  • Arango JC, Puerta-Arias JD, Pino-Tamayo PA, Arboleda-Toro D, González Á (2018) Bone marrow-derived mesenchymal stem cells transplantation alters the course of experimental paracoccidioidomycosis by exacerbating the chronic pulmonary inflammatory response. Medical Mycology 56: 884–895. https://doi.org/10.1093/mmy/myx128
  • Cahuascanco B, Bahamonde J, Huaman O, Jervis M, Cortez J, Palomino J, Escobar A, Retamal P, Torres CG, Peralta OA (2019) Bovine fetal mesenchymal stem cells exert antiproliferative effect against mastitis causing pathogen Staphylococcus aureus. Veterinary Research 50: 25. https://doi.org/10.1186/s13567-019-0643-1
  • Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha A, Simonsen GS, Colomb-Cotinat M, Kretzschmar ME, Devleesschauwer B, Cecchini M, Ouakrim DA, Oliveira TC, Struelens MJ, Suetens C, Monnet DL (2019) Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. The Lancet Infectious Diseases 19: 56–66. https://doi.org/10.1016/S1473-3099(18)30605-4
  • Coffelt SB, Marini FC, Watson K, Zwezdaryk KJ, Dembinski JL, LaMarca HL, Tomchuck SL, zu Bentrup KH, Danka ES, Henkle SL, Scandurro AB (2009) The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proceedings of the National Academy of Sciences 106: 3806–3811. https://doi.org/10.1073/pnas.0900244106
  • Di Giacomo C, Vanella L, Sorrenti V, Santangelo R, Barbagallo I, Calabrese G, Genovese C, Mastrojeni S, Ragusa S, Acquaviva R (2015) Effects of Tithonia diversifolia (Hemsl.) A. Gray Extract on Adipocyte Differentiation of Human Mesenchymal Stem Cells. Vinciguerra M (Ed.). PLoS ONE 10: e0122320. https://doi.org/10.1371/journal.pone.0122320
  • Frohm Nilsson M, Sandstedt B, Sørensen O, Weber G, Borregaard N, Ståhle-Bäckdahl M (1999) The Human Cationic Antimicrobial Protein (hCAP18), a peptide antibiotic, is widely expressed in human squamous epithelia and colocalizes with Interleukin-6. McGhee JR (Ed.). Infection and Immunity 67: 2561–2566. https://doi.org/10.1128/IAI.67.5.2561-2566.1999
  • Ghavimi MA, Bani Shahabadi A, Jarolmasjed S, Memar MY, Maleki Dizaj S, Sharifi S (2020) Nanofibrous asymmetric collagen/curcumin membrane containing aspirin-loaded PLGA nanoparticles for guided bone regeneration. Scientific Reports 10: 18200. https://doi.org/10.1038/s41598-020-75454-2
  • Gorabi AM, Kiaie N, Hajighasemi S, Jamialahmadi T, Majeed M, Sahebkar A (2019) The Effect of Curcumin on the Differentiation of Mesenchymal Stem Cells into Mesodermal Lineage. Molecules 24: 4029. https://doi.org/10.3390/molecules24224029
  • Guardabassi L, Apley M, Olsen JE, Toutain P-L, Weese S (2018) Optimization of Antimicrobial Treatment to Minimize Resistance Selection. Aarestrup FM, Schwarz S, Shen J, Cavaco L (Eds). Microbiology Spectrum 6(3): 1–36. https://doi.org/10.1128/microbiolspec.ARBA-0018-2017
  • Gupta N, Krasnodembskaya A, Kapetanaki M, Mouded M, Tan X, Serikov V, Matthay MA (2012) Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia. Thorax 67: 533–539. https://doi.org/10.1136/thoraxjnl-2011-201176
  • Hajmomeni P, Sisakhtnezhad S, Bidmeshkipour A (2023) Thymoquinone-treated mouse mesenchymal stem cells-derived conditioned medium inhibits human breast cancer cells in vitro. Chemico-Biological Interactions 369: 110283. https://doi.org/10.1016/j.cbi.2022.110283
  • Imani MM, Kiani M, Rezaei F, Souri R, Safaei M (2021) Optimized synthesis of novel hydroxyapatite/CuO/TiO2 nanocomposite with high antibacterial activity against oral pathogen Streptococcus mutans. Ceramics International 47(23): 33398–33404. https://doi.org/10.1016/j.ceramint.2021.08.246
  • Johnson V, Webb T, Norman A, Coy J, Kurihara J, Regan D, Dow S (2017) Activated Mesenchymal Stem Cells Interact with Antibiotics and Host Innate Immune Responses to Control Chronic Bacterial Infections. Scientific Reports 7: 9575. https://doi.org/10.1038/s41598-017-08311-4
  • Kantarci A, Hasturk H (2018) Microbes and host response: A relationship between health and disease. Oral Diseases 24: 1385–1387. https://doi.org/10.1111/odi.12731
  • Khezri K, Maleki Dizaj S, Rahbar Saadat Y, Sharifi S, Shahi S, Ahmadian E, Eftekhari A, Dalir Abdolahinia E, Lotfipour F (2021) Osteogenic Differentiation of Mesenchymal Stem Cells via Curcumin-Containing Nanoscaffolds. Zhang D (Ed.). Stem Cells International 2021: 1–9. https://doi.org/10.1155/2021/1520052
  • Krasnodembskaya A, Song Y, Fang X, Gupta N, Serikov V, Lee J-W, Matthay MA (2010) Antibacterial Effect of Human Mesenchymal Stem Cells Is Mediated in Part from Secretion of the Antimicrobial Peptide LL-37. Stem Cells 28: 2229–2238. https://doi.org/10.1002/stem.544
  • Li M, Jiang Y, Hou Q, Zhao Y, Zhong L, Fu X (2022) Potential pre-activation strategies for improving therapeutic efficacy of mesenchymal stem cells: current status and future prospects. Stem Cell Research & Therapy 13: 146. https://doi.org/10.1186/s13287-022-02822-2
  • Lysaght MJ, Jaklenec A, Deweerd E (2008) Great Expectations: Private Sector Activity in Tissue Engineering, Regenerative Medicine, and Stem Cell Therapeutics. Tissue Engineering Part A 14: 305–315. https://doi.org/10.1089/tea.2007.0267
  • Martin MJ, Thottathil SE, Newman TB (2015) Antibiotics Overuse in Animal Agriculture: A Call to Action for Health Care Providers. American Journal of Public Health 105: 2409–2410. https://doi.org/10.2105/AJPH.2015.302870
  • Meisel R, Brockers S, Heseler K, Degistirici Ö, Bülle H, Woite C, Stuhlsatz S, Schwippert W, Jäger M, Sorg R, Henschler R, Seissler J, Dilloo D, Däubener W (2011) Human but not murine multipotent mesenchymal stromal cells exhibit broad-spectrum antimicrobial effector function mediated by indoleamine 2,3-dioxygenase. Leukemia 25: 648–654. https://doi.org/10.1038/leu.2010.310
  • Moradpoor H, Safaei M, Golshah A, Mozaffari HR, Sharifi R, Imani MM, Mobarakeh MS (2021) Green synthesis and antifungal effect of titanium dioxide nanoparticles on oral Candida albicans pathogen. Inorganic Chemistry Communications 130: 108748. https://doi.org/10.1016/j.inoche.2021.108748
  • Nikkerdar N, Golshah A, Salmani Mobarakeh M, Fallahnia N, Azizi B, Shoohanizad E, Souri R, Safaei M (2024) Recent progress in application of zirconium oxide in dentistry. Journal of Medicinal and Pharmaceutical Chemistry Research 6: 1042–1071. https://doi.org/10.48309/JMPCR.2024.432254.1069
  • Pouya S, Heidari M, Baghaei K, Asadzadeh Aghdaei H, Moradi A, Namaki S, Zali MR, Hashemi SM (2018) Study the effects of mesenchymal stem cell conditioned medium injection in mouse model of acute colitis. International Immunopharmacology 54: 86–94. https://doi.org/10.1016/j.intimp.2017.11.001
  • Rogan MP, Geraghty P, Greene CM, O’Neill SJ, Taggart CC, McElvaney NG (2006) Antimicrobial proteins and polypeptides in pulmonary innate defence. Respiratory Research 7: 29. https://doi.org/10.1186/1465-9921-7-29
  • Safaei M, Moghadam A (2022) Optimization of the synthesis of novel alginate-manganese oxide bionanocomposite by Taguchi design as antimicrobial dental impression material. Materials Today Communications 31: 103698. https://doi.org/10.1016/j.mtcomm.2022.103698
  • Salehi B, Rodrigues CF, Peron G, Dall’Acqua S, Sharifi‐Rad J, Azmi L, Shukla I, Singh Baghel U, Prakash Mishra A, Elissawy AM, Singab AN, Pezzani R, Redaelli M, Patra JK, Kulandaisamy Venil C, Das G, Singh D, Kriplani P, Venditti A, Fokou PVT, Iriti M, Amarowicz R, Martorell M, Cruz‐Martins N (2021) Curcumin nanoformulations for antimicrobial and wound healing purposes. Phytotherapy Research 35: 2487–2499. https://doi.org/10.1002/ptr.6976
  • Samiei M, Abedi A, Sharifi S, Maleki Dizaj S (2021) Early Osteogenic Differentiation Stimulation of Dental Pulp Stem Cells by Calcitriol and Curcumin. Rodr guez Lozano FJ (Ed.). Stem Cells International 2021: 1–7. https://doi.org/10.1155/2021/9980137
  • Samiei M, Arablouye Moghaddam F, Dalir Abdolahinia E, Ahmadian E, Sharifi S, Maleki Dizaj S (2022) Influence of Curcumin Nanocrystals on the Early Osteogenic Differentiation and Proliferation of Dental Pulp Stem Cells. Prasad R (Ed.). Journal of Nanomaterials 2022: 1–8. https://doi.org/10.1155/2022/8517543
  • Temkin E, Fallach N, Almagor J, Gladstone BP, Tacconelli E, Carmeli Y (2018) Estimating the number of infections caused by antibiotic-resistant Escherichia coli and Klebsiella pneumoniae in 2014: a modelling study. The Lancet Global Health 6: e969–e979. https://doi.org/10.1016/S2214-109X(18)30278-X
  • Udalamaththa VL, Jayasinghe CD, Udagama PV (2016) Potential role of herbal remedies in stem cell therapy: proliferation and differentiation of human mesenchymal stromal cells. Stem Cell Research & Therapy 7: 110. https://doi.org/10.1186/s13287-016-0366-4
  • Yagi H, Chen AF, Hirsch D, Rothenberg AC, Tan J, Alexander PG, Tuan RS (2020) Antimicrobial activity of mesenchymal stem cells against Staphylococcus aureus. Stem Cell Research & Therapy 11: 293. https://doi.org/10.1186/s13287-020-01807-3
login to comment