Bioscreening and pre-clinical evaluation of the impact of bioactive molecules from Ptychotis verticillata on the multilineage potential of mesenchymal stromal cells towards immune- and inflammation-mediated diseases.
[en] OBJECTIVE AND DESIGN: Mesenchymal stromal cells (MSCs) are currently used in cell reparative medicine due to their trophic and ant-inflammatory properties. The modulation of stem cell properties by phytochemicals has been suggested as a tool to empower their tissue repair capacity. In vitro, MSCs are characterized by their tri-lineage potential that holds great interest for tissue regeneration. Ptychotis Verticillata (PV), an aromatic and medicinal plant, may be thus used to modulate the in vitro multilineage potential of MSCs.
MATERIALS AND METHODS: We screened the impact of PV-derived essential oil and their bioactive molecules (thymol and carvacrol) on the in vitro multilineage potential of MSCs. Different concentrations and incubation times of these compounds were assessed during the osteogenesis and adipogenesis of MSCs.
RESULTS: The analysis of 75 conditions indicates that these compounds are biologically active by promoting two major differentiation lineages from MSCs. In a time- and dose-dependent manner, thymol and carvacrol increased the osteogenesis and adipogenesis.
CONCLUSION: According to these preliminary observations, the addition of PV extract may stimulate the tissue regenerative and repair functions of MSCs. Further optimization of compound extraction and characterization from PV as well as cell treatment conditions should increase their therapeutic value in combination with MSCs.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Bouhtit, Fatima; Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium ; Genetics and Immune Cell Therapy Unit, Faculty of Sciences, University Mohammed Premier, Oujda, Morocco
Najar, Mehdi ; Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium. mnajar@ulb.ac.be ; Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CRCHUM), Montreal, Canada. mnajar@ulb.ac.be ; Department of Medicine, University of Montreal, Montreal, Canada. mnajar@ulb.ac.be
Rahmani, Saida; Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium ; Genetics and Immune Cell Therapy Unit, Faculty of Sciences, University Mohammed Premier, Oujda, Morocco
Melki, Rahma; Genetics and Immune Cell Therapy Unit, Faculty of Sciences, University Mohammed Premier, Oujda, Morocco
Najimi, Mustapha; Institut de Recherche Expérimentale et Clinique (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Université Catholique de Louvain, Brussels, Belgium
Sadki, Khalid; Laboratory of Human Pathologies Biology, Faculty of Sciences, Mohammed V University Rabat, Agdal, Rabat, Morocco
Boukhatem, Noreddine; Genetics and Immune Cell Therapy Unit, Faculty of Sciences, University Mohammed Premier, Oujda, Morocco
Twizere, Jean-Claude ; Université de Liège - ULiège > TERRA Research Centre > Microbial technologies ; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA
Meuleman, Nathalie; Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Lewalle, Philippe; Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Lagneaux, Laurence; Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
Merimi, Makram; Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium ; Genetics and Immune Cell Therapy Unit, Faculty of Sciences, University Mohammed Premier, Oujda, Morocco
Language :
English
Title :
Bioscreening and pre-clinical evaluation of the impact of bioactive molecules from Ptychotis verticillata on the multilineage potential of mesenchymal stromal cells towards immune- and inflammation-mediated diseases.
Publication date :
August 2022
Journal title :
Inflammation Research
ISSN :
1023-3830
eISSN :
1420-908X
Publisher :
Springer Science and Business Media Deutschland GmbH, Switzerland
Generation Life Foundation F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] Télévie [BE] Les Amis de l’Institut Jules Bordet Research Project
Funding text :
We would like to thank the Cell Therapy Unit team for their helpful discussions and Karlien Pieters for her technical assistance. This study has received support from the Generation Life Foundation, “Fonds National de la Recherche Scientifique (FNRS),” “Télévie,” “Les Amis de l’Institut Jules Bordet”, the Research Project (PDR).
Richardson SM, Hoyland JA, Mobasheri R, Csaki C, Shakibaei M, Mobasheri A. Mesenchymal stem cells in regenerative medicine: opportunities and challenges for articular cartilage and intervertebral disc tissue engineering. J Cell Physiol. 2010;222(1):23–32. 10.1002/jcp.21915. DOI: 10.1002/jcp.21915
Ziani BEC, Barros L, Boumehira AZ, Bachari K, Heleno SA, Alves MJ, et al. Profiling polyphenol composition by HPLC-DAD-ESI/MSn and the antibacterial activity of infusion preparations obtained from four medicinal plants. Food Funct. 2018;9(1):149–59. 10.1039/c7fo01315a. DOI: 10.1039/c7fo01315a
Salehi B, Mishra AP, Shukla I, Sharifi-Rad M, Contreras MDM, Segura-Carretero A, et al. Thymol, thyme, and other plant sources: health and potential uses. Phytother Res. 2018;32(9):1688–706. 10.1002/ptr.6109. DOI: 10.1002/ptr.6109
Najar M, Fayyad-Kazan H, Faour WH, Merimi M, Sokal EM, Lombard CA, et al. Immunological modulation following bone marrow-derived mesenchymal stromal cells and Th17 lymphocyte co-cultures. Inflamm Res. 2019;68(3):203–13. 10.1007/s00011-018-1205-0. DOI: 10.1007/s00011-018-1205-0
Pal B, Das B. In vitro culture of naive human bone marrow mesenchymal stem cells: a stemness based approach. Front Cell Dev Biol. 2017;5:69. 10.3389/fcell.2017.00069. DOI: 10.3389/fcell.2017.00069
Shi Y, Cao J, Wang Y. Rethinking regeneration: empowerment of stem cells by inflammation. Cell Death Differ. 2015;22(12):1891–2. 10.1038/cdd.2015.127. DOI: 10.1038/cdd.2015.127
Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014;15(11):1009–16. 10.1038/ni.3002. DOI: 10.1038/ni.3002
Krampera M. Mesenchymal stromal cell ‘licensing’: a multistep process. Leukemia. 2011;25(9):1408–14. 10.1038/leu.2011.108. DOI: 10.1038/leu.2011.108
Najar M, Bouhtit F, Melki R, Afif H, Hamal A, Fahmi H, et al. Mesenchymal stromal cell-based therapy: new perspectives and challenges. J Clin Med. 2019. 10.3390/jcm8050626. DOI: 10.3390/jcm8050626
Jiang D, Scharffetter-Kochanek K. Mesenchymal stem cells adaptively respond to environmental cues thereby improving granulation tissue formation and wound healing. Front Cell Dev Biol. 2020;8:697. 10.3389/fcell.2020.00697. DOI: 10.3389/fcell.2020.00697
Planat-Benard V, Varin A, Casteilla L. MSCs and inflammatory cells crosstalk in regenerative medicine: concerted actions for optimized resolution driven by energy metabolism. Front Immunol. 2021;12: 626755. 10.3389/fimmu.2021.626755. DOI: 10.3389/fimmu.2021.626755
Klimczak A, Kozlowska U. Mesenchymal stromal cells and tissue-specific progenitor cells: their role in tissue homeostasis. Stem Cells Int. 2016;2016:4285215. 10.1155/2016/4285215. DOI: 10.1155/2016/4285215
Shao J, Zhang W, Yang T. Using mesenchymal stem cells as a therapy for bone regeneration and repairing. Biol Res. 2015;48:62. 10.1186/s40659-015-0053-4. DOI: 10.1186/s40659-015-0053-4
el Ouariachi ME, Tomi P, Bouyanzer A, Hammouti B, Desjobert JM, Costa J, et al. Chemical composition and antioxidant activity of essential oils and solvent extracts of Ptychotis verticillata from Morocco. Food Chem Toxicol. 2011;49(2):533–6. 10.1016/j.fct.2010.11.019. DOI: 10.1016/j.fct.2010.11.019
Spisni E, Petrocelli G, Imbesi V, Spigarelli R, Azzinnari D, Donati Sarti M, et al. Antioxidant, anti-inflammatory, and microbial-modulating activities of essential oils: implications in colonic pathophysiology. Int J Mol Sci. 2020. 10.3390/ijms21114152. DOI: 10.3390/ijms21114152
Najar M, Merimi M, Faour WH, Lombard CA, Moussa Agha D, Ouhaddi Y, et al. In vitro cellular and molecular interplay between human foreskin-derived mesenchymal stromal/stem cells and the Th17 cell pathway. Pharmaceutics. 2021. 10.3390/pharmaceutics13101736. DOI: 10.3390/pharmaceutics13101736
Chen Q, Shou P, Zheng C, Jiang M, Cao G, Yang Q, et al. Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? Cell Death Differ. 2016;23(7):1128–39. 10.1038/cdd.2015.168. DOI: 10.1038/cdd.2015.168
Kim N, Cho SG. Overcoming immunoregulatory plasticity of mesenchymal stem cells for accelerated clinical applications. Int J Hematol. 2016;103(2):129–37. 10.1007/s12185-015-1918-6. DOI: 10.1007/s12185-015-1918-6
Naji A, Eitoku M, Favier B, Deschaseaux F, Rouas-Freiss N, Suganuma N. Biological functions of mesenchymal stem cells and clinical implications. Cell Mol Life Sci. 2019;76(17):3323–48. 10.1007/s00018-019-03125-1. DOI: 10.1007/s00018-019-03125-1
Udalamaththa VL, Jayasinghe CD, Udagama PV. Potential role of herbal remedies in stem cell therapy: proliferation and differentiation of human mesenchymal stromal cells. Stem Cell Res Ther. 2016;7(1):110. 10.1186/s13287-016-0366-4. DOI: 10.1186/s13287-016-0366-4
Xue W, Yu J, Chen W. Plants and their bioactive constituents in mesenchymal stem cell-based periodontal regeneration: a novel prospective. Biomed Res Int. 2018;2018:7571363. 10.1155/2018/7571363. DOI: 10.1155/2018/7571363
Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol. 2014;32(3):252–60. 10.1038/nbt.2816. DOI: 10.1038/nbt.2816
Smith JR, Pochampally R, Perry A, Hsu SC, Prockop DJ. Isolation of a highly clonogenic and multipotential subfraction of adult stem cells from bone marrow stroma. Stem Cells. 2004;22(5):823–31. 10.1634/stemcells.22-5-823. DOI: 10.1634/stemcells.22-5-823
Austgulen LT, Solheim E, Scheline RR. Metabolism in rats of p-cymene derivatives: carvacrol and thymol. Pharmacol Toxicol. 1987;61(2):98–102. 10.1111/j.1600-0773.1987.tb01783.x. DOI: 10.1111/j.1600-0773.1987.tb01783.x
Mason SE, Mullen KAE, Anderson KL, Washburn SP, Yeatts JL, Baynes RE. Pharmacokinetic analysis of thymol, carvacrol and diallyl disulfide after intramammary and topical applications in healthy organic dairy cattle. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2017;34(5):740–9. 10.1080/19440049.2017.1285056. DOI: 10.1080/19440049.2017.1285056
Qin Y, Guan J, Zhang C. Mesenchymal stem cells: mechanisms and role in bone regeneration. Postgrad Med J. 2014;90(1069):643–7. 10.1136/postgradmedj-2013-132387. DOI: 10.1136/postgradmedj-2013-132387
Knight MN, Hankenson KD. Mesenchymal stem cells in bone regeneration. Adv Wound Care (New Rochelle). 2013;2(6):306–16. 10.1089/wound.2012.0420. DOI: 10.1089/wound.2012.0420
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–7. 10.1126/science.284.5411.143. DOI: 10.1126/science.284.5411.143
Li H, Shen S, Fu H, Wang Z, Li X, Sui X, et al. Immunomodulatory functions of mesenchymal stem cells in tissue engineering. Stem Cells Int. 2019;2019:9671206. 10.1155/2019/9671206. DOI: 10.1155/2019/9671206
Li G, Zhang XA, Zhang JF, Chan CY, Yew DT, He ML, et al. Ethanol extract of Fructus Ligustri Lucidi promotes osteogenesis of mesenchymal stem cells. Phytother Res. 2010;24(4):571–6. 10.1002/ptr.2987. DOI: 10.1002/ptr.2987
Yamada Y, Ueda M, Naiki T, Nagasaka T. Tissue-engineered injectable bone regeneration for osseointegrated dental implants. Clin Oral Implants Res. 2004;15(5):589–97. 10.1111/j.1600-0501.2004.01038.x. DOI: 10.1111/j.1600-0501.2004.01038.x
Tseng SS, Lee MA, Reddi AH. Nonunions and the potential of stem cells in fracture-healing. J Bone Joint Surg Am. 2008;90(Suppl 1):92–8. 10.2106/JBJS.G.01192. DOI: 10.2106/JBJS.G.01192
Mollazadeh S, Neshati V, Fazly Bazzaz BS, Iranshahi M, Mojarrad M, Naderi-Meshkin H, et al. Standardized Sophora pachycarpa root extract enhances osteogenic differentiation in adipose-derived human mesenchymal stem cells. Phytother Res. 2017;31(5):792–800. 10.1002/ptr.5803. DOI: 10.1002/ptr.5803
Chen X, Yan L, Guo Z, Chen Z, Chen Y, Li M, et al. Adipose-derived mesenchymal stem cells promote the survival of fat grafts via crosstalk between the Nrf2 and TLR4 pathways. Cell Death Dis. 2016;7(9): e2369. 10.1038/cddis.2016.261. DOI: 10.1038/cddis.2016.261
Costa MF, Durco AO, Rabelo TK, Barreto RSS, Guimaraes AG. Effects of carvacrol, thymol and essential oils containing such monoterpenes on wound healing: a systematic review. J Pharm Pharmacol. 2019;71(2):141–55. 10.1111/jphp.13054. DOI: 10.1111/jphp.13054
Nagoor Meeran MF, Javed H, Al Taee H, Azimullah S, Ojha SK. Pharmacological properties and molecular mechanisms of thymol: prospects for its therapeutic potential and pharmaceutical development. Front Pharmacol. 2017;8:380. 10.3389/fphar.2017.00380. DOI: 10.3389/fphar.2017.00380
Parkatzidis K, Chatzinikolaidou M, Koufakis E, Kaliva M, Farsaria M, Vamvakaki M. Multi-photon polymerization of bio-inspired, thymol-functionalized hybrid materials with biocompatible and antimicrobial activity. Polym Chem. 2020;11(25):4078–83. 10.1039/D0PY00281J. DOI: 10.1039/D0PY00281J
Beederman M, Lamplot JD, Nan G, Wang J, Liu X, Yin L, et al. BMP signaling in mesenchymal stem cell differentiation and bone formation. J Biomed Sci Eng. 2013;6(8A):32–52. 10.4236/jbise.2013.68A1004. DOI: 10.4236/jbise.2013.68A1004
Brito FN, Vendramin FS, Lopes CTA, Costa MPR, Ohashi OM, Maia JGS, et al. Proliferation of human adipose tissue-derived stem cells stimulated by oil rich in thymol of Lippia origanoides. Acta Cir Bras. 2018;33(5):431–8. 10.1590/s0102-865020180050000005. DOI: 10.1590/s0102-865020180050000005
Zielinska-Blajet M, Pietrusiak P, Feder-Kubis J. Selected monocyclic monoterpenes and their derivatives as effective anticancer therapeutic agents. Int J Mol Sci. 2021. 10.3390/ijms22094763. DOI: 10.3390/ijms22094763
Matluobi D, Araghi A, Maragheh BFA, Rezabakhsh A, Soltani S, Khaksar M, et al. Carvacrol promotes angiogenic paracrine potential and endothelial differentiation of human mesenchymal stem cells at low concentrations. Microvasc Res. 2018;115:20–7. 10.1016/j.mvr.2017.08.003. DOI: 10.1016/j.mvr.2017.08.003
Hotta M, Nakata R, Katsukawa M, Hori K, Takahashi S, Inoue H. Carvacrol, a component of thyme oil, activates PPARalpha and gamma and suppresses COX-2 expression. J Lipid Res. 2010;51(1):132–9. 10.1194/jlr.M900255-JLR200. DOI: 10.1194/jlr.M900255-JLR200
Yuan SM, Guo Y, Wang Q, Xu Y, Wang M, Chen HN, et al. Over-expression of PPAR-gamma2 gene enhances the adipogenic differentiation of hemangioma-derived mesenchymal stem cells in vitro and in vivo. Oncotarget. 2017;8(70):115817–28. 10.1863/oncotarget.23705. DOI: 10.1863/oncotarget.23705
Bruedigam C, Eijken M, Koedam M, van de Peppel J, Drabek K, Chiba H, et al. A new concept underlying stem cell lineage skewing that explains the detrimental effects of thiazolidinediones on bone. Stem Cells. 2010;28(5):916–27. 10.1002/stem.405. DOI: 10.1002/stem.405
Wang N, Wang L, Wang Z, Cheng L, Wang J. Solanum muricatum ameliorates the symptoms of osteogenesis imperfecta in vivo. J Food Sci. 2019;84(6):1646–50. 10.1111/1750-3841.14637. DOI: 10.1111/1750-3841.14637
Bouhtit F, Najar M, Agha DM, Melki R, Najimi M, Sadki K, et al. The biological response of mesenchymal stromal cells to thymol and carvacrol in comparison to their essential oil: an innovative new study. Food Chem Toxicol. 2019;134: 110844. 10.1016/j.fct.2019.110844. DOI: 10.1016/j.fct.2019.110844
Gholijani N, Gharagozloo M, Farjadian S, Amirghofran Z. Modulatory effects of thymol and carvacrol on inflammatory transcription factors in lipopolysaccharide-treated macrophages. J Immunotoxicol. 2016;13(2):157–64. 10.3109/1547691X.2015.1029145. DOI: 10.3109/1547691X.2015.1029145
Liu SD, Song MH, Yun W, Lee JH, Kim HB, Cho JH. Effect of carvacrol essential oils on immune response and inflammation-related genes expression in broilers challenged by lipopolysaccharide. Poult Sci. 2019;98(5):2026–33. 10.3382/ps/pey575. DOI: 10.3382/ps/pey575
