{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:41:21Z","timestamp":1790419281554,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Scholarship Council","award":["201908080135"],"award-info":[{"award-number":["201908080135"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mesenchymal stem cells from bone marrow have powerful immunomodulatory capabilities. The interactions between jaw periosteal cells (JPCs) and macrophages are not only relevant for the application of JPCs in regenerative medicine, but this understanding could also help treating diseases like osteonecrosis of the jaw. In previous studies, we analyzed, for the first time, immunomodulatory features of 2D- and 3D-cultured JPCs. In the present work, the effects of JPCs on the polarization state of macrophages in contact coculture were analyzed. To improve the macrophage polarization study, different concentrations of PMA (5 nM, 25 nM, and 150 nM) or different medium supplementations (10% FBS, 10% hPL and 5% hPL) were compared. Further, in order to analyze the effects of JPCs on macrophage polarization, JPCs and PMA-stimulated THP-1 cells were cocultured under LPS\/IFN-\u03b3 or IL-4\/IL-13 stimulatory conditions. Surface marker expression of M1 and M2 macrophages were analyzed under the different culture supplementations in order to investigate the immunomodulatory properties of JPCs. Our results showed that 5 nM PMA can conduct an effective macrophage polarization. The analyses of morphological parameters and surface marker expression showed more distinct M1\/M2 phenotypes over FBS supplementation when using 5% hPL during macrophage polarization. In the coculture, immunomodulatory properties of JPCs improved significantly under 5% hPL supplementation compared to other supplementations. We concluded that, under the culture condition with 5% hPL, JPCs were able to effectively induce THP-1-derived macrophage polarization.<\/jats:p>","DOI":"10.3390\/ijms22094310","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T12:47:07Z","timestamp":1619009227000},"page":"4310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Jaw Periosteum-Derived Mesenchymal Stem Cells Regulate THP-1-Derived Macrophage Polarization"],"prefix":"10.3390","volume":"22","author":[{"given":"Fang","family":"He","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Umrath","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegmar","family":"Reinert","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothea","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1800490","DOI":"10.1002\/adhm.201800490","article-title":"Biomimetic tissue engineering: Tuning the immune and inflammatory response to implantable biomaterials","volume":"7","author":"Taraballi","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1002\/stem.2369","article-title":"Mesenchymal stromal cells induce peculiar alternatively activated macrophages capable of dampening both innate and adaptive immune responses","volume":"34","author":"Chiossone","year":"2016","journal-title":"Stem Cells"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/icb.2012.62","article-title":"Cellular and molecular interactions of mesenchymal stem cells in innate immunity","volume":"91","author":"Moretta","year":"2013","journal-title":"Immunol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/ni.3002","article-title":"Plasticity of mesenchymal stem cells in immunomodulation: Pathological and therapeutic implications","volume":"15","author":"Wang","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Dai, J., Umrath, F., Reinert, S., and Alexander, D. (2020). Jaw Periosteal Cells Seeded in Beta-Tricalcium Phosphate Inhibit Dendritic Cell Maturation. Biomolecules, 10.","DOI":"10.3390\/biom10060887"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dai, J., Rottau, D., Kohler, F., Reinert, S., and Alexander, D. (2018). Effects of jaw periosteal cells on dendritic cell maturation. J. Clin. Med., 7.","DOI":"10.3390\/jcm7100312"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.30579\/mbse.2019.2.1.1","article-title":"M1 and M2 polarization of macrophages: A mini-review","volume":"2","author":"Lee","year":"2019","journal-title":"Med. Biol. Sci. Eng."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1146\/annurev-physiol-022516-034339","article-title":"Macrophage polarization","volume":"79","author":"Murray","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_9","first-page":"263","article-title":"Much more than M1 and M2 macrophages, there are also CD169+ and TCR+ macrophages","volume":"6","author":"Olleros","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sherman, L.S., Cond\u00e9-Green, A., Naaldijk, Y., Lee, E.S., and Rameshwar, P. (2019). An Enzyme-free Method for Isolation and Expansion of Human Adipose-derived Mesenchymal Stem Cells. J. Vis. Exp. JoVE, 16.","DOI":"10.3791\/59419"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"358","DOI":"10.5966\/sctm.2015-0094","article-title":"Xeno-free extraction, culture, and cryopreservation of human adipose-derived mesenchymal stem cells","volume":"5","author":"Escobar","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.tibtech.2019.06.002","article-title":"Production and quality requirements of human platelet lysate: A position statement from the working party on cellular therapies of the international society of blood transfusion","volume":"38","author":"Schallmoser","year":"2020","journal-title":"Trends Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13287-020-01949-4","article-title":"Human platelet lysate as a potential clinical-translatable supplement to support the neurotrophic properties of human adipose-derived stem cells","volume":"11","author":"Palombella","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e1017","DOI":"10.1097\/GOX.0000000000001017","article-title":"Shift toward mechanical isolation of adipose-derived stromal vascular fraction: Review of upcoming techniques","volume":"4","author":"Kotamarti","year":"2016","journal-title":"Plast. Reconstr. Surg. Glob. Open"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.biomaterials.2015.10.065","article-title":"Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation?","volume":"76","author":"Burnouf","year":"2016","journal-title":"Biomaterials"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1007\/s10875-011-9581-z","article-title":"Immunomodulative efficacy of bone marrow-derived mesenchymal stem cells cultured in human platelet lysate","volume":"31","author":"Flemming","year":"2011","journal-title":"J. Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8303959","DOI":"10.1155\/2017\/8303959","article-title":"Platelet lysate: The better choice for jaw periosteal cell mineralization","volume":"2017","author":"Wanner","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1016\/j.vaccine.2018.06.008","article-title":"Ultraviolet-C irradiation for inactivation of viruses in foetal bovine serum","volume":"36","author":"Vaidya","year":"2018","journal-title":"Vaccine"},{"key":"ref_19","first-page":"1","article-title":"Fetal bovine serum (FBS): Past\u2013present\u2013future","volume":"35","author":"Bieback","year":"2018","journal-title":"Altex"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Umrath, F., Steinle, H., Weber, M., Wendel, H.-P., Reinert, S., Alexander, D., and Avci-Adali, M. (2019). Generation of iPSCs from jaw periosteal cells using self-replicating RNA. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071648"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/BF02041244","article-title":"The human leukemia cell line, THP-1: A multifacetted model for the study of monocyte-macrophage differentiation","volume":"47","author":"Auwerx","year":"1991","journal-title":"Experientia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jim.2016.01.012","article-title":"The choice of phorbol 12-myristate 13-acetate differentiation protocol influences the response of THP-1 macrophages to a pro-inflammatory stimulus","volume":"430","author":"Lund","year":"2016","journal-title":"J. Immunol. Methods"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Huang, Y., Tian, C., Li, Q., and Xu, Q. (2019). TET1 knockdown inhibits Porphyromonas gingivalis LPS\/IFN-\u03b3-induced M1 macrophage polarization through the NF-\u03baB pathway in THP-1 cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20082023"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S0171-2985(11)80209-3","article-title":"IL-4 decreases the expression of the monocyte differentiation marker CD14, paralleled by an increasing accessory potency","volume":"182","author":"Ruppert","year":"1991","journal-title":"Immunobiology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1080\/009841098158278","article-title":"Decreased CD11b expression, phagocytosis, and oxidative burst in urban particulate pollution-exposed human monocytes and alveolar macrophages","volume":"55","author":"Becker","year":"1998","journal-title":"J. Toxicol. Environ. Health Part A"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.intimp.2014.08.002","article-title":"THP-1 cell line: An in vitro cell model for immune modulation approach","volume":"23","author":"Chanput","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Danalache, M., Kliesch, S.-M., Munz, M., Naros, A., Reinert, S., and Alexander, D. (2019). Quality Analysis of Minerals Formed by Jaw Periosteal Cells under Different Culture Conditions. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174193"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1651376","DOI":"10.1155\/2017\/1651376","article-title":"Raman spectroscopic analyses of jaw periosteal cell mineralization","volume":"2017","author":"Brauchle","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-40190-9","article-title":"Platelet lysate outperforms FCS and human serum for co-culture of primary human macrophages and hMSCs","volume":"9","author":"Tylek","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.3389\/fimmu.2019.01591","article-title":"Glucocorticoids shape macrophage phenotype for tissue repair","volume":"10","author":"Desgeorges","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_32","first-page":"427","article-title":"Dexamethasone induces aberrant macrophage immune function and apoptosis","volume":"43","author":"Ai","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kim, B.-Y., Son, Y., Lee, J., Choi, J., Kim, C.D., Bae, S.S., Eo, S.-K., and Kim, K. (2017). Dexamethasone inhibits activation of monocytes\/macrophages in a milieu rich in 27-oxygenated cholesterol. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189643"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ohana, Y., Souroujon, M.C., Mittelman, M., and Neumann, D. (2011). Dexamethasone Reduces Viability of Bone Marrow Derived Macrophages, American Society of Hematology.","DOI":"10.1182\/blood.V118.21.4732.4732"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e1009","DOI":"10.1038\/cddis.2013.537","article-title":"The interaction between mesenchymal stem cells and steroids during inflammation","volume":"5","author":"Chen","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nri3073","article-title":"Protective and pathogenic functions of macrophage subsets","volume":"11","author":"Murray","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"eaah5520","DOI":"10.1126\/sciimmunol.aah5520","article-title":"CD169+ macrophages orchestrate innate immune responses by regulating bacterial localization in the spleen","volume":"2","author":"Perez","year":"2017","journal-title":"Sci. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1056\/NEJM198803243181205","article-title":"Monocytes and macrophages","volume":"318","author":"Johnston","year":"1988","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1007\/s00018-014-1796-8","article-title":"Physical and mechanical regulation of macrophage phenotype and function","volume":"72","author":"McWhorter","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17253","DOI":"10.1073\/pnas.1308887110","article-title":"Modulation of macrophage phenotype by cell shape","volume":"110","author":"McWhorter","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4310\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:50:46Z","timestamp":1760161846000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,21]]},"references-count":40,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22094310"],"URL":"https:\/\/doi.org\/10.3390\/ijms22094310","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,21]]}}}