{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:54:18Z","timestamp":1790916858311,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Mast cells are highly granulated tissue-resident leukocytes that require a three-dimensional matrix to differentiate and mediate immune responses. However, almost all cultured mast cells rely on two-dimensional suspension or adherent cell culture systems, which do not adequately reflect the complex structure that these cells require for optimal function.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Crystalline nanocellulose (CNC), consisting of rod-like crystals 4\u201315\u00a0nm in diameter and 0.2\u20131\u00a0\u00b5m in length, were dispersed in an agarose matrix (12.5% w\/v), and bone marrow derived mouse mast cells (BMMC) were cultured on the agarose\/CNC composite. BMMC were activated with the calcium ionophore A23187 or immunoglobulin E (IgE) and antigen (Ag) to crosslink high affinity IgE receptors (Fc\u03b5RI).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> BMMC cultured on a CNC\/agarose matrix remained viable and metabolically active as measured by reduction of sodium 3\u2032-[1-[(phenylamino)-carbony]-3,4-tetrazolium]-bis(4-methoxy-6-nitro) benzene-sulfonic acid hydrate (XTT), and the cells maintained their membrane integrity as analyzed by measuring the release of lactate dehydrogenase (LDH) and propidium iodide exclusion by flow cytometry. Culture on CNC\/agarose matrix had no effect on BMMC degranulation in response to IgE\/Ag or A23187. However, culture of BMMC on a CNC\/agarose matrix inhibited A23187-and IgE\/Ag-activated production of tumor necrosis factor (TNF) and other mediators such as IL-1\u03b2, IL-4, IL-6, IL-13, MCP-1\/CCL2, MMP-9 and RANTES by as much as 95%. RNAseq analysis indicated that BMMC expressed a unique and balanced transcriptome when cultured on CNC\/agarose.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> These data demonstrate that culture of BMMCs on a CNC\/agarose matrix promotes cell integrity, maintains expression of surface biomarkers such as Fc\u03b5RI and KIT and preserves the ability of BMMC to release pre-stored mediators in response to IgE\/Ag and A23187. However, culture of BMMC on CNC\/agarose matrix inhibits BMMC production of <jats:italic>de novo<\/jats:italic> synthesized mediators, suggesting that CNC may be altering specific phenotypic characteristics of these cells that are associated with late phase inflammatory responses.<\/jats:p>","DOI":"10.3389\/fbioe.2023.1160460","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T06:02:47Z","timestamp":1681192967000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Agarose\/crystalline nanocellulose (CNC) composites promote bone marrow-derived mast cell integrity, degranulation and receptor expression but inhibit production of de novo synthesized mediators"],"prefix":"10.3389","volume":"11","author":[{"given":"Marianna","family":"Kulka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Young","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Benazir","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy Ramielle","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Jovel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leshern","family":"Karamchand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Marcet-Palacios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2419","DOI":"10.1021\/acs.biomac.1c00228","article-title":"Multifunctional gold nanoparticle-conjugated cellulose nanoonions alleviate A\u03b242 fibrillation-induced toxicity via regulation of oxidative stress and ion homeostasis","volume":"22","author":"Abidi","year":"2021","journal-title":"Biomacromolecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.cbi.2018.02.015","article-title":"Renal toxicological evaluations of sulphonated nanocellulose from khaya sengalensis seed in wistar rats","volume":"284","author":"Adewuyi","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"B3","doi-asserted-by":"publisher","first-page":"6704","DOI":"10.3390\/molecules27196704","article-title":"Quercetin and resveratrol differentially decrease expression of the high-affinity IgE receptor (Fc\u03b5RI) by human and mouse mast cells","volume":"27","author":"Alam","year":"2022","journal-title":"Molecules"},{"key":"B4","doi-asserted-by":"publisher","first-page":"8261","DOI":"10.1080\/07391102.2021.1910569","article-title":"Docking and molecular dynamics predicted B-DNA and dihydropyrimidinone selenoesters interactions elucidating antiproliferative effects on breast adenocarcinoma cells","volume":"40","author":"Benassi","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"B5","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1159\/000234197","article-title":"The role of mast cells in inflammatory processes: Evidence for nerve\/mast cell interactions","volume":"82","author":"Bienenstock","year":"1987","journal-title":"Int. Arch. Allergy Appl. Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3792","DOI":"10.1021\/acsami.1c21039","article-title":"Development of cellulose nanofibril\/casein-based 3d composite hemostasis scaffold for potential wound-healing application","volume":"14","author":"Biranje","year":"2022","journal-title":"ACS Appl. Mater Interfaces"},{"key":"B7","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1038\/nbt0816-888d","article-title":"Erratum: Near-Optimal probabilistic rna-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic rna-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"968458","DOI":"10.3389\/fmolb.2022.968458","article-title":"Ptbps: An immunomodulatory-related prognostic biomarker in pan-cancer","volume":"9","author":"Chen","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1210\/me.2014-1406","article-title":"Genome-wide mapping and interrogation of the Nmp4 antianabolic bone Axis","volume":"29","author":"Childress","year":"2015","journal-title":"Mol. Endocrinol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e202006085","DOI":"10.1083\/jcb.202006085","article-title":"Centriole and pcm cooperatively recruit Cep192 to spindle Poles to promote bipolar spindle assembly","volume":"220","author":"Chinen","year":"2021","journal-title":"J. Cell Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1039\/c9en00184k","article-title":"Toxicological effects of ingested nanocellulose in in vitro intestinal epithelium and in vivo rat models","volume":"6","author":"DeLoid","year":"2019","journal-title":"Environ. Sci. Nano"},{"key":"B13","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1182\/blood.v61.4.775.bloodjournal614775","article-title":"Basophil\/mast cell precursors in human peripheral blood","volume":"61","author":"Denburg","year":"1983","journal-title":"Blood"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1080\/15384101.2022.2052530","article-title":"Ptbp3 mediates tgf-beta-induced emt and metastasis of lung adenocarcinoma","volume":"21","author":"Dong","year":"2022","journal-title":"Cell Cycle"},{"key":"B15","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12951-016-0230-9","article-title":"A critical review of the current knowledge regarding the biological impact of nanocellulose","volume":"14","author":"Endes","year":"2016","journal-title":"J. Nanobiotechnology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.3390\/life12091427","article-title":"Curcumin modulates oxidative stress, fibrosis, and apoptosis in drug-resistant cancer cell lines","volume":"12","author":"Gabr","year":"2022","journal-title":"Life (Basel)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"D33","DOI":"10.1093\/nar\/gky822","article-title":"Animaltfdb 3.0: A comprehensive resource for annotation and prediction of animal transcription factors","volume":"47","author":"Hu","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/978-1-0716-2557-6_12","article-title":"Assessment of hepatocyte ploidy by flow cytometry","volume":"2544","author":"Jin","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3791\/62519","article-title":"Fabrication of a crystalline nanocellulose embedded agarose biomaterial ink for bone marrow-derived mast cell culture","volume":"171","author":"Karamchand","year":"2021","journal-title":"J. Vis. Exp."},{"key":"B20","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1263\/jbb.103.389","article-title":"Methods for inducing embryoid body formation: In vitro differentiation system of embryonic stem cells","volume":"103","author":"Kurosawa","year":"2007","journal-title":"J. Biosci. Bioeng."},{"key":"B21","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for rna-seq data with Deseq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1002\/jbm.a.37267","article-title":"Incorporating nanocrystalline cellulose into a multifunctional hydrogel for heart valve tissue engineering applications","volume":"110","author":"Ma","year":"2022","journal-title":"J. Biomed. Mater Res. A"},{"key":"B23","doi-asserted-by":"publisher","first-page":"7064","DOI":"10.1038\/s41467-022-34906-1","article-title":"A myb enhancer-guided analysis of basophil and mast cell differentiation","volume":"13","author":"Matsumura","year":"2022","journal-title":"Nat. Commun."},{"key":"B24","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.chemosphere.2016.12.105","article-title":"Fibrillar vs crystalline nanocellulose pulmonary epithelial cell responses: Cytotoxicity or inflammation?","volume":"171","author":"Menas","year":"2017","journal-title":"Chemosphere"},{"key":"B25","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1002\/jat.4390","article-title":"Potential issues specific to cytotoxicity tests of cellulose nanofibrils","volume":"43","author":"Moriyama","year":"2022","journal-title":"J. Appl. Toxicol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"113204","DOI":"10.1016\/j.fct.2022.113204","article-title":"Investigation of eight cellulose nanomaterials' impact on differentiated caco-2 monolayer integrity and cytotoxicity","volume":"166","author":"Mortensen","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1182\/blood.v60.2.352.bloodjournal602352","article-title":"Clonal assay of mouse mast cell colonies in methylcellulose culture","volume":"60","author":"Nakahata","year":"1982","journal-title":"Blood"},{"key":"B28","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1002\/jcb.25382","article-title":"Mice deficient in ciz\/nmp4 develop an attenuated form of K\/Bxn-Serum induced arthritis","volume":"117","author":"Nakamoto","year":"2016","journal-title":"J. Cell Biochem."},{"key":"B29","first-page":"35","article-title":"Differentiation and proliferative kinetics of hemopoietic stem cells in culture","volume":"148","author":"Ogawa","year":"1984","journal-title":"Prog. Clin. Biol. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"64","DOI":"10.3390\/jfb12040064","article-title":"Functionalized nanocellulose drives neural stem cells toward neuronal differentiation","volume":"12","author":"Pandanaboina","year":"2021","journal-title":"J. Funct. Biomater."},{"key":"B31","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1089\/dna.2015.3110","article-title":"The transcription factor Nmp4 binds to the Aqp5 promoter and is a novel transcriptional regulator of the Aqp5 gene","volume":"35","author":"Rump","year":"2016","journal-title":"DNA Cell Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"10421","DOI":"10.1002\/jcp.27710","article-title":"Thymoquinone-induced antitumor and apoptosis in human lung adenocarcinoma cells","volume":"234","author":"Samarghandian","year":"2019","journal-title":"J. Cell Physiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbrep.2015.08.008","article-title":"Cellulose nanocrystal cationic derivative induces NLRP3 inflammasome-dependent IL-1\u03b2 secretion associated with mitochondrial ROS production","volume":"4","author":"Sunasee","year":"2015","journal-title":"Biochem. Biophys. Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.3390\/biom11111588","article-title":"Heat shock proteins Hspa1 and Hsp90aa1 are upregulated in colorectal polyps and can Be targeted in cancer cells by anti-inflammatory oxicams with arylpiperazine pharmacophore and benzoyl moiety substitutions at thiazine ring","volume":"11","author":"Szczuka","year":"2021","journal-title":"Biomolecules"},{"key":"B35","doi-asserted-by":"publisher","first-page":"16153","DOI":"10.1074\/jbc.M107496200","article-title":"DNA binding and gene activation properties of the Nmp4 nuclear matrix transcription factors","volume":"277","author":"Torrungruang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2322","DOI":"10.3390\/nano11092322","article-title":"Bacterial nanocellulose as a scaffold for in vitro cell migration assay","volume":"11","author":"Ugrin","year":"2021","journal-title":"Nanomater. (Basel)"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1016\/j.hrthm.2021.06.1194","article-title":"Atrial heat shock protein levels are associated with early postoperative and persistence of atrial fibrillation","volume":"18","author":"van Marion","year":"2021","journal-title":"Heart"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e1901642","DOI":"10.1002\/smll.201901642","article-title":"The crystallinity and aspect ratio of cellulose nanomaterials determine their pro-inflammatory and immune adjuvant effects in vitro and in vivo","volume":"15","author":"Wang","year":"2019","journal-title":"Small"},{"key":"B39","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.molimm.2012.01.009","article-title":"Tumor-mast cell interactions: Induction of pro-tumorigenic genes and anti-tumorigenic 4-1bb in mcs in response to Lewis lung carcinoma","volume":"50","author":"Wensman","year":"2012","journal-title":"Mol. Immunol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/s41419-022-04564-8","article-title":"Ptbp3 modulates P53 expression and promotes colorectal cancer cell proliferation by maintaining Ube4a mrna stability","volume":"13","author":"Xie","year":"2022","journal-title":"Cell Death Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/s41385-020-0280-z","article-title":"Nmp4 regulates the innate immune response to influenza a virus infection","volume":"14","author":"Yang","year":"2021","journal-title":"Mucosal Immunol."}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2023.1160460\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T06:02:51Z","timestamp":1681192971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2023.1160460\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,11]]},"references-count":41,"alternative-id":["10.3389\/fbioe.2023.1160460"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2023.1160460","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,11]]},"article-number":"1160460"}}