{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T18:02:28Z","timestamp":1788631348370,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T00:00:00Z","timestamp":1671235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Aydin Adnan Menderes University","award":["ADU-TPF-21043"],"award-info":[{"award-number":["ADU-TPF-21043"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>Organoid models have gained importance in recent years in determining the toxic effects of drugs in cancer studies. Organoid designs with the same standardized size and cellular structures are desired for drug tests. The field of microfluidics offers numerous advantages to enable well-controlled and contamination-free biomedical research. In this study, simple and low-cost microfluidic devices were designed and fabricated to develop an organoid model for drug testing for renal cancers. Caki human renal cancer cells and mesenchymal stem cells isolated from human umbilical cord were placed into alginate hydrogels. The microfluidic system was implemented to form size-controllable organoids within alginate hydrogels. Alginate capsules of uniform sizes formed in the microfluidic system were kept in cell culture for 21 days, and their organoid development was studied with calcein staining. Cisplatin was used as a standard chemotherapeutic, and organoid sphere structures were examined as a function of time with an MTT assay. HIF-1\u03b1, CXCR4 and CXCL-12 chemokine protein, and CXCR4 and CXCL-12 gene levels were tested in organoids and cisplatin responses. In conclusion, it was found that the standard renal cancer organoids made on a lab-on-a-chip system can be used to measure drug effects and tumor microenvironment responses.<\/jats:p>","DOI":"10.3390\/bios12121177","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T04:54:13Z","timestamp":1671425653000},"page":"1177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["On-Chip Organoid Formation to Study CXCR4\/CXCL-12 Chemokine Microenvironment Responses for Renal Cancer Drug Testing"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3124-795X","authenticated-orcid":false,"given":"Adem","family":"Ozcelik","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering, Ayd\u0131n Adnan Menderes University, Aydin 09010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burcin Irem","family":"Abas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Aydin Adnan Menderes University, Aydin 09010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-7077","authenticated-orcid":false,"given":"Omer","family":"Erdogan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Aydin Adnan Menderes University, Aydin 09010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evrim","family":"Cevik","sequence":"additional","affiliation":[{"name":"Department of Machinery and Metal Technologies, Kocarli Vocational School, Aydin Adnan Menderes University, Aydin 09010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9325-3757","authenticated-orcid":false,"given":"Ozge","family":"Cevik","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Aydin Adnan Menderes University, Aydin 09010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1242\/dev.140566","article-title":"Translational applications of adult stem cell-derived organoids","volume":"144","author":"Drost","year":"2017","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1053\/j.gastro.2011.07.050","article-title":"Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett\u2019s epithelium","volume":"141","author":"Sato","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41568-018-0007-6","article-title":"Organoids in cancer research","volume":"18","author":"Drost","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.gde.2013.11.012","article-title":"Organoid cultures for the analysis of cancer phenotypes","volume":"24","author":"Sachs","year":"2014","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/s41467-020-14700-7","article-title":"Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients","volume":"11","author":"Fendler","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/s41467-020-15155-6","article-title":"An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity","volume":"11","author":"Calandrini","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1200\/JCO.2005.04.8280","article-title":"Renal Cell Carcinoma Recurrence After Nephrectomy for Localized Disease: Predicting Survival From Time of Recurrence","volume":"24","author":"Eggener","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"g4797","DOI":"10.1136\/bmj.g4797","article-title":"Renal cell carcinoma","volume":"349","author":"Jonasch","year":"2014","journal-title":"BMJ"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4111","DOI":"10.1038\/s41467-020-17873-3","article-title":"HIF-1\u03b1 and HIF-2\u03b1 differently regulate tumour development and inflammation of clear cell renal cell carcinoma in mice","volume":"11","author":"Hoefflin","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"845401","DOI":"10.3389\/fcell.2022.845401","article-title":"Studying Kidney Diseases Using Organoid Models","volume":"10","author":"Liu","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1517\/14656566.2012.689130","article-title":"Sunitinib malate for the treatment of renal cell carcinoma","volume":"13","author":"Wood","year":"2012","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41419-019-1453-0","article-title":"Organoids as a new model for improving regenerative medicine and cancer personalized therapy in renal diseases","volume":"10","author":"Grassi","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3527","DOI":"10.1681\/ASN.2005050544","article-title":"Nephrogenic Factors Promote Differentiation of Mouse Embryonic Stem Cells into Renal Epithelia","volume":"16","author":"Kim","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.stem.2017.10.011","article-title":"Higher-Order Kidney Organogenesis from Pluripotent Stem Cells","volume":"21","author":"Taguchi","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13045-019-0829-z","article-title":"Applications of patient-derived tumor xenograft models and tumor organoids","volume":"13","author":"Yoshida","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.euf.2019.06.009","article-title":"Tracing Clonal Dynamics Reveals that Two- and Three-dimensional Patient-derived Cell Models Capture Tumor Heterogeneity of Clear Cell Renal Cell Carcinoma","volume":"7","author":"Bolck","year":"2021","journal-title":"Eur. Urol. Focus"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e970","DOI":"10.1002\/ctm2.970","article-title":"Patient-derived renal cell carcinoma organoids for personalized cancer therapy","volume":"12","author":"Li","year":"2022","journal-title":"Clin. Transl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1073\/pnas.1422068112","article-title":"Controlling cell\u2013cell interactions using surface acoustic waves","volume":"112","author":"Guo","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"504006","DOI":"10.1088\/1361-6528\/aae4f1","article-title":"Acoustic assembly of cell spheroids in disposable capillaries","volume":"29","author":"Wu","year":"2018","journal-title":"Nanotechnology"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Regmi, S., Poudel, C., Adhikari, R., and Luo, K.Q. (2022). Applications of Microfluidics and Organ-on-a-Chip in Cancer Research. Biosensors, 12.","DOI":"10.3390\/bios12070459"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41592-019-0325-y","article-title":"Flow-enhanced vascularization and maturation of kidney organoids in vitro","volume":"16","author":"Homan","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1182\/blood-2020-138876","article-title":"Assessment of Red Blood Cell-Mediated Microvascular Occlusion in Sickle Cell Disease By a Novel Electrical Impedance-Based Microfluidic Device","volume":"136","author":"Man","year":"2020","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"954106","DOI":"10.3389\/fphys.2022.954106","article-title":"OcclusionChip: A functional microcapillary occlusion assay complementary to ektacytometry for detection of small-fraction red blood cells with abnormal deformability","volume":"13","author":"Man","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1111\/bjh.18328","article-title":"Antithrombin-III mitigates thrombin-mediated endothelial cell contraction and sickle red blood cell adhesion in microscale flow","volume":"198","author":"Wulftange","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e12662","DOI":"10.1111\/micc.12662","article-title":"Standardized microfluidic assessment of red blood cell\u2013mediated microcapillary occlusion: Association with clinical phenotype and hydroxyurea responsiveness in sickle cell disease","volume":"28","author":"Man","year":"2021","journal-title":"Microcirculation"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bor\u00f3k, A., Laboda, K., and Bony\u00e1r, A. (2021). PDMS Bonding Technologies for Microfluidic Applications: A Review. Biosensors, 11.","DOI":"10.3390\/bios11080292"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1039\/D1LC00030F","article-title":"Tubular human brain organoids to model microglia-mediated neuroinflammation","volume":"21","author":"Ao","year":"2021","journal-title":"Lab Chip"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1039\/D1LC00145K","article-title":"Intelligent acoustofluidics enabled mini-bioreactors for human brain organoids","volume":"21","author":"Cai","year":"2021","journal-title":"Lab Chip"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1039\/D0LC01141J","article-title":"Controllable fusion of human brain organoids using acoustofluidics","volume":"21","author":"Ao","year":"2021","journal-title":"Lab Chip"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2102418","DOI":"10.1002\/advs.202102418","article-title":"Mammary Tumor Organoid Culture in Non-Adhesive Alginate for Luminal Mechanics and High-Throughput Drug Screening","volume":"8","author":"Fang","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Abas, B.I., Demirbolat, G.M., and Cevik, O. (2022). Wharton jelly-derived mesenchymal stem cell exosomes induce apoptosis and suppress EMT signaling in cervical cancer cells as an effective drug carrier system of paclitaxel. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0274607"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113","DOI":"10.30714\/j-ebr.2021267974","article-title":"Alginate encapsulation induce colony formation with umbilical cord-derived mesenchymal stem cells","volume":"4","author":"Abas","year":"2021","journal-title":"Exp. Biomed. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"166","DOI":"10.26701\/ems.769837","article-title":"A Simple Approach for Controlling an Open-Source Syringe Pump","volume":"4","author":"Akkoyun","year":"2020","journal-title":"Eur. Mech. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Galateanu, B., Dimonie, D., Vasile, E., Nae, S., Cimpean, A., and Costache, M. (2012). Layer-shaped alginate hydrogels enhance the biological performance of human adipose-derived stem cells. BMC Biotechnol., 12.","DOI":"10.1186\/1472-6750-12-35"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Duzagac, F., Saorin, G., Memeo, L., Canzonieri, V., and Rizzolio, F. (2021). Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research. Cancers, 13.","DOI":"10.3390\/cancers13040737"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5271","DOI":"10.1038\/s41467-020-19058-4","article-title":"Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids","volume":"11","author":"Schuster","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1002\/ijc.22024","article-title":"Chemokines and cancer","volume":"119","author":"Zlotnik","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s12031-014-0279-6","article-title":"Chemotactic Responses of Neural Stem Cells to SDF-1\u03b1 Correlate Closely with Their Differentiation Status","volume":"54","author":"Chen","year":"2014","journal-title":"J. Mol. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9681698","DOI":"10.1155\/2019\/9681698","article-title":"CXCL12 and Its Isoforms: Different Roles in Pancreatic Cancer?","volume":"2019","author":"Righetti","year":"2019","journal-title":"J. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1084\/jem.20160217","article-title":"High mobility group box 1 orchestrates tissue regeneration via CXCR4","volume":"215","author":"Tirone","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.brainres.2016.06.011","article-title":"SDF-1 and CXCR4 play an important role in adult SVZ lineage cell proliferation and differentiation","volume":"1657","author":"Zhu","year":"2017","journal-title":"Brain Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1158\/0008-5472.465.65.2","article-title":"CXCL12 and vascular endothelial growth factor synergistically induce neoangiogenesis in human ovarian cancers","volume":"65","author":"Kryczek","year":"2005","journal-title":"Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1002\/stem.1407","article-title":"CXC Chemokine Receptor 4 is Essential for Maintenance of Renal cell Carcinoma-Initiating Cells and Predicts Metastasis","volume":"31","author":"Gassenmaier","year":"2013","journal-title":"Stem Cells"}],"container-title":["Biosensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6374\/12\/12\/1177\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:43:13Z","timestamp":1760146993000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6374\/12\/12\/1177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,17]]},"references-count":43,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["bios12121177"],"URL":"https:\/\/doi.org\/10.3390\/bios12121177","relation":{},"ISSN":["2079-6374"],"issn-type":[{"value":"2079-6374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,17]]}}}