{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T04:37:13Z","timestamp":1771907833084,"version":"3.50.1"},"reference-count":194,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","doi-asserted-by":"publisher","award":["PTDC\/MED-ONC\/1215\/2021\/PT"],"award-info":[{"award-number":["PTDC\/MED-ONC\/1215\/2021\/PT"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite the wide variety of existing therapies, multiple myeloma (MM) remains a disease with dismal prognosis. Choosing the right treatment for each patient remains one of the major challenges. A new approach being explored is the use of ex vivo models for personalized medicine. Two-dimensional culture or animal models often fail to predict clinical outcomes. Three-dimensional ex vivo models using patients\u2019 bone marrow (BM) cells may better reproduce the complexity and heterogeneity of the BM microenvironment. Here, we review the strengths and limitations of currently existing patient-derived ex vivo three-dimensional MM models. We analyze their biochemical and biophysical properties, molecular and cellular characteristics, as well as their potential for drug testing and identification of disease biomarkers. Furthermore, we discuss the remaining challenges and give some insight on how to achieve a more biomimetic and accurate MM BM model. Overall, there is still a need for standardized culture methods and refined readout techniques. Including both myeloma and other cells of the BM microenvironment in a simple and reproducible three-dimensional scaffold is the key to faithfully mapping and examining the relationship between these players in MM. This will allow a patient-personalized profile, providing a powerful tool for clinical and research applications.<\/jats:p>","DOI":"10.3390\/ijms232112888","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T22:00:27Z","timestamp":1666735227000},"page":"12888","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Patient-Derived Multiple Myeloma 3D Models for Personalized Medicine\u2014Are We There Yet?"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9761-1398","authenticated-orcid":false,"given":"Diana","family":"Louren\u00e7o","sequence":"first","affiliation":[{"name":"Myeloma Lymphoma Research Group\u2014Champalimaud Experimental Clinical Research Programme of Champalimaud Foundation, 1400-038 Lisbon, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2378-6192","authenticated-orcid":false,"given":"Raquel","family":"Lopes","sequence":"additional","affiliation":[{"name":"Myeloma Lymphoma Research Group\u2014Champalimaud Experimental Clinical Research Programme of Champalimaud Foundation, 1400-038 Lisbon, Portugal"},{"name":"Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8421-6965","authenticated-orcid":false,"given":"Carolina","family":"Pestana","sequence":"additional","affiliation":[{"name":"Myeloma Lymphoma Research Group\u2014Champalimaud Experimental Clinical Research Programme of Champalimaud Foundation, 1400-038 Lisbon, Portugal"},{"name":"Centre of Statistics and Its Applications, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal"}]},{"given":"Ana C.","family":"Queir\u00f3s","sequence":"additional","affiliation":[{"name":"Myeloma Lymphoma Research Group\u2014Champalimaud Experimental Clinical Research Programme of Champalimaud Foundation, 1400-038 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3978-766X","authenticated-orcid":false,"given":"Cristina","family":"Jo\u00e3o","sequence":"additional","affiliation":[{"name":"Myeloma Lymphoma Research Group\u2014Champalimaud Experimental Clinical Research Programme of Champalimaud Foundation, 1400-038 Lisbon, Portugal"},{"name":"Faculty of Medical Sciences, NOVA Medical School, 1169-056 Lisbon, Portugal"},{"name":"Hemato-Oncology Department of Champalimaud Foundation, 1400-038 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5235-6557","authenticated-orcid":false,"given":"Emilie Arnault","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Myeloma Lymphoma Research Group\u2014Champalimaud Experimental Clinical Research Programme of Champalimaud Foundation, 1400-038 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA. Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e538","DOI":"10.1016\/S1470-2045(14)70442-5","article-title":"International Myeloma Working Group Updated Criteria for the Diagnosis of Multiple Myeloma","volume":"15","author":"Rajkumar","year":"2014","journal-title":"Lancet. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1056\/NEJMra1011442","article-title":"Multiple Myeloma","volume":"364","author":"Palumbo","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.2217\/fon-2016-0057","article-title":"3D Tissue-Engineered Bone Marrow: What Does This Mean for the Treatment of Multiple Myeloma?","volume":"12","author":"Azab","year":"2016","journal-title":"Future Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"157496","DOI":"10.1155\/2012\/157496","article-title":"Bone Marrow Microenvironment in Multiple Myeloma Progression","volume":"2012","author":"Manier","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"198539","DOI":"10.1155\/2014\/198539","article-title":"Immunological Dysregulation in Multiple Myeloma Microenvironment","volume":"2014","author":"Romano","year":"2014","journal-title":"Biomed Res. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccr.2012.02.022","article-title":"Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment","volume":"21","author":"Hanahan","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Papadimitriou, K., Kostopoulos, I.V., Tsopanidou, A., Orologas-Stavrou, N., Kastritis, E., Tsitsilonis, O., Dimopoulos, M.A., and Terpos, E. (2020). Ex Vivo Models Simulating the Bone Marrow Environment and Predicting Response to Therapy in Multiple Myeloma. Cancers, 12.","DOI":"10.3390\/cancers12082006"},{"key":"ref_9","first-page":"40","article-title":"Bioengineering 3D Environments for Cancer Models","volume":"79","author":"Semino","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1093\/jnci\/djr218","article-title":"Randomized Phase II Trials: A Long-Term Investment with Promising Returns","volume":"103","author":"Sharma","year":"2011","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1053\/j.seminoncol.2016.11.004","article-title":"Multiple Myeloma Epidemiology and Survival: A Unique Malignancy","volume":"43","author":"Kazandjian","year":"2016","journal-title":"Semin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nri3311","article-title":"Humanized Mice for Immune System Investigation: Progress, Promise and Challenges","volume":"12","author":"Shultz","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s13045-019-0832-4","article-title":"Emerging Organoid Models: Leaping Forward in Cancer Research","volume":"12","author":"Fan","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vinci, M., Gowan, S., Boxall, F., Patterson, L., Zimmermann, M., Court, W., Lomas, C., Mendiola, M., Hardisson, D., and Eccles, S.A. (2012). Advances in Establishment and Analysis of Three-Dimensional Tumor Spheroid-Based Functional Assays for Target Validation and Drug Evaluation. BMC Biol., 10.","DOI":"10.1186\/1741-7007-10-29"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/S0140-6736(21)00135-5","article-title":"Multiple Myeloma","volume":"397","author":"Pawlyn","year":"2021","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1200\/JCO.2015.61.2267","article-title":"Revised International Staging System for Multiple Myeloma: A Report from International Myeloma Working Group","volume":"33","author":"Palumbo","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nrclinonc.2017.166","article-title":"Tumour Heterogeneity and Resistance to Cancer Therapies","volume":"15","author":"Shaw","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature12627","article-title":"Tumour Heterogeneity in the Clinic","volume":"501","author":"Bedard","year":"2013","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"jcs201707","DOI":"10.1242\/jcs.201707","article-title":"The Bone Marrow Microenvironment in Health and Disease at a Glance","volume":"131","author":"Kumar","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"345","DOI":"10.2174\/138920109787847493","article-title":"Multiple Myeloma Bone Marrow Niche","volume":"10","author":"Basak","year":"2009","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lopes, R., Caetano, J., Ferreira, B., Barahona, F., Carneiro, E.A., and Jo\u00e3o, C. (2021). The Immune Microenvironment in Multiple Myeloma: Friend or Foe?. Cancers, 13.","DOI":"10.3390\/cancers13040625"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/imr.12233","article-title":"Targeting the Bone Marrow Microenvironment in Multiple Myeloma","volume":"263","author":"Kawano","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e547","DOI":"10.1038\/bcj.2017.24","article-title":"Regulatory B Cell-Myeloma Cell Interaction Confers Immunosuppression and Promotes Their Survival in the Bone Marrow Milieu","volume":"7","author":"Zhang","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1038\/leu.2015.79","article-title":"PD-L1\/PD-1 Presence in the Tumor Microenvironment and Activity of PD-1 Blockade in Multiple Myeloma","volume":"29","author":"Paiva","year":"2015","journal-title":"Leukemia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1038\/leu.2015.11","article-title":"Targeting PD1-PDL1 Immune Checkpoint in Plasmacytoid Dendritic Cell Interactions with T Cells, Natural Killer Cells and Multiple Myeloma Cells","volume":"29","author":"Ray","year":"2015","journal-title":"Leukemia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.7150\/jca.30102","article-title":"High Numbers of CD163+ Tumor-Associated Macrophages Correlate with Poor Prognosis in Multiple Myeloma Patients Receiving Bortezomib-Based Regimens","volume":"10","author":"Wang","year":"2019","journal-title":"J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/s41419-019-2012-4","article-title":"CCL2 Promotes Macrophages-Associated Chemoresistance via MCPIP1 Dual Catalytic Activities in Multiple Myeloma","volume":"10","author":"Xu","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1182\/blood-2007-10-116129","article-title":"Improved Survival in Multiple Myeloma and the Impact of Novel Therapies","volume":"111","author":"Kumar","year":"2008","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lopes, R., Ferreira, B.V., Caetano, J., Barahona, F., Carneiro, E.A., and Jo\u00e3o, C. (2021). Boosting Immunity against Multiple Myeloma. Cancers, 13.","DOI":"10.3390\/cancers13061221"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5959","DOI":"10.1158\/1078-0432.CCR-16-0184","article-title":"New Strategies in Multiple Myeloma: Immunotherapy as a Novel Approach to Treat Patients with Multiple Myeloma","volume":"22","author":"Neri","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Charli\u0144ski, G., Vesole, D.H., and Jurczyszyn, A. (2021). Rapid Progress in the Use of Immunomodulatory Drugs and Cereblon E3 Ligase Modulators in the Treatment of Multiple Myeloma. Cancers, 13.","DOI":"10.3390\/cancers13184666"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/leu.2011.381","article-title":"Increased Osteocyte Death in Multiple Myeloma Patients: Role in Myeloma-Induced Osteoclast Formation","volume":"26","author":"Giuliani","year":"2012","journal-title":"Leukemia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1158\/0008-5472.CAN-15-1703","article-title":"Bidirectional Notch Signaling and Osteocyte-Derived Factors in the Bone Marrow Microenvironment Promote Tumor Cell Proliferation and Bone Destruction in Multiple Myeloma","volume":"76","author":"Anderson","year":"2016","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41408-017-0037-4","article-title":"Pathogenesis of Bone Disease in Multiple Myeloma: From Bench to Bedside","volume":"8","author":"Terpos","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1182\/blood-2006-11-059188","article-title":"The Proteasome Inhibitor Bortezomib Affects Osteoblast Differentiation in Vitro and in Vivo in Multiple Myeloma Patients","volume":"110","author":"Giuliani","year":"2007","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1002\/jbmr.2741","article-title":"The Proteasome Inhibitor Bortezomib Maintains Osteocyte Viability in Multiple Myeloma Patients by Reducing Both Apoptosis and Autophagy: A New Function for Proteasome Inhibitors","volume":"31","author":"Toscani","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/leu.2012.183","article-title":"The Epoxyketone-Based Proteasome Inhibitors Carfilzomib and Orally Bioavailable Oprozomib Have Anti-Resorptive and Bone-Anabolic Activity in Addition to Anti-Myeloma Effects","volume":"27","author":"Hurchla","year":"2013","journal-title":"Leukemia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.exphem.2014.03.005","article-title":"Immunomodulatory Drugs Thalidomide and Lenalidomide Affect Osteoblast Differentiation of Human Bone Marrow Stromal Cells Invitro","volume":"42","author":"Bolomsky","year":"2014","journal-title":"Exp. Hematol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1038\/sj.leu.2404843","article-title":"The Effect of Novel Anti-Myeloma Agents on Bone Metabolism of Patients with Multiple Myeloma","volume":"21","author":"Terpos","year":"2007","journal-title":"Leukemia"},{"key":"ref_40","first-page":"129","article-title":"Osteoprogenitor Differentiation Is Not Affected by Immunomodulatory Thalidomide Analogs but Is Promoted by Low Bortezomib Concentration, While Both Agents Suppress Osteoclast Differentiation","volume":"33","author":"Munemasa","year":"2008","journal-title":"Int. J. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1182\/blood-2005-08-3450","article-title":"Thalidomide Derivative CC-4047 Inhibits Osteoclast Formation by down-Regulation of PU.1","volume":"107","author":"Anderson","year":"2006","journal-title":"Blood"},{"key":"ref_42","first-page":"9609","article-title":"Bone Formation Following Lenalidomide-Dexamethasone Combination Therapy in Cases of Multiple Myeloma Refractory to High-Dose Chemotherapy with Bortezomib and Autologous Peripheral Blood Stem Cell Transplantation: Report of a Case and Review of the Literat","volume":"8","author":"Sekiguchi","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1182\/blood.V114.22.1815.1815","article-title":"The Addition of Bortezomib to the Combination of Lenalidomide and Dexamethasone Increases Bone Formation in Relapsed\/Refractory Myeloma: A Prospective Study in 91 Patients","volume":"114","author":"Terpos","year":"2009","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1007\/s12185-012-1058-1","article-title":"Therapy with Lenalidomide plus Dexamethasone-Induced Bone Formation in a Patient with Refractory Multiple Myeloma","volume":"95","author":"Tsuda","year":"2012","journal-title":"Int. J. Hematol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e119","DOI":"10.1016\/S1470-2045(20)30559-3","article-title":"Treatment of Multiple Myeloma-Related Bone Disease: Recommendations from the Bone Working Group of the International Myeloma Working Group","volume":"22","author":"Terpos","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1038\/leu.2013.24","article-title":"Hypoxia-Inducible Factor (HIF)-1\u03b1 Suppression in Myeloma Cells Blocks Tumoral Growth in Vivo Inhibiting Angiogenesis and Bone Destruction","volume":"27","author":"Storti","year":"2013","journal-title":"Leukemia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e1008850","DOI":"10.1080\/2162402X.2015.1008850","article-title":"Modifications of the Mouse Bone Marrow Microenvironment Favor Angiogenesis and Correlate with Disease Progression from Asymptomatic to Symptomatic Multiple Myeloma","volume":"4","author":"Calcinotto","year":"2015","journal-title":"Oncoimmunology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/sj.leu.2404067","article-title":"Bone Marrow Angiogenesis in Multiple Myeloma","volume":"20","author":"Vacca","year":"2006","journal-title":"Leukemia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1158\/1535-7163.MCT-07-0311","article-title":"Zoledronic Acid Affects Over-Angiogenic Phenotype of Endothelial Cells in Patients with Multiple Myeloma","volume":"6","author":"Scavelli","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1158\/0008-5472.CAN-05-1195","article-title":"Bortezomib Mediates Antiangiogenesis in Multiple Myeloma via Direct and Indirect Effects on Endothelial Cells","volume":"66","author":"Roccaro","year":"2006","journal-title":"Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e143","DOI":"10.1038\/bcj.2013.38","article-title":"Pomalidomide: The New Immunomodulatory Agent for the Treatment of Multiple Myeloma","volume":"3","author":"Swaika","year":"2013","journal-title":"Blood Cancer J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.mvr.2008.08.003","article-title":"The Anti-Cancer Drug Lenalidomide Inhibits Angiogenesis and Metastasis via Multiple Inhibitory Effects on Endothelial Cell Function in Normoxic and Hypoxic Conditions","volume":"77","author":"Lu","year":"2009","journal-title":"Microvasc. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5334","DOI":"10.1200\/JCO.2005.03.723","article-title":"Thalidomide Downregulates Angiogenic Genes in Bone Marrow Endothelial Cells of Patients with Active Multiple Myeloma","volume":"23","author":"Vacca","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"100253","DOI":"10.1016\/j.jbo.2019.100253","article-title":"The Role of CXCR4 in Multiple Myeloma: Cells\u2019 Journey from Bone Marrow to beyond","volume":"17","author":"Ullah","year":"2019","journal-title":"J. Bone Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4341","DOI":"10.1182\/blood-2008-10-186668","article-title":"CXCR4 Inhibitor AMD3100 Disrupts the Interaction of Multiple Myeloma Cells with the Bone Marrow Microenvironment and Enhances Their Sensitivity to Therapy","volume":"113","author":"Azab","year":"2009","journal-title":"Blood"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1038\/sj.leu.2404658","article-title":"Neighboring Adipocytes Participate in the Bone Marrow Microenvironment of Multiple Myeloma Cells","volume":"21","author":"Caers","year":"2007","journal-title":"Leukemia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"34329","DOI":"10.18632\/oncotarget.6020","article-title":"Mature Adipocytes in Bone Marrow Protect Myeloma Cells against Chemotherapy through Autophagy Activation","volume":"6","author":"Liu","year":"2015","journal-title":"Oncotarget"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1182\/blood-2021-150208","article-title":"Bone Marrow Adipocyte Shapes Metabolism and Immunity in Tumor Microenvironment to Promote Multiple Myeloma","volume":"138","author":"Shu","year":"2021","journal-title":"Blood,"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1182\/blood-2012-06-430645","article-title":"Darwinian Evolution and Tiding Clones in Multiple Myeloma","volume":"120","author":"Bahlis","year":"2012","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1200\/JCO.2016.70.3348","article-title":"Intestinal Microbiota and Relapse after Hematopoietic-Cell Transplantation","volume":"35","author":"Peled","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1182\/bloodadvances.2019032276","article-title":"Minimal Residual Disease Negativity in Multiple Myeloma Is Associated with Intestinal Microbiota Composition","volume":"3","author":"Pianko","year":"2019","journal-title":"Blood Adv."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"632564","DOI":"10.3389\/fimmu.2021.632564","article-title":"Co-Evolution of Immune Response in Multiple Myeloma: Implications for Immune Prevention","volume":"12","author":"McCachren","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3336","DOI":"10.1158\/0008-5472.CAN-17-0502","article-title":"An Ex Vivo Platform for the Prediction of Clinical Response in Multiple Myeloma","volume":"77","author":"Silva","year":"2017","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"102716","DOI":"10.1016\/j.ebiom.2020.102716","article-title":"A Pharmacodynamic Model of Clinical Synergy in Multiple Myeloma","volume":"54","author":"Sudalagunta","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nrc775","article-title":"HeLa Cells 50 Years on: The Good, the Bad and the Ugly","volume":"2","author":"Masters","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Raulf, M. (2020). T cell: Primary culture from peripheral blood. Methods in Molecular Biology, Humana Press Inc.","DOI":"10.1007\/978-1-4939-9591-2_2"},{"key":"ref_67","first-page":"57370","article-title":"The Isolation and Culture of Primary Epicardial Cells Derived from Human Adult and Fetal Heart Specimens","volume":"134","author":"Dronkers","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Fitzgerald, A.A., Li, E., and Weiner, L.M. (2020). 3D Culture Systems for Exploring Cancer Immunology. Cancers, 13.","DOI":"10.3390\/cancers13010056"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Barbosa, M.A.G., Xavier, C.P.R., Pereira, R.F., Petrikait\u0117, V., and Vasconcelos, M.H. (2021). 3D Cell Culture Models as Recapitulators of the Tumor Microenvironment for the Screening of Anti-Cancer Drugs. Cancers, 14.","DOI":"10.3390\/cancers14010190"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1111\/joa.12257","article-title":"Advances in 3D Cell Culture Technologies Enabling Tissue-like Structures to Be Created in Vitro","volume":"227","author":"Knight","year":"2015","journal-title":"J. Anat."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S0092-8674(04)00255-7","article-title":"Socializing with the Neighbors: Stem Cells and Their Niche","volume":"116","author":"Fuchs","year":"2004","journal-title":"Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"9064","DOI":"10.1073\/pnas.89.19.9064","article-title":"Interaction with Basement Membrane Serves to Rapidly Distinguish Growth and Differentiation Pattern of Normal and Malignant Human Breast Epithelial Cells","volume":"89","author":"Petersen","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1038\/s41375-020-0785-1","article-title":"Evaluating the Efficacy of Multiple Myeloma Cell Lines as Models for Patient Tumors via Transcriptomic Correlation Analysis","volume":"34","author":"Sarin","year":"2020","journal-title":"Leukemia"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1600505","DOI":"10.1002\/biot.201600505","article-title":"Drug Screening in 3D in Vitro Tumor Models: Overcoming Current Pitfalls of Efficacy Read-Outs","volume":"12","author":"Santo","year":"2017","journal-title":"Biotechnol. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1158\/0008-5472.CAN-14-3400","article-title":"Metabolic Signature Identifies Novel Targets for Drug Resistance in Multiple Myeloma","volume":"75","author":"Maiso","year":"2015","journal-title":"Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Gavriatopoulou, M., Paschou, S.A., Ntanasis-stathopoulos, I., and Dimopoulos, M.A. (2021). Metabolic Disorders in Multiple Myeloma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111430"},{"key":"ref_77","first-page":"3015","article-title":"Deconstructing the Third Dimension-How 3D Culture Microenvironments Alter Cellular Cues","volume":"125","author":"Baker","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.copbio.2003.08.002","article-title":"Role of the Extracellular Matrix in Morphogenesis","volume":"14","author":"Kleinman","year":"2003","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_79","first-page":"203","article-title":"Comparison of Cancer Cells in 2D vs 3D Culture Reveals Differences in AKT-MTOR-S6K Signaling and Drug Responses","volume":"130","author":"Riedl","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_80","first-page":"593","article-title":"Animal Model of Human Disease. Multiple Myeloma","volume":"132","author":"Radl","year":"1988","journal-title":"Am. J. Pathol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1182\/blood.V92.8.2908","article-title":"Primary Myeloma Cells Growing in SCID-Hu Mice: A Model for Studying the Biology and Treatment of Myeloma and Its Manifestations","volume":"92","author":"Yaccoby","year":"1998","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.4049\/jimmunol.172.5.2731","article-title":"Of Mice and Not Men: Differences between Mouse and Human Immunology","volume":"172","author":"Mestas","year":"2004","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1038\/ng.3967","article-title":"Patient-Derived Xenografts Undergo Mouse-Specific Tumor Evolution","volume":"49","author":"Ha","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"7141","DOI":"10.1158\/0008-5472.CAN-11-1732","article-title":"Diversity of Human Leukemia Xenograft Mouse Models: Implications for Disease Biology","volume":"71","author":"Meyer","year":"2011","journal-title":"Cancer Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"m4087","DOI":"10.1136\/bmj.m4087","article-title":"Mortality Due to Cancer Treatment Delay: Systematic Review and Meta-Analysis","volume":"371","author":"Hanna","year":"2020","journal-title":"BMJ"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1146\/annurev.pathol.3.121806.154244","article-title":"Mouse Models of Cancer","volume":"6","author":"Cheon","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1038\/sj.bjc.6605642","article-title":"Guidelines for the Welfare and Use of Animals in Cancer Research","volume":"102","author":"Workman","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1084\/jem.15.5.516","article-title":"On the Permanent Life of Tissues Outside of the Organism","volume":"15","author":"Carrel","year":"1912","journal-title":"J. Exp. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1126\/science.560061","article-title":"Primary Bioassay of Human Tumor Stem Cells","volume":"197","author":"Hamburger","year":"1977","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"44045","DOI":"10.1038\/srep44045","article-title":"Engineering a Vascularised 3D in Vitro Model of Cancer Progression","volume":"7","author":"Magdeldin","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Wang, X., Sun, Q., and Pei, J. (2018). Microfluidic-Based 3D Engineered Microvascular Networks and Their Applications in Vascularized Microtumor Models. Micromachines, 9.","DOI":"10.3390\/mi9100493"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s00018-007-7356-8","article-title":"Spatially Defined Oxygen Gradients and Vascular Endothelial Growth Factor Expression in an Engineered 3D Cell Model","volume":"65","author":"Cheema","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3380","DOI":"10.1038\/s41596-020-0379-4","article-title":"Establishment of Patient-Derived Cancer Organoids for Drug-Screening Applications","volume":"15","author":"Driehuis","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_94","first-page":"69","article-title":"A Comparison of Cytokine Production in 2-Dimensional and 3-Dimensional Cultures of Bone Marrow Stromal Cells of Muliple Myeloma Patients in Response to RPMI8226 Myeloma Cells","volume":"47","author":"Piersiak","year":"2009","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.biomaterials.2015.09.017","article-title":"3D Tissue-Engineered Bone Marrow as a Novel Model to Study Pathophysiology and Drug Resistance in Multiple Myeloma","volume":"73","author":"Muz","year":"2015","journal-title":"Biomaterials"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"100040","DOI":"10.1016\/j.mtbio.2019.100040","article-title":"A Worm Gel-Based 3D Model to Elucidate the Paracrine Interaction between Multiple Myeloma and Mesenchymal Stem Cells","volume":"5","author":"Spelat","year":"2020","journal-title":"Mater. Today Bio."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1182\/blood-2008-02-142430","article-title":"A Unique Three-Dimensional Model for Evaluating the Impact of Therapy on Multiple Myeloma","volume":"112","author":"Kirshner","year":"2008","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1158\/0008-5472.CAN-07-3096","article-title":"Clonogenic Multiple Myeloma Progenitors, Stem Cell Properties, and Drug Resistance","volume":"68","author":"Matsui","year":"2008","journal-title":"Cancer Res."},{"key":"ref_99","first-page":"209","article-title":"Mesenchymal Stem Cells from Bone Marrow Regulate Invasion and Drug Resistance of Multiple Myeloma Cells by Secreting Chemokine CXCL13","volume":"20","author":"Zhang","year":"2020","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_100","first-page":"50947","article-title":"A Three-Dimensional Tissue Culture Model to Study Primary Human Bone Marrow and Its Malignancies","volume":"85","author":"Parikh","year":"2014","journal-title":"J. Vis. Exp."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Kirshner, J., Kirshnan, A., Nathwani, N., Htut, M., Rosenzweig, M., Karanes, C., Firoozeh, S., and Rosen, S. (2020, January 22\u201324). Reconstructed bone (r-bone): A patient-derived 3D culture platform for prediction of clinical outcomes in multiple myeloma. Proceedings of the Annual Meeting of the American Association for Cancer Research, Virtual.","DOI":"10.1158\/1538-7445.AM2020-330"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Huang, Y.H., Molavi, O., Alshareef, A., Haque, M., Wang, Q., Chu, M.P., Venner, C.P., Sandhu, I., Peters, A.C., and Lavasanifar, A. (2018). Constitutive Activation of STAT3 in Myeloma Cells Cultured in a Three-Dimensional, Reconstructed Bone Marrow Model. Cancers, 10.","DOI":"10.20944\/preprints201803.0151.v2"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3390\/cimb43010026","article-title":"Three-Dimensional Reconstructed Bone Marrow Matrix Culture Improves the Viability of Primary Myeloma Cells in-Vitro via a Stat3-Dependent Mechanism","volume":"43","author":"Huang","year":"2021","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1852517","DOI":"10.1155\/2017\/1852517","article-title":"Inflammatory and Anti-Inflammatory Equilibrium, Proliferative and Antiproliferative Balance: The Role of Cytokines in Multiple Myeloma","volume":"2017","author":"Musolino","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Caillot, M., Zylbersztejn, F., Maitre, E., Bourgeais, J., H\u00e9rault, O., and Sola, B. (2020). ROS Overproduction Sensitises Myeloma Cells to Bortezomib-Induced Apoptosis and Alleviates Tumour Microenvironment-Mediated Cell Resistance. Cells, 9.","DOI":"10.3390\/cells9112357"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.phrs.2016.01.029","article-title":"Oxidative Stress and Proteasome Inhibitors in Multiple Myeloma","volume":"105","author":"Lipchick","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1182\/blood.2019004537","article-title":"Immunogenomic Identification and Characterization of Granulocytic Myeloid-Derived Suppressor Cells in Multiple Myeloma","volume":"136","author":"Perez","year":"2020","journal-title":"Blood"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s40164-022-00296-9","article-title":"Myeloid-Derived Suppressor Cells in Hematologic Malignancies: Two Sides of the Same Coin","volume":"11","author":"Yu","year":"2022","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13045-019-0714-9","article-title":"Trabectedin Triggers Direct and NK-Mediated Cytotoxicity in Multiple Myeloma","volume":"12","author":"Siciliano","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Ali, J.Y.H., Fitieh, A.M., and Ismail, I.H. (2022). The Role of DNA Repair in Genomic Instability of Multiple Myeloma. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105688"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1111\/j.1582-4934.2009.00853.x","article-title":"Translating Tissue Engineering Technology Platforms into Cancer Research","volume":"13","author":"Hutmacher","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Khan, A.O., Colombo, M., Reyat, J.S., Wang, G., Rodriguez-Romera, A., Wen, W.X., Murphy, L., Grygielska, B., Mahoney, C., and Stone, A. (2022). Human Bone Marrow Organoids for Disease Modelling, Discovery and Validation of Therapeutic Targets in Hematological Malignancies. BioRxiv.","DOI":"10.1101\/2022.03.14.483815"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e1434465","DOI":"10.1080\/2162402X.2018.1434465","article-title":"Cellular Immunotherapy on Primary Multiple Myeloma Expanded in a 3D Bone Marrow Niche Model","volume":"7","author":"Braham","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"8105","DOI":"10.2147\/IJN.S184262","article-title":"Liposomal Drug Delivery in an in Vitro 3D Bone Marrow Model for Multiple Myeloma","volume":"13","author":"Braham","year":"2018","journal-title":"Int. J. Nanomedicine"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e003850","DOI":"10.1136\/jitc-2021-003850","article-title":"Gamma Delta TCR Anti-CD3 Bispecific Molecules (GABs) as Novel Immunotherapeutic Compounds","volume":"9","author":"Meringa","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e523","DOI":"10.3324\/haematol.2018.213355","article-title":"Possibilities and Limitations of an in Vitro Three-Dimensional Bone Marrow Model for the Prediction of Clinical Responses in Patients with Relapsed Multiple Myeloma","volume":"104","author":"Braham","year":"2019","journal-title":"Haematologica"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1089\/ten.tec.2017.0467","article-title":"Endosteal and Perivascular Subniches in a 3D Bone Marrow Model for Multiple Myeloma","volume":"24","author":"Braham","year":"2018","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"101015","DOI":"10.1016\/j.tranon.2021.101015","article-title":"3D Bioprinted Cancer Models: Revolutionizing Personalized Cancer Therapy","volume":"14","author":"Augustine","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1016\/j.clml.2019.09.045","article-title":"High Throughput 3D Bioprinting of Patient-Derived Multiple Myeloma Organoid Models for Niche Recapitulation and Chemosensitivity Assessment","volume":"19","author":"Rodriguez","year":"2019","journal-title":"Clin. Lymphoma. Myeloma Leuk."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e2100884","DOI":"10.1002\/adhm.202100884","article-title":"A 3D-Bioprinted Multiple Myeloma Model","volume":"11","author":"Wu","year":"2022","journal-title":"Adv. Healthc. Mater."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1901044","DOI":"10.1002\/admt.201901044","article-title":"Extrusion and Microfluidic-Based Bioprinting to Fabricate Biomimetic Tissues and Organs","volume":"5","author":"Davoodi","year":"2020","journal-title":"Adv. Mater. Technol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"21712","DOI":"10.1039\/C8RA03022G","article-title":"Bioprinting of 3D Tissues\/Organs Combined with Microfluidics","volume":"8","author":"Ma","year":"2018","journal-title":"RSC Adv."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.3892\/ijo.2013.2134","article-title":"Hypoxia Reduces CD138 Expression and Induces an Immature and Stem Cell-like Transcriptional Program in Myeloma Cells","volume":"43","author":"Kawano","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"6304","DOI":"10.1158\/0008-5472.CAN-04-1099","article-title":"Direct Assessment of Drug Penetration into Tissue Using a Novel Application of Three-Dimensional Cell Culture","volume":"64","author":"Kyle","year":"2004","journal-title":"Cancer Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1080\/10428194.2017.1319052","article-title":"Tariquidar Sensitizes Multiple Myeloma Cells to Proteasome Inhibitors via Reduction of Hypoxia-Induced P-Gp-Mediated Drug Resistance","volume":"58","author":"Muz","year":"2017","journal-title":"Leuk. Lymphoma"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Sun, J., Muz, B., Alhallak, K., Markovic, M., Gurley, S., Wang, Z., Guenthner, N., Wasden, K., Fiala, M., and King, J. (2020). Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma. Cancers, 12.","DOI":"10.3390\/cancers12020305"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"19343","DOI":"10.1038\/s41598-021-98760-9","article-title":"A Pilot Study of 3D Tissue-Engineered Bone Marrow Culture as a Tool to Predict Patient Response to Therapy in Multiple Myeloma","volume":"11","author":"Alhallak","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"77326","DOI":"10.18632\/oncotarget.12643","article-title":"A Novel 3D Mesenchymal Stem Cell Model of the Multiple Myeloma Bone Marrow Niche: Biologic and Clinical Applications","volume":"7","author":"Jakubikova","year":"2016","journal-title":"Oncotarget"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1007\/s00432-021-03854-6","article-title":"Ex Vivo Propagation in a Novel 3D High-Throughput Co-Culture System for Multiple Myeloma","volume":"148","author":"Waldschmidt","year":"2022","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"155358","DOI":"10.1016\/j.cyto.2020.155358","article-title":"Cytokine Profiles in Patients with Newly Diagnosed Multiple Myeloma: Survival Is Associated with IL-6 and IL-17A Levels","volume":"138","author":"Gu","year":"2021","journal-title":"Cytokine"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1182\/blood.V128.22.2109.2109","article-title":"Testing Novel Anti-Multiple Myeloma (MM) Agents in a Suitable Three-Dimensional (3D) Co-Culture Platform","volume":"128","author":"Waldschmidt","year":"2016","journal-title":"Blood"},{"key":"ref_132","first-page":"1793","article-title":"Epigenetic Modifications of the Bone Marrow (BM) Niche in Multiple Myeloma (MM)-a Three-Dimensional (3D) in Vitro Approach","volume":"130","author":"Wider","year":"2017","journal-title":"Blood"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1080\/10463356.2010.11883480","article-title":"3D Matrices for Anti-Cancer Drug Testing and Development","volume":"25","author":"Gurski","year":"2010","journal-title":"Oncol. Issues"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"119960","DOI":"10.1016\/j.biomaterials.2020.119960","article-title":"A Three-Dimensional Hyaluronic Acid-Based Niche Enhances the Therapeutic Efficacy of Human Natural Killer Cell-Based Cancer Immunotherapy","volume":"247","author":"Ahn","year":"2020","journal-title":"Biomaterials"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.ijbiomac.2021.06.174","article-title":"A Novel Platform for Drug Testing: Biomimetic Three-Dimensional Hyaluronic Acid-Based Scaffold Seeded with Human Hepatocarcinoma Cells","volume":"185","author":"Turtoi","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"112159","DOI":"10.1016\/j.colsurfb.2021.112159","article-title":"Photo-Crosslinked Hyaluronic Acid Hydrogel as a Biomimic Extracellular Matrix to Recapitulate in Vivo Features of Breast Cancer Cells","volume":"209","author":"Wang","year":"2022","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_137","first-page":"58176","article-title":"Hyaluronic-Acid Based Hydrogels for 3-Dimensional Culture of Patient-Derived Glioblastoma Cells","volume":"138","author":"Xiao","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_138","first-page":"67","article-title":"Characterization of Multiple Myeloma Clonal Cell Expansion and Stromal Wnt\/\u03b2-Catenin Signaling in Hyaluronic Acid-Based 3D Hydrogel","volume":"28","author":"Narayanan","year":"2014","journal-title":"In Vivo"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/ajh.25008","article-title":"The Role of Extracellular Matrix Stiffness in Megakaryocyte and Platelet Development and Function","volume":"93","author":"Leiva","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Ishihara, S., and Haga, H. (2022). Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors. Cancers, 14.","DOI":"10.3390\/cancers14041049"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/s41563-022-01294-2","article-title":"Directed Cell Migration towards Softer Environments","volume":"21","author":"Isomursu","year":"2022","journal-title":"Nat. Mater."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"100787","DOI":"10.1016\/j.blre.2020.100787","article-title":"The Extracellular Matrix: A Key Player in the Pathogenesis of Hematologic Malignancies","volume":"48","author":"Sidhu","year":"2021","journal-title":"Blood Rev."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Ferrarini, M., Steimberg, N., Ponzoni, M., Belloni, D., Berenzi, A., Girlanda, S., Caligaris-Cappio, F., Mazzoleni, G., and Ferrero, E. (2013). Ex-Vivo Dynamic 3-D Culture of Human Tissues in the RCCSTM Bioreactor Allows the Study of Multiple Myeloma Biology and Response to Therapy. PLoS ONE, 8.","DOI":"10.1371\/annotation\/d7d8e0a7-aa3d-4620-98e5-c5a7bbf31dc8"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/978-1-4939-7021-6_13","article-title":"3D-dynamic culture models of multiple myeloma","volume":"Volume 1612","author":"Ferrarini","year":"2017","journal-title":"Methods in Molecular Biology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"707","DOI":"10.3324\/haematol.2017.167486","article-title":"Modeling Multiple Myeloma-Bone Marrow Interactions and Response to Drugs in a 3D Surrogate Microenvironment","volume":"103","author":"Belloni","year":"2018","journal-title":"Haematologica"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1177\/039139889902201207","article-title":"Rotary Cell Culture System (RCCS): A New Method for Cultivating Hepatocytes on Microcarriers","volume":"22","author":"Mitteregger","year":"2000","journal-title":"Int. J. Artif. Organs"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/adt.2014.573","article-title":"Three-Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell-Based Biosensors","volume":"12","author":"Edmondson","year":"2014","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"3625","DOI":"10.1039\/C5TB00421G","article-title":"Microbead-Guided Reconstruction of the 3D Osteocyte Network during Microfluidic Perfusion Culture","volume":"3","author":"Gu","year":"2015","journal-title":"J. Mater. Chem. B"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1039\/C4LC00291A","article-title":"A Microfluidic-Based Platform for Tumour Spheroid Culture, Monitoring and Drug Screening","volume":"14","author":"Kwapiszewska","year":"2014","journal-title":"Lab Chip"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.4155\/bio.12.133","article-title":"Microfluidic 3D Cell Culture: Potential Application for Tissue-Based Bioassays","volume":"4","author":"Li","year":"2012","journal-title":"Bioanalysis"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1089\/ten.tec.2013.0490","article-title":"Patient-Specific 3D Microfluidic Tissue Model for Multiple Myeloma","volume":"20","author":"Zhang","year":"2014","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Zhang, W., Gu, Y., Sun, Q., Siegel, D.S., Tolias, P., Yang, Z., Lee, W.Y., and Zilberberg, J. (2015). Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the Optimization of the Osteoblastic Niche. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125995"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1039\/C5LC00341E","article-title":"Well Plate-Based Perfusion Culture Device for Tissue and Tumor Microenvironment Replication","volume":"15","author":"Zhang","year":"2015","journal-title":"Lab Chip"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.1182\/blood-2014-02-558007","article-title":"Investigating Osteogenic Differentiation in Multiple Myeloma Using a Novel 3D Bone Marrow Niche Model","volume":"124","author":"Reagan","year":"2014","journal-title":"Blood"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Xu, S., Santini, G.C., De Veirman, K., Broek, I.V., Leleu, X., De Becker, A., Van Camp, B., Vanderkerken, K., and Van Riet, I. (2013). Upregulation of MiR-135b Is Involved in the Impaired Osteogenic Differentiation of Mesenchymal Stem Cells Derived from Multiple Myeloma Patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079752"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.bone.2018.01.023","article-title":"Development of a 3D Bone Marrow Adipose Tissue Model","volume":"118","author":"Fairfield","year":"2019","journal-title":"Bone"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1016\/j.ajpath.2016.07.012","article-title":"Adipocyte-Lineage Cells Support Growth and Dissemination of Multiple Myeloma in Bone","volume":"186","author":"Trotter","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12976-016-0032-7","article-title":"A Mathematical Model of Tumor Growth and Its Response to Single Irradiation","volume":"13","author":"Watanabe","year":"2016","journal-title":"Theor. Biol. Med. Model."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Laleh, N.G., Loeffler, C.M.L., Grajek, J., Sta\u0148kov\u00e1, K., Pearson, A.T., Muti, H.S., Trautwein, C., Enderling, H., Poleszczuk, J., and Kather, J.N. (2022). Classical Mathematical Models for Prediction of Response to Chemotherapy and Immunotherapy. PLoS Comput. Biol., 18.","DOI":"10.1101\/2021.10.23.465549"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1158\/0008-5472.CAN-13-2397","article-title":"A Preclinical Assay for Chemosensitivity in Multiple Myeloma","volume":"74","author":"Khin","year":"2014","journal-title":"Cancer Res."},{"key":"ref_161","first-page":"e53070","article-title":"An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells","volume":"101","author":"Silva","year":"2015","journal-title":"J. Vis. Exp."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Akaike, H. (1974). Akaike, H. A new look at the statistical model identification. Selected Papers of Hirotugu Akaike, Springer.","DOI":"10.1007\/978-1-4612-1694-0_16"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1002\/ajh.26590","article-title":"Multiple Myeloma: 2022 Update on Diagnosis, Risk Stratification, and Management","volume":"97","author":"Rajkumar","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1080\/10428194.2017.1337115","article-title":"Overcoming Multiple Myeloma Drug Resistance in the Era of Cancer \u2018Omics","volume":"59","author":"Guang","year":"2018","journal-title":"\u2019 Leuk. Lymphoma"},{"key":"ref_165","first-page":"910","article-title":"2D and 3D Cell Cultures\u2014A Comparison of Different Types of Cancer Cell Cultures","volume":"14","author":"Kolenda","year":"2018","journal-title":"Arch. Med. Sci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1245\/s10434-019-08143-8","article-title":"Model of Patient-Specific Immune-Enhanced Organoids for Immunotherapy Screening: Feasibility Study","volume":"27","author":"Votanopoulos","year":"2019","journal-title":"Ann. Surg. Oncol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.biomaterials.2018.02.030","article-title":"3D-3-Culture: A Tool to Unveil Macrophage Plasticity in the Tumour Microenvironment","volume":"163","author":"Rebelo","year":"2018","journal-title":"Biomaterials"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s40425-019-0553-9","article-title":"Cocultures of Human Colorectal Tumor Spheroids with Immune Cells Reveal the Therapeutic Potential of MICA\/B and NKG2A Targeting for Cancer Treatment","volume":"7","author":"Courau","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0065-2776(06)90008-X","article-title":"Checkpoint Blockade in Cancer Immunotherapy","volume":"90","author":"Korman","year":"2006","journal-title":"Adv. Immunol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"603640","DOI":"10.3389\/fimmu.2020.603640","article-title":"3D Tumor Models and Their Use for the Testing of Immunotherapies","volume":"11","author":"Boucherit","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1002\/ijc.25781","article-title":"Multiple Uses of Basement Membrane-like Matrix (BME\/Matrigel) in Vitro and in Vivo with Cancer Cells","volume":"128","author":"Benton","year":"2011","journal-title":"Int. J. Cancer,"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.semcdb.2009.08.005","article-title":"Collagen-Based Cell Migration Models in Vitro and in Vivo","volume":"20","author":"Wolf","year":"2009","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"6103","DOI":"10.1039\/D1TB00963J","article-title":"Hyaluronic Acid-Based Hydrogels to Study Cancer Cell Behaviors","volume":"9","author":"Goodarzi","year":"2021","journal-title":"J. Mater. Chem. B"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1002\/jcp.10471","article-title":"From Cell-ECM Interactions to Tissue Engineering","volume":"199","author":"Rosso","year":"2004","journal-title":"J. Cell. Physiol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.canlet.2021.01.025","article-title":"Non-Matrigel Scaffolds for Organoid Cultures","volume":"504","author":"Kaur","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.drudis.2012.10.003","article-title":"Three-Dimensional Cell Culture: The Missing Link in Drug Discovery","volume":"18","author":"Breslin","year":"2013","journal-title":"Drug Discov. Today"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.semcancer.2005.05.004","article-title":"Matrigel: Basement Membrane Matrix with Biological Activity","volume":"15","author":"Kleinman","year":"2005","journal-title":"Semin. Cancer Biol."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Fallacara, A., Baldini, E., Manfredini, S., and Vertuani, S. (2018). Hyaluronic Acid in the Third Millennium. Polymers, 10.","DOI":"10.3390\/polym10070701"},{"key":"ref_179","first-page":"1","article-title":"3D Cell Culture On VitroGel System","volume":"1","author":"Huang","year":"2019","journal-title":"J. Cytol. Tissue Biol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1089\/ten.tea.2016.0127","article-title":"Regulation of Human Pluripotent Stem Cell-Derived Hepatic Cell Phenotype by Three-Dimensional Hydrogel Models","volume":"22","author":"Toivonen","year":"2016","journal-title":"Tissue Eng. Part A"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/978-1-60761-404-3_13","article-title":"Imaging and Analysis of Three-Dimensional Cell Culture Models","volume":"591","author":"Graf","year":"2010","journal-title":"Methods Mol. Biol.,"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.trecan.2021.06.009","article-title":"Tumour Microenvironment 3D-Modelling: Simplicity to Complexity and Back Again","volume":"7","author":"Carter","year":"2021","journal-title":"Trends Cancer"},{"key":"ref_183","unstructured":"(2022, May 10). Corning\u00ae Matrigel\u00ae Matrix Frequently Asked Questions. Available online: https:\/\/www.corning.com\/catalog\/cls\/documents\/faqs\/CLS-DL-CC-026.pdf."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3389\/fendo.2011.00015","article-title":"An Immunohistochemical Method to Study Breast Cancer Cell Subpopulations and Their Growth Regulation by Hormones in Three-Dimensional Cultures","volume":"2","author":"Pinto","year":"2011","journal-title":"Front. Endocrinol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.2217\/fon.13.274","article-title":"3D Tumor Models: History, Advances and Future Perspectives","volume":"10","author":"Benien","year":"2014","journal-title":"Future Oncol."},{"key":"ref_186","first-page":"275","article-title":"Techniques for Analysis, Sorting, and Dispensing of C. Elegans on the COPAS Flow-Sorting System","volume":"351","author":"Pulak","year":"2006","journal-title":"Methods Mol. Biol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"4432","DOI":"10.1182\/blood.V128.22.4432.4432","article-title":"Genomic Variability in Multiple Myeloma (MM) Patients By Race: An Analysis of the Publically Available Mmrf Commpass Study Database","volume":"128","author":"Paulus","year":"2016","journal-title":"Blood"},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"Awada, H., Thapa, B., Awada, H., Dong, J., Gurnari, C., Hari, P., and Dhakal, B. (2021). A Comprehensive Review of the Genomics of Multiple Myeloma: Evolutionary Trajectories, Gene Expression Profiling, and Emerging Therapeutics. Cells, 10.","DOI":"10.3390\/cells10081961"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.molonc.2014.09.011","article-title":"Next-Generation Clinical Trials: Novel Strategies to Address Thechallenge of Tumor Molecular Heterogeneity","volume":"9","author":"Catenacci","year":"2015","journal-title":"Mol. Oncol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"e530","DOI":"10.1038\/bcj.2017.14","article-title":"Discrepancies between the Percentage of Plasma Cells in Bone Marrow Aspiration and BM Biopsy: Impact on the Revised IMWG Diagnostic Criteria of Multiple Myeloma","volume":"7","author":"Lee","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"626805","DOI":"10.3389\/fcell.2021.626805","article-title":"A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies","volume":"9","author":"Serras","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1124\/dmd.118.082958","article-title":"Emerging Kidney Models to Investigate Metabolism, Transport, and Toxicity of Drugs and Xenobiotics","volume":"46","author":"Bajaj","year":"2018","journal-title":"Drug Metab. Dispos."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"8837","DOI":"10.1038\/s41598-017-08879-x","article-title":"Multi-Tissue Interactions in an Integrated Three-Tissue Organ-on-a-Chip Platform","volume":"7","author":"Skardal","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"25017","DOI":"10.1088\/1758-5090\/ab6d36","article-title":"Drug Compound Screening in Single and Integrated Multi-Organoid Body-on-a-Chip Systems","volume":"12","author":"Skardal","year":"2020","journal-title":"Biofabrication"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/21\/12888\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:02:34Z","timestamp":1760144554000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/21\/12888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,25]]},"references-count":194,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232112888"],"URL":"https:\/\/doi.org\/10.3390\/ijms232112888","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,25]]}}}