{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T10:01:25Z","timestamp":1781604085801,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,2,18]],"date-time":"2011-02-18T00:00:00Z","timestamp":1297987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peripheral lymphoid organs (PLOs), the primary sites of development of adaptive immune responses, display a complex structural organization reflecting separation of cellular subsets (e.g., T and B lymphocytes) and functional compartments which is critical for immune function. The generation of in vitro culture systems capable of recapitulating salient features of PLOs for experimental, biotechnological, and clinical applications would be highly desirable, but has been hampered so far by the complexity of these systems. We have previously developed a three\u2010dimensional bioreactor system for long\u2010term, functional culture of human bone marrow cells on macroporous microspheres in a packed\u2010bed bioreactor with frequent medium change. Here we adapt the same system for culture of human primary cells from PLOs (tonsil) in the absence of specific exogenous growth factors or activators. Cells in this system displayed higher viability over several weeks, and maintain population diversity and cell surface markers largely comparable to primary cells. Light microscopy showed cells organizing in large diverse clusters within the scaffold pores and presence of B cell\u2010enriched areas. Strikingly, these cultures generated a significant number of antibody\u2010producing B cells when challenged with a panel of diverse antigens, as expected from a lymphoid tissue. Thus the three\u2010dimensional tonsil bioreactor culture system may serve as a useful model of PLOs by recapitulating their structural organization and function ex vivo. Biotechnol. Bioeng. 2011; 108:1430\u20131440. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/bit.23055","type":"journal-article","created":{"date-parts":[[2011,1,18]],"date-time":"2011-01-18T10:01:31Z","timestamp":1295344891000},"page":"1430-1440","source":"Crossref","is-referenced-by-count":17,"title":["Long\u2010term immunologically competent human peripheral lymphoid tissue cultures in a 3D bioreactor"],"prefix":"10.1002","volume":"108","author":[{"given":"Igor","family":"Kuzin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safiekhatoon","family":"Moshkani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Mantalaris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.H. David","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Bottaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,2,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2000.00912.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1398-9995.2002.1o3321.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.7.3610"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.30116"},{"issue":"3","key":"e_1_2_6_6_1","first-page":"428","article-title":"Site\u2010directed primary in vitro immunization: Production of HIV\u20101 neutralizing human monoclonal antibodies from lymphocytes obtained from seronegative donors","volume":"81","author":"Chin LT","year":"1994","journal-title":"Immunology"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-7-51"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2003.12.015"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1330"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-124-7-199604010-00006"},{"issue":"10","key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"4793","DOI":"10.4049\/jimmunol.159.10.4793","article-title":"Induction of parasite antigen\u2010specific antibody responses in unsensitized human B cells is dependent on the presence of cytokines after T cell priming","volume":"159","author":"Garraud O","year":"1997","journal-title":"J Immunol"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1594.2006.00303.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2010.03.001"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb00954.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2008.01.010"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1413.004"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200626255"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2414"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.12.2157"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041204"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(02)00201-6"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/73.1.13"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2009.03237.x"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/bp970136"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2003.09.020"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2006.02.005"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30379"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1263\/jbb.100.28"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/362355a0"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.05.006"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmat2441"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090257"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5388.480"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2007.12.006"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1039"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2009.09.006"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20471"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(10)05005-4"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2008.07.008"},{"issue":"1","key":"e_1_2_6_40_1","first-page":"26","article-title":"Multilineal hematopoiesis in a three\u2010dimensional murine long\u2010term bone marrow culture","volume":"23","author":"Wang TY","year":"1995","journal-title":"Exp Hematol"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(96)00207-4"}],"container-title":["Biotechnology and Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbit.23055","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.23055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:04:11Z","timestamp":1759925051000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bit.23055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2,18]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,6]]}},"alternative-id":["10.1002\/bit.23055"],"URL":"https:\/\/doi.org\/10.1002\/bit.23055","archive":["Portico"],"relation":{},"ISSN":["0006-3592","1097-0290"],"issn-type":[{"value":"0006-3592","type":"print"},{"value":"1097-0290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2,18]]}}}