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Dedicated microenvironmental niches in the BM provide PCs with biomechanical and soluble factors that support their long-term survival. There is a high need for appropriate and robust model systems to better understand PCs biology, to develop new therapeutic strategies for PCs-related diseases and perform targeted preclinical studies with high predictive value. Most preclinical data have been derived from <jats:italic>in vivo<\/jats:italic> studies in mice, as <jats:italic>in vitro<\/jats:italic> studies of human PCs are limited due to restricted survival and functionality in conventional 2D cultures that do not reflect the unique niche architecture of the BM. We have developed a microphysiological, dynamic 3D BM culture system (BM-MPS) based on human primary tissue (femoral biopsies), mechanically supported by a hydrogel scaffold casing. While a bioinert agarose casing did not support PCs survival, a photo-crosslinked collagen-hyaluronic acid (Col-HA) hydrogel preserved the native BM niche architecture and allowed PCs survival <jats:italic>in vitro<\/jats:italic> for up to 2 weeks. Further, the Col-HA hydrogel was permissive to lymphocyte migration into the microphysiological system\u00b4s circulation. Long-term PCs survival was related to the stable presence in the culture of soluble factors, as APRIL, BAFF, and IL-6. Increasing immunoglobulins concentrations in the medium confirm their functionality over culture time. To the best of our knowledge, this study is the first report of successful long-term maintenance of primary-derived non-malignant PCs <jats:italic>in vitro<\/jats:italic>. Our innovative model system is suitable for in-depth <jats:italic>in vitro<\/jats:italic> studies of human PCs regulation and exploration of targeted therapeutic approaches such as CAR-T cell therapy or biologics.<\/jats:p>","DOI":"10.1088\/1758-5090\/ad5dfe","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T22:42:37Z","timestamp":1719960157000},"page":"045005","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Long-term in vitro maintenance of plasma cells in a hydrogel-enclosed human bone marrow microphysiological 3D model system"],"prefix":"10.1088","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3084-3514","authenticated-orcid":true,"given":"Stefania","family":"Martini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6562-2351","authenticated-orcid":true,"given":"Norman Michael","family":"Drzeniek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Stark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8193-9631","authenticated-orcid":true,"given":"Matthias Reiner","family":"Kollert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijie","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Reinke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Ort","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Hardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iuliia","family":"Kotko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas","family":"Kath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3142-2890","authenticated-orcid":true,"given":"Stephan","family":"Schlickeiser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Gei\u00dfler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2189-3579","authenticated-orcid":true,"given":"Dimitrios Laurin","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna-Catharina","family":"Krebs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Dieter","family":"Volk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2024,7,12]]},"reference":[{"key":"bfad5dfebib1","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1097\/MOH.0000000000000621","article-title":"Structural organization of the bone marrow and its role in hematopoiesis","volume":"28","author":"Lucas","year":"2021","journal-title":"Curr. 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Published by IOP Publishing Ltd","name":"copyright_information","label":"Copyright Information"},{"value":"2023-10-16","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2024-07-01","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2024-07-12","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}