Biomimetic Artificial Bone Marrow Niches for the Scale Up of Hematopoietic Stem Cells

Biomimetic Artificial Bone Marrow Niches for the Scale Up of Hematopoietic Stem Cells | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Biomimetic Artificial Bone Marrow Niches for the Scale Up of Hematopoietic Stem Cells Julien Gautrot, Minerva Bosch-Fortea, Daniele Marciano This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3121347/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Hematopoietic stem cell (HSC) transplantation to treat haematological disorders is greatly restricted by poor cell availability. Ex vivo expansion of HSCs as a strategy to overcome this limitation has shown limited success so far, due to the loss of stem cell properties in culture. Therefore, engineering of culture platforms that mimic the physiological properties of the bone marrow (BM) in a scalable format is an important target to enable the translation of HSC therapies. Here, we report the design of biomimetic BM niches that enable the culture of HSCs in a scalable 3D platform. Beyond cellular and biochemical components (e.g., matrix and growth factors), an important element of the BM microenvironment is its architecture, dense in adipocytes, with relatively limited matrix and anisotropic mechanical properties. To capture this context, we propose the use of bioemulsions 1,2 in which oil microdroplets and associated mechanical anisotropy recreate important architectural features of the hematopoietic niche. Mesenchymal stem cells (MSCs) grown at the surface of such bioemulsion remodelled this environment, assembling an interstitial matrix mimicking that of the BM microenvironment composition. In addition, MSCs secreted important factors underpinning the crosstalk between stromal cells and HSCs in the native environment. HSCs cultured in the resulting artificial BM niches maintained stemness whilst expanding significantly (> 33-fold compared to HSCs cultured in suspension) and enabling scale up of expansion in conical flask bioreactors, to produce 2M cells in a single batch. This platform therefore harnesses engineered BM microenvironments and the processability of bioemulsions and microdroplet technologies to produce HSCs in a scalable format, for application in cell-based therapies. Physical sciences/Materials science/Biomaterials/Bioinspired materials Biological sciences/Biotechnology/Stem-cell biotechnology Full Text Additional Declarations There is NO Competing Interest. Supplementary Files ArtificialBoneMarrowESI.pdf SuppvideoS1.mp4 Supplementary Video S1 SuppvideoS2.mp4 Supplementary Video S2 SuppvideoS3.avi Supplementary Video S3 Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3121347","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":215987162,"identity":"c0d56d84-b0a6-4beb-8ae7-cee1017b9137","order_by":0,"name":"Julien 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