Biomimetic artificial bone marrow niches for the scale up of hematopoietic stem and progenitor cells
Year: 2025
Type: article
Abstract: Hematopoietic stem cell (HSC) transplantation to treat haematological disorders is greatly restricted by poor cell availability. Engineering of culture platforms that mimic the physiological properties of the bone marrow (BM) in a scalable format is important to enable the translation of HSC therapies. Here, we report the design of biomimetic BM niches enabling 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 bioemulsions assembled an interstitial matrix and secreted important factors critical to the maintenance of HSC phenotype. HSCs cultured in the resulting artificial BM niches maintained stemness whilst expanding significantly (>33-fold compared to suspension cultures) and enabling scale up of expansion in conical flask bioreactors (2 M cell batches). This platform harnesses engineered BM microenvironments and the processability of microdroplet technologies to produce HSCs in a scalable format, for application in cell-based therapies.
Source: Biomaterials
Authors: Minerva Bosch-Fortea, Daniele Marciano, Julien E. Gautrot
Institution: Queen Mary University of London
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,640
Funder: European Research Council
Awards: G5069867350, G6552793091
OpenAlex ID: W4413242894