PT - JOURNAL ARTICLE AU - Stefanie Tietze AU - Martin Krater AU - Angela Jacobi AU - Anna Taubenberger AU - Maik Herbig AU - Rebekka Wehner AU - Marc Schmitz AU - Oliver Otto AU - Catrin List AU - Berna Kaya AU - Manja Wobus AU - Martin Bornhauser AU - Jochen Guck TI - Spheroid culture of mesenchymal stromal cells results in morpho-rheological properties appropriate for improved microcirculation AID - 10.1101/440966 DP - 2018 Jan 01 TA - bioRxiv PG - 440966 4099 - http://biorxiv.org/content/early/2018/10/11/440966.short 4100 - http://biorxiv.org/content/early/2018/10/11/440966.full AB - Human bone marrow mesenchymal stromal cells (MSCs) have been used in clinical trials for the treatment of systemic inflammatory diseases due to their regenerative and immunomodulatory properties. However, intravenous administration of MSCs is hampered by cell trapping within the pulmonary capillary networks. Here, we hypothesize that traditional twodimensional (2D) plastic-adherent cell expansion fails to result in appropriate morphorheological properties required for cell-circulation. To address this issue, we adapted a novel method to culture MSCs in non-adherent three-dimensional (3D) spheroids (mesenspheres). The biological properties of mesensphere-cultured MSCs remained identical to conventional 2D cultures. Morpho-rheological analyses revealed a smaller size and lower cell stiffness of mesensphere-derived MSCs compared to plastic-adherent MSCs, measured using real-time deformability cytometry (RT-DC) and atomic force microscopy, resulting in an increased ability to pass through micro-constrictions in an ex vivo microcirculation assay. This ability was confirmed in vivo by analysis of cell accumulation in various organ capillary networks after intravenous injection of mesensphere-derived MSCs in mouse. Our findings generally identify cellular morpho-rheological properties as attractive targets to improve microcirculation and specifically suggest mesensphere cultures as a promising approach for optimized MSC-based therapies.