Spheroid Culture of Mesenchymal Stem Cells

Abstract

Compared with traditional 2D adherent cell culture, 3D spheroidal cell aggregates, or spheroids, are regarded as more physiological, and this technique has been exploited in the field of oncology, stem cell biology, and tissue engineering. Mesenchymal stem cells (MSCs) cultured in spheroids have enhanced anti-inflammatory, angiogenic, and tissue reparative/regenerative effects with improved cell survival after transplantation. Cytoskeletal reorganization and drastic changes in cell morphology in MSC spheroids indicate a major difference in mechanophysical properties compared with 2D culture. Enhanced multidifferentiation potential, upregulated expression of pluripotency marker genes, and delayed replicative senescence indicate enhanced stemness in MSC spheroids. Furthermore, spheroid formation causes drastic changes in the gene expression profile of MSC in microarray analyses. In spite of these significant changes, underlying molecular mechanisms and signaling pathways triggering and sustaining these changes are largely unknown.

Long term morphological characterization of mesenchymal stromal cells 3D spheroids built with a rapid method based on entry-level equipment

“…Currently, there are more than 300 registered clinical trials (www.clinicaltrials.gov) in which MSC are used to treat several different diseases, with applications ranging from bone and cartilage repair to spinal cord, cardiac, and bladder regeneration (Kramer et al 2012). Three-dimensional (3D) MSC aggregates, typically known as ''spheroids'', have been demonstrated to improve several MSC features, such as multilineage potential, secretion of proangiogenic and chemotactic factors, resistance against hypoxic condition (Sart et al 2014), and, moreover, to enhance stemness (Cesarz and Tamama 2016) and anti-inflammatory properties (Ylöstalo et al 2012). Cellular spheroids are essentially micro-tissues built in vitro to resemble the native configuration of cells in vivo (Berenzi et al 2015), with a microenvironment that allows direct cell-cell signalling and cell-matrix interactions, thus better preserving MSC phenotype and innate properties (Bartosh et al 2010).…”

Cancer cells enter dormancy after cannibalizing mesenchymal stem/stromal cells (MSCs)

“…There has been a growing interest in using 3D nonadherent culture platforms to understand MSC biology better and enhance MSC-based therapies (22)(23)(24). By mirroring natural conditions in vivo, 3D cultures are superior to 2D cultures for understanding complex cell-to-cell and cell-to-matrix interactions, and therefore…”

Three-dimensional nanofiber scaffolds with arrayed holes for engineering skin tissue constructs

“…[24,25] The scaffolds can also combine with a variety of hydrogels or biologic matrices/cues to form 3D hybrid scaffolds with eliciting biologically functional molecules. [26][27][28] In addition, these novel 3D scaffolds with cost-effective fabrication could likely lead to the drastic change in the utilization of electrospun nanofibers.…”