title: Increased Paracrine Immunomodulatory Potential of Mesenchymal Stromal Cells in Three-Dimensional Culture.
abstract: Mesenchymal stromal/stem cells (MSCs) have been investigated extensively through the past years, proving to have great clinical therapeutic potential. In vitro cultivation of MSCs in three-dimensional (3D) culture systems, such as scaffolds, hydrogels, or spheroids, have recently gained attention for tissue engineering applications. Studies on MSC spheroids demonstrated that such cultivation increased the paracrine immunomodulatory potential of the MSCs, accompanied by phenotypic alterations. In this review, we gather results from recent experimental studies on the immunomodulatory abilities of MSCs when cultured as spheroids or in biomaterials like scaffolds or hydrogels compared to regular two-dimensional (2D) culture and show that alterations occurring to MSCs in spheroids also occur in MSCs in biomaterials. We provide a brief description of known mechanisms of MSC immunomodulatory capacity and how they are altered in the two 3D culture systems, together with phenotypic cellular changes. Based on the present knowledge, we highlight vital areas in need of further investigation. The impact of 3D environments on immunomodulation has great potential for tissue engineering and cellular therapy, and this is the first review to gather this knowledge with a comparison across different 3D environments.
authors: 1 Cardiology Stem Cell Center, The Heart Center, Rigshospitalet, Copenhagen University Hospital , Copenhagen, Denmark .
authors: Bjarke
authors: B
authors: Follin
authors: 1 Cardiology Stem Cell Center, The Heart Center, Rigshospitalet, Copenhagen University Hospital , Copenhagen, Denmark .
authors: Morten
authors: M
authors: Juhl
authors: 2 Regenerative Medicine and Stem Cell Research Center, the Avram and Stella Goldstein-Goren Department of Biotechnology and Engineering, Ben-Gurion University of the Negev , Beer Sheva, Israel .
authors: Smadar
authors: S
authors: Cohen
authors: 3 Department of Immunology and Microbiology, University of Copenhagen , Copenhagen, Denmark .
authors: Anders Elm
authors: AE
authors: Pedersen
authors: 1 Cardiology Stem Cell Center, The Heart Center, Rigshospitalet, Copenhagen University Hospital , Copenhagen, Denmark .
authors: Jens
authors: J
authors: Kastrup
authors: 1 Cardiology Stem Cell Center, The Heart Center, Rigshospitalet, Copenhagen University Hospital , Copenhagen, Denmark .
authors: Annette
authors: A
authors: Ekblond
mesh_terms: D001672:Biocompatible Materials; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D020100:Hydrogels; D056747:Immunomodulation; D059630:Mesenchymal Stem Cells; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels