Increased Paracrine Immunomodulatory Potential of Mesenchymal Stromal Cells in Three-Dimensional Culture

TY - JOUR

T1 - Increased Paracrine Immunomodulatory Potential of Mesenchymal Stromal Cells in Three-Dimensional Culture

AU - Follin, Bjarke

AU - Juhl, Morten

AU - Cohen, Smadar

AU - Pedersen, Anders Elm

AU - Kastrup, Jens

AU - Ekblond, Annette

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

AB - 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.

U2 - 10.1089/ten.teb.2015.0532

DO - 10.1089/ten.teb.2015.0532

M3 - Journal article

C2 - 26861485

SN - 1937-3368

VL - 22

SP - 322

EP - 329

JO - Tissue Engineering - Part B: Reviews

JF - Tissue Engineering - Part B: Reviews

IS - 4

ER -