Specificity of 3D MSC Spheroids Microenvironment: Impact on MSC Behavior and Properties
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Specificity of 3D MSC Spheroids Microenvironment: Impact on MSC Behavior and Properties Aleksandra Jauković 1 & Desislava Abadjieva 2 & Drenka Trivanović 1,3,4 & Elena Stoyanova 2 & Milena Kostadinova 2 & Shina Pashova 2 & Snejana Kestendjieva 2 & Tamara Kukolj 1 & Michal Jeseta 5,6 Elena Kistanova 2 & Milena Mourdjeva 2
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# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Mesenchymal stem cells (MSC) have been considered the promising candidates for the regenerative and personalized medicine due to their self-renewal potential, multilineage differentiation and immunomodulatory capacity. Although these properties have encouraged profound MSC studies in recent years, the majority of research has been based on standard 2D culture utilization. The opportunity to resemble in vivo characteristics of cells native niche has been provided by implementation of 3D culturing models such as MSC spheroid formation assesed through cells self-assembling. In this review, we address the current literature on physical and biochemical features of 3D MSC spheroid microenvironment and their impact on MSC properties and behaviors. Starting with the reduction in the cells’ dimensions and volume due to the changes in adhesion molecules expression and cytoskeletal proteins rearrangement resembling native conditions, through the microenvironment shifts in oxygen, nutrients and metabolites gradients and demands, we focus on distinctive and beneficial features of MSC in spheroids compared to cells cultured in 2D conditions. By summarizing the data for 3D MSC spheroids regarding cell survival, pluripotency, differentiation, immunomodulatory activities and potential to affect tumor cells growth we highlighted advantages and perspectives of MSC spheroids use in regenerative medicine. Further detailed analyses are needed to deepen our understanding of mechanisms responsible for modified MSC behavior in spheroids and to set future directions for MSC clinical application. Keywords Mesenchymal stem cells . 3D spheroids microenvironment . Morphological changes . Cell survival . Energy metabolism . Epigenetic regulation . Improved functionality
* Milena Mourdjeva [email protected]
Michal Jeseta [email protected]
Aleksandra Jauković [email protected] Desislava Abadjieva [email protected]
Elena Kistanova [email protected] 1
Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, PO BOX 102, Belgrade 11129, Serbia
2
Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, 73 Tzarigradsko shoes, 1113 Sofia, Bulgaria
3
IZKF Group Tissue Regeneration in Musculoskeletal Diseases, University Clinics, Röntgenring 11, D-97070 Wuerzburg, Germany
4
Bernhard-Heine-Center for Locomotion Research, University Wuerzburg, Wuerzburg, Germany
5
Department of Obstetrics and Gynecology, University Hospital and Masaryk University, Obilní trh 11, 602 00 Brno, Czech Republic
6
Department of Veterinary Sciences, Czech Universi
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