Cell Mimicking Microparticles Influence the Organization, Growth, and Mechanophenotype of Stem Cell Spheroids.

作者: Nicholas R. Labriola , Jessica S. Sadick , Jeffrey R. Morgan , Edith Mathiowitz , Eric M. Darling

DOI: 10.1007/S10439-018-2028-4

关键词:

摘要: Substrate stiffness is known to alter cell behavior and drive stem differentiation, though most research in this area has been restricted traditional, two-dimensional culture systems rather than more physiologically relevant, three-dimensional (3D) platforms. In study, we utilized polymer-based, mimicking microparticles (CMMPs) deliver distinct, stable mechanical cues human adipose derived cells 3D spheroid examine changes adipogenic differentiation response mechanophenotype. After 21 days of induction, spheroids containing CMMPs (composite spheroids) stiffened accordance with CMMP elasticity such that the stiffest, ~ 10 kPa, were over 27% stiffer those incorporating compliant, ~ 0.25 kPa CMMPs. Adipogenically induced, cell-only 180% larger 50% compliant matched controls. Interestingly, composite cultured without chemical induction factors dissociated when presented ~ 1 kPa, while mitigated behavior. Gene expression for PPARG FABP4 upregulated 45-fold adipogenically induced samples compared controls but unaffected by elasticity, attributed insufficient cell-CMMP contacts throughout spheroid. summary, mechanically tuned influenced whole-spheroid mechanophenotype stability minimally affected response.

参考文章(38)
Justin R. Tse, Adam J. Engler, Preparation of Hydrogel Substrates with Tunable Mechanical Properties Current Protocols in Cell Biology. ,vol. 47, ,(2010) , 10.1002/0471143030.CB1016S47
Sarah B. Anderson, Chien-Chi Lin, Donna V. Kuntzler, Kristi S. Anseth, The performance of human mesenchymal stem cells encapsulated in cell-degradable polymer-peptide hydrogels Biomaterials. ,vol. 32, pp. 3564- 3574 ,(2011) , 10.1016/J.BIOMATERIALS.2011.01.064
D. Adam Young, Yu Suk Choi, Adam J. Engler, Karen L. Christman, Stimulation of adipogenesis of adult adipose-derived stem cells using substrates that mimic the stiffness of adipose tissue. Biomaterials. ,vol. 34, pp. 8581- 8588 ,(2013) , 10.1016/J.BIOMATERIALS.2013.07.103
Sapun H. Parekh, Kaushik Chatterjee, Sheng Lin-Gibson, Nicole M. Moore, Marcus T. Cicerone, Marian F. Young, Carl G. Simon, Modulus-Driven Differentiation of Marrow Stromal Cells in 3D Scaffolds That Is Independent of Myosin-based Cytoskeletal Tension Biomaterials. ,vol. 32, pp. 2256- 2264 ,(2011) , 10.1016/J.BIOMATERIALS.2010.11.065
S. Zauscher, F. Guilak, E.M. Darling, Viscoelastic properties of zonal articular chondrocytes measured by atomic force microscopy. Osteoarthritis and Cartilage. ,vol. 14, pp. 571- 579 ,(2006) , 10.1016/J.JOCA.2005.12.003
Qiu Li Loh, Cleo Choong, Three-dimensional scaffolds for tissue engineering applications : role of porosity and pore size Tissue Engineering Part B-reviews. ,vol. 19, pp. 485- 502 ,(2013) , 10.1089/TEN.TEB.2012.0437
Milind Singh, Casey P. Morris, Ryan J. Ellis, Michael S. Detamore, Cory Berkland, Microsphere-Based Seamless Scaffolds Containing Macroscopic Gradients of Encapsulated Factors for Tissue Engineering Tissue Engineering Part C-methods. ,vol. 14, pp. 299- 309 ,(2008) , 10.1089/TEN.TEC.2008.0167
Kentaro Hayashi, Yasuhiko Tabata, Preparation of stem cell aggregates with gelatin microspheres to enhance biological functions. Acta Biomaterialia. ,vol. 7, pp. 2797- 2803 ,(2011) , 10.1016/J.ACTBIO.2011.04.013
Alexander Kumachev, Jesse Greener, Ethan Tumarkin, Erika Eiser, Peter W. Zandstra, Eugenia Kumacheva, High-throughput generation of hydrogel microbeads with varying elasticity for cell encapsulation Biomaterials. ,vol. 32, pp. 1477- 1483 ,(2011) , 10.1016/J.BIOMATERIALS.2010.10.033
Eric M. Darling, Stefan Zauscher, Joel A. Block, Farshid Guilak, A Thin-Layer Model for Viscoelastic, Stress-Relaxation Testing of Cells Using Atomic Force Microscopy: Do Cell Properties Reflect Metastatic Potential? Biophysical Journal. ,vol. 92, pp. 1784- 1791 ,(2007) , 10.1529/BIOPHYSJ.106.083097