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Three-dimensional biomimetic scaffolds for hepatic differentiation of size-controlled embryoid bodies

Published online by Cambridge University Press:  12 March 2019

Yichun Wang Open the ORCID record for Yichun Wang [Opens in a new window] ,
Joong Hwan Bahng  and
Nicholas A. Kotov
Yichun Wang*
Affiliation:
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA; and Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
Joong Hwan Bahng
Affiliation:
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA; and Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
Nicholas A. Kotov
Affiliation:
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Material Science & Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA; and Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
*
a)Address all correspondence to this author. e-mail: [email protected]
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Abstract

Three-dimensional (3D) biomimetic scaffolds are critical for tissue engineering to support stem cell culture and organoid formation. Embryonic stem (ES) cells hold promising potential for tissue regeneration and ES cell-derived specific lineages are expected to be strongly influenced by the size of embryoid bodies (EBs). However, the fundamental knowledge needed to achieve the goal of highly reproducible, efficient, and scalable differentiation of how EB size affects differentiation is missing. Here, we used 3D biomimetic scaffolds with highly uniform porous structure to regulate size of EBs and differentiated them toward hepatic fate. The results showed EBs formed within the scaffolds were precisely controlled by pore sizes of the scaffolds. We found that EBs equals to or larger than 180 ± 27 µm maintained the ability to differentiate to hepatic lineage. The 3D biomimetic scaffold provides the effective tools toward accurate regulation of EB sizes for tissue engineering.

Keywords

biomaterialbiomedicalmicrostructure
Type
Article
Information
Journal of Materials Research , Volume 34 , Issue 8 , 29 April 2019 , pp. 1371 - 1380
Copyright
Copyright © Materials Research Society 2019 

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References

Murry, C.E. and Keller, G.: Differentiation of embryonic stem cells to clinically relevant populations: Lessons from embryonic development. Cell 132, 661–680 (2008).CrossRefGoogle ScholarPubMed
Wobus, A.M. and Boheler, K.R.: Embryonic stem cells: Prospects for developmental biology and cell therapy. Physiol. Rev. 85, 635–678 (2005).CrossRefGoogle ScholarPubMed
Burridge, P.W., Anderson, D., Priddle, H., Barbadillo Muñoz, M.D., Chamberlain, S., Allegrucci, C., Young, L.E., and Denning, C.: Improved human embryonic stem cell embryoid body homogeneity and cardiomyocyte differentiation from a novel V-96 plate aggregation system highlights interline variability. Stem Cells 25, 929–938 (2007).CrossRefGoogle ScholarPubMed
Messana, J.M., Hwang, N.S., Coburn, J., Elisseeff, J.H., and Zhang, Z.: Size of the embryoid body influences chondrogenesis of mouse embryonic stem cells. J. Tissue Eng. Regener. Med. 2, 499–506 (2008).CrossRefGoogle ScholarPubMed
Ng, E.S., Davis, R., Stanley, E.G., and Elefanty, A.G.: A protocol describing the use of a recombinant protein-based, animal product-free medium (APEL) for human embryonic stem cell differentiation as spin embryoid bodies. Nat. Protoc. 3, 768–776 (2008).CrossRefGoogle ScholarPubMed
Huang, C-C., Liao, C-K., Yang, M-J., Chen, C-H., Hwang, S-M., Hung, Y-W., Chang, Y., and Sung, H-W.: A strategy for fabrication of a three-dimensional tissue construct containing uniformly distributed embryoid body-derived cells as a cardiac patch. Biomaterials 31, 6218–6227 (2010).CrossRefGoogle ScholarPubMed
Ng, E.S., Davis, R.P., Azzola, L., Stanley, E.G., and Elefanty, A.G.: Forced aggregation of defined numbers of human embryonic stem cells into embryoid bodies fosters robust, reproducible hematopoietic differentiation. Blood 106, 1601–1603 (2005).CrossRefGoogle ScholarPubMed
Moon, S-H., Ju, J., Park, S-J., Bae, D., Chung, H-M., and Lee, S-H.: Optimizing human embryonic stem cells differentiation efficiency by screening size-tunable homogenous embryoid bodies. Biomaterials 35, 5987–5997 (2014).CrossRefGoogle ScholarPubMed
Cha, J.M., Bae, H., Sadr, N., Manoucheri, S., Edalat, F., Kim, K., Kim, S.B., Kwon, I.K., Hwang, Y-S., and Khademhosseini, A.: Embryoid body size-mediated differential endodermal and mesodermal differentiation using polyethylene glycol (PEG) microwell array. Macromol. Res. 23, 245–255 (2015).CrossRefGoogle Scholar
Sasaki, D., Shimizu, T., Masuda, S., Kobayashi, J., Itoga, K., Tsuda, Y., Yamashita, J.K., Yamato, M., and Okano, T.: Mass preparation of size-controlled mouse embryonic stem cell aggregates and induction of cardiac differentiation by cell patterning method. Biomaterials 30, 4384–4389 (2009).CrossRefGoogle ScholarPubMed
Dias, A.D., Unser, A.M., Xie, Y., Chrisey, D.B., and Corr, D.T.: Generating size-controlled embryoid bodies using laser direct-write. Biofabrication 6, 025007 (2014).CrossRefGoogle ScholarPubMed
Mohr, J.C., Zhang, J., Azarin, S.M., Soerens, A.G., de Pablo, J.J., Thomson, J.A., Lyons, G.E., Palecek, S.P., and Kamp, T.J.: The microwell control of embryoid body size in order to regulate cardiac differentiation of human embryonic stem cells. Biomaterials 31, 1885–1893 (2010).CrossRefGoogle ScholarPubMed
Choi, Y.Y., Chung, B.G., Lee, D.H., Khademhosseini, A., Kim, J-H., and Lee, S-H.: Controlled-size embryoid body formation in concave microwell arrays. Biomaterials 31, 4296–4303 (2010).CrossRefGoogle ScholarPubMed
Sakai, Y., Yoshiura, Y., and Nakazawa, K.: Embryoid body culture of mouse embryonic stem cells using microwell and micropatterned chips. J. Biosci. Bioeng. 111, 85–91 (2011).CrossRefGoogle ScholarPubMed
Vijayavenkataraman, S., Zhang, S., Lu, W.F., and Fuh, J.Y.H.: Electrohydrodynamic-jetting (EHD-Jet) 3D-printed functionally graded scaffolds for tissue engineering applications. J. Mater. Res. 33, 1999–2011 (2018).CrossRefGoogle Scholar
Bruyas, A., Lou, F., Stahl, A.M., Gardner, M., Maloney, W., Goodman, S., and Yang, Y.P.: Systematic characterization of 3D-printed PCL/β-TCP scaffolds for biomedical devices and bone tissue engineering: Influence of composition and porosity. J. Mater. Res. 33, 1948–1959 (2018).CrossRefGoogle ScholarPubMed
Hwang, Y-S., Chung, B.G., Ortmann, D., Hattori, N., Moeller, H-C., and Khademhosseini, A.: Microwell-mediated control of embryoid body size regulates embryonic stem cell fate via differential expression of WNT5a and WNT11. Proc. Natl. Acad. Sci. U. S. A. 106, 16978–16983 (2009).CrossRefGoogle ScholarPubMed
Michalopoulos, G.K.: Liver regeneration: Alternative epithelial pathways. Int. J. Biochem. Cell Biol. 43, 173–179 (2011).CrossRefGoogle ScholarPubMed
Wang, Y., Bahng, J.H., Che, Q., Han, J., and Kotov, N.A.: Anomalously fast diffusion of targeted carbon nanotubes in cellular spheroids. ACS Nano 9, 8231–8238 (2015).CrossRefGoogle ScholarPubMed
Lee, J., Cuddihy, M.J., Cater, G.M., and Kotov, N.A.: Engineering liver tissue spheroids with inverted colloidal crystal scaffolds. Biomaterials 30, 4687–4694 (2009).CrossRefGoogle ScholarPubMed
Carpenter, R.A., Kwak, J-G., Peyton, S.R., and Lee, J.: Implantable pre-metastatic niches for the study of the microenvironmental regulation of disseminated human tumour cells. Nat. Biomed. Eng. 2, 915–929 (2018).CrossRefGoogle Scholar
Griffith, L.G. and Swartz, M.A.: Capturing complex 3D tissue physiology in vitro. Nat. Rev. Mol. Cell Biol. 7, 211–224 (2006).CrossRefGoogle ScholarPubMed
Duarte, A.R.C., Mano, J.F., and Reis, R.L.: Thermosensitive polymeric matrices for three-dimensional cell culture strategies. Acta Biomater. 7, 526–529 (2011).CrossRefGoogle ScholarPubMed
Goral, V.N., Hsieh, Y-C., Petzold, O.N., Clark, J.S., Yuen, P.K., and Faris, R.A.: Perfusion-based microfluidic device for three-dimensional dynamic primary human hepatocyte cell culture in the absence of biological or synthetic matrices or coagulants. Lab Chip 10, 3380 (2010).CrossRefGoogle ScholarPubMed
Wang, Y., Jan, E., Cuddihy, M., Bahng, J.H., and Kotov, N.: Layered biomimetic nanocomposites replicate bone surface in three-dimensional cell cultures. Nanocomposites, 4, 155–156 (2019).Google Scholar
Podsiadlo, P., Kaushik, A.K., Shim, B.S., Agarwal, A., Tang, Z., Waas, A.M., Arruda, E.M., and Kotov, N.A.: Can nature’s design Be improved upon? High strength, transparent nacre-like nanocomposites with double network of sacrificial cross links. J. Phys. Chem. B 112, 14359–14363 (2008).CrossRefGoogle ScholarPubMed
Fineout-Overholt, E., Levin, R.F., and Melnyk, B.M.: Strategies for advancing evidence-based practice in clinical settings. J. N. Y. State Nurses. Assoc. 35, 28–32 (2004).Google Scholar
Solter, D. and Knowles, B.B.: Monoclonal antibody defining a stage-specific mouse embryonic antigen (SSEA-1). Proc. Natl. Acad. Sci. U. S. A. 75, 5565–5569 (1978).CrossRefGoogle Scholar
Matoba, R., Niwa, H., Masui, S., Ohtsuka, S., Carter, M.G., Sharov, A.A., and Ko, M.S.H.: Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression profiling. PLoS One 1, e26 (2006).CrossRefGoogle ScholarPubMed
Vassilieva, S., Guan, K., Pich, U., and Wobus, A.M.: Establishment of SSEA-1- and Oct-4-expressing rat embryonic stem-like cell lines and effects of cytokines of the IL-6 family on clonal growth. Exp. Cell Res. 258, 361–373 (2000).CrossRefGoogle ScholarPubMed
Marani, E., van Oers, J.W., Tetteroo, P.A., Poelmann, R.E., van der Veeken, J., and Deenen, M.G.: Stage specific embryonic carbohydrate surface antigens of primordial germ cells in mouse embryos: FAL (S.S.E.A.-1) and globoside (S.S.E.A.-3). Acta Morphol. Neerl.-Scand. 24, 103–110 (1986).Google Scholar
Niwa, H., Miyazaki, J., and Smith, A.G.: Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat. Genet. 24, 372–376 (2000).CrossRefGoogle ScholarPubMed
Schwartz, R.E., Linehan, J.L., Painschab, M.S., Hu, W-S., Verfaillie, C.M., and Kaufman, D.S.: Defined conditions for development of functional hepatic cells from human embryonic stem cells. Stem Cells Dev. 14, 643–655 (2005).CrossRefGoogle ScholarPubMed
Capo-chichi, C.D., Rula, M.E., Smedberg, J.L., Vanderveer, L., Parmacek, M.S., Morrisey, E.E., Godwin, A.K., and Xu, X-X.: Perception of differentiation cues by GATA factors in primitive endoderm lineage determination of mouse embryonic stem cells. Dev. Biol. 286, 574–586 (2005).CrossRefGoogle ScholarPubMed
Lange, C., Bassler, P., Lioznov, M.V., Bruns, H., Kluth, D., Zander, A.R., and Fiegel, H.C.: Hepatocytic gene expression in cultured rat mesenchymal stem cells. Transplant. Proc. 37, 276–279 (2005).CrossRefGoogle ScholarPubMed
Ben-Ze’ev, A., Robinson, G.S., Bucher, N.L., and Farmer, S.R.: Cell-cell and cell-matrix interactions differentially regulate the expression of hepatic and cytoskeletal genes in primary cultures of rat hepatocytes. Proc. Natl. Acad. Sci. U. S. A. 85, 2161–2165 (1988).CrossRefGoogle ScholarPubMed
Zhu, S., Rezvani, M., Harbell, J., Mattis, A.N., Wolfe, A.R., Benet, L.Z., Willenbring, H., and Ding, S.: Mouse liver repopulation with hepatocytes generated from human fibroblasts. Nature 508, 93–97 (2014).CrossRefGoogle ScholarPubMed
Lee, Y-C., Chang, C-J., Bali, D., Chen, Y-T., and Yan, Y-T.: Glycogen-branching enzyme deficiency leads to abnormal cardiac development: Novel insights into glycogen storage disease IV. Hum. Mol. Genet. 20, 455–465 (2011).CrossRefGoogle ScholarPubMed