Combination of Heparin Binding Peptide and Heparin Cell Surface Coatings for Mesenchymal Stem Cell Spheroid Assembly

• Type of Material: Article
• Authors: Jennifer Lei, Georgia Institute of Technology; William L Murphy, University of Wisconsin; Johnna Temenoff, Emory University
• Language: English
• Date: 2018-04-01
• Publisher: AMER CHEMICAL SOC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 American Chemical Society.
• Final Published Version (URL): http://dx.doi.org/10.1021/acs.bioconjchem.7b00757
• Title of Journal or Parent Work: Bioconjugate Chemistry
• Volume: 29
• Issue: 4
• Start Page: 878
• End Page: 884
• Grant/Funding Information: This work was supported by an NSF DMR (1207045) grant awarded to JST, and grants from the National Institutes of Health (R01HL093282) and Environmental Protection Agency (835737) to WLM.; The human MSCs employed in these studies were provided by the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White through a grant from NCRR of the NIH, Grant #P40RR017447.
• Keywords: TISSUE; FIBROBLAST GROWTH-FACTOR; MICROTISSUES; Life Sciences & Biomedicine; OSTEOBLASTS; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; RECEPTOR; Biochemical Research Methods; ANGIOGENESIS; MICROMOLDED NONADHESIVE HYDROGELS; Chemistry, Organic; Biochemistry & Molecular Biology; PANCREATIC-ISLETS; Chemistry; CULTURE
• Research Categories: Engineering, Biomedical; Chemistry, Biochemistry; Health Sciences, Medicine and Surgery

Abstract

Microtissues containing multiple cell types have been used in both in vitro models and in vivo tissue repair applications. However, to improve throughput, there is a need to develop a platform that supports self-assembly of a large number of 3D microtissues containing multiple cell types in a dynamic suspension system. Thus, the objective of this study was to exploit the binding interaction between the negatively charged glycosaminoglycan, heparin, and a known heparin binding peptide to establish a method that promotes assembly of mesenchymal stem cell (MSC) spheroids into larger aggregates. We characterized heparin binding peptide (HEPpep) and heparin coatings on cell surfaces and determined the specificity of these coatings in promoting assembly of MSC spheroids in dynamic culture. Overall, combining spheroids with both coatings promoted up to 70 ± 11% of spheroids to assemble into multiaggregate structures, as compared to only 10 ± 4% assembly when cells having the heparin coating were cultured with cells coated with a scrambled peptide. These results suggest that this self-assembly method represents an exciting approach that may be applicable for a wide range of applications in which cell aggregation is desired.