Mineral particles modulate osteo-chondrogenic differentiation of embryonic stem cell aggregates

• Type of Material: Article
• Authors: Yun Wang, Gladstone Institute of Cardiovascular Disease; Xiaohua Yu, University of Wisconsin-Madison; Christopher Baker, Georgia Institute of Technology; William L. Murphy, University of Wisconsin; Todd McDevitt, Emory University
• Language: English
• Date: 2016-01-01
• Publisher: Elsevier Ltd.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.actbio.2015.10.039
• Title of Journal or Parent Work: Acta Biomaterialia
• Volume: 29
• Start Page: 42
• End Page: 51
• Grant/Funding Information: This research was supported by the National Institutes of Health (R01GM088291 and R01AR059916).
• Keywords: Materials Science; Growth; Bone regeneration; Directed differentiation; Embryonic stem cells; Differentiation; Self formation; Morphogenesis; Microparticles; Chondrocytes; Technology; Materials Science, Biomaterials; Engineering; Calcium phosphate; Delivery; Scaffold; Engineering, Biomedical; Science & Technology; Osteo-chondrogenesis; Mineral microparticles
• Research Categories: Biology, Microbiology; Biology, Cell; Health Sciences, Rehabilitation and Therapy; Engineering, Biomedical

Abstract

Pluripotent stem cell aggregates offer an attractive approach to emulate embryonic morphogenesis and skeletal development. Calcium phosphate (CaP) based biomaterials have been shown to promote bone healing due to their osteoconductive and potential osteoinductive properties. In this study, we hypothesized that incorporation of CaP-coated hydroxyapatite mineral particles (MPs) within murine embryonic stem cell (ESC) aggregates could promote osteo-chondrogenic differentiation. Our results demonstrated that MP alone dose-dependently promoted the gene expression of chondrogenic and early osteogenic markers. In combination with soluble osteoinductive cues, MPs enhanced the hypertrophic and osteogenic phenotype, and mineralization of ESC aggregates. Additionally, MPs dose-dependently reduced ESC pluripotency and thereby decreased the size of teratomas derived from MP-incorporated ESC aggregates in vivo. Our data suggested a novel yet simple means of using mineral particles to control stem cell fate and create an osteochondral niche for skeletal tissue engineering applications. Statement of Significance Directing stem cell differentiation and morphogenesis via biomaterials represents a novel strategy to promote cell fates and tissue formation. Our study demonstrates the ability of calcium phosphate-based mineral particles to promote osteochondrogenic differentiation of embryonic stem cell aggregates as well as modulate teratoma formation in vivo. This hybrid biomaterial-ESC aggregate approach serves as an enabling platform to evaluate the ability of biomaterials to regulate stem cell fate and regenerate functional skeletal tissues for clinical applications.