Dataset Information

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

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.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4907541 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Wang Yun Y Yu Xiaohua X Baker Christopher C Murphy William L WL McDevitt Todd C TC

Acta biomaterialia 20151024

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 demonstr ...[more]

PMID: 26597546

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Project description:Embryonic stem (ES) cells have been shown to recapitulate normal developmental stages. They are therefore a highly useful tool in the study of developmental biology. Profiling of ES cell-derived cells has yielded important information about the characteristics of differentiated cells, and allowed the identification of novel marker genes and pathways of differentiation. In this review, we focus on recent results from profiling studies of mouse embryos, human islets, and human ES cell-derived differentiated cells from several research groups. Global gene expression data from mouse embryos have been used to identify novel genes or pathways involved in the developmental process, and to search for transcription factors that regulate direct reprogramming. We introduce gene expression databases of human pancreas cells (Beta Cell Gene Atlas, EuroDia database), and summarize profiling studies of islet- or human ES cell-derived pancreatic cells, with a focus on gene expression, microRNAs, epigenetics, and protein expression. Then, we describe our gene expression profile analyses and our search for novel endoderm, or pancreatic, progenitor marker genes. We differentiated mouse ES cells into mesendoderm, definitive endoderm (DE), mesoderm, ectoderm, and Pdx1-expressing pancreatic lineages, and performed DNA microarray analyses. Genes specifically expressed in DE, and/or in Pdx1-expressing cells, were extracted and their expression patterns in normal embryonic development were studied by in situ hybridization. Out of 54 genes examined, 27 were expressed in the DE of E8.5 mouse embryos, and 15 genes were expressed in distinct domains in the pancreatic buds of E14.5 mouse embryos. Akr1c19, Aebp2, Pbxip1, and Creb3l1 were all novel, and none has been described as being expressed, either in the DE, or in the pancreas. By introducing the profiling results of ES cell-derived cells, the benefits of using ES cells to study early embryonic development will be discussed.

Dataset Information

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

Statement of significance

Publications

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

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