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Engineering bone tissue from human embryonic stem cells.

ABSTRACT: In extensive bone defects, tissue damage and hypoxia lead to cell death, resulting in slow and incomplete healing. Human embryonic stem cells (hESC) can give rise to all specialized lineages found in healthy bone and are therefore uniquely suited to aid regeneration of damaged bone. We show that the cultivation of hESC-derived mesenchymal progenitors on 3D osteoconductive scaffolds in bioreactors with medium perfusion leads to the formation of large and compact bone constructs. Notably, the implantation of engineered bone in immunodeficient mice for 8 wk resulted in the maintenance and maturation of bone matrix, without the formation of teratomas that is consistently observed when undifferentiated hESCs are implanted, alone or in bone scaffolds. Our study provides a proof of principle that tissue-engineering protocols can be successfully applied to hESC progenitors to grow bone grafts for use in basic and translational studies.

SUBMITTER: Marolt D

PROVIDER: S-EPMC3365157 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Engineering bone tissue from human embryonic stem cells.

Marolt Darja D Campos Iván Marcos IM Bhumiratana Sarindr S Koren Ana A Petridis Petros P Zhang Geping G Spitalnik Patrice F PF Grayson Warren L WL Vunjak-Novakovic Gordana G

Proceedings of the National Academy of Sciences of the United States of America 20120514 22

In extensive bone defects, tissue damage and hypoxia lead to cell death, resulting in slow and incomplete healing. Human embryonic stem cells (hESC) can give rise to all specialized lineages found in healthy bone and are therefore uniquely suited to aid regeneration of damaged bone. We show that the cultivation of hESC-derived mesenchymal progenitors on 3D osteoconductive scaffolds in bioreactors with medium perfusion leads to the formation of large and compact bone constructs. Notably, the impl ...[more]

PMID: 22586099

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Project description:Despite the enthusiasm for bioengineering of functional renal tissues for transplantation, many obstacles remain before the potential of this technology can be realized in a clinical setting. Viable tissue engineering strategies for the kidney require identification of the necessary cell populations, efficient scaffolds, and the 3D culture conditions to develop and support the unique architecture and physiological function of this vital organ. Our studies have previously demonstrated that decellularized sections of rhesus monkey kidneys of all age groups provide a natural extracellular matrix (ECM) with sufficient structural properties with spatial and organizational influences on human embryonic stem cell (hESC) migration and differentiation. To further explore the use of decellularized natural kidney scaffolds for renal tissue engineering, pluripotent hESC were seeded in whole- or on sections of kidney ECM and cell migration and phenotype compared with the established differentiation assays for hESC. Results of qPCR and immunohistochemical analyses demonstrated upregulation of renal lineage markers when hESC were cultured in decellularized scaffolds without cytokine or growth factor stimulation, suggesting a role for the ECM in directing renal lineage differentiation. hESC were also differentiated with growth factors and compared when seeded on renal ECM or a new biologically inert polysaccharide scaffold for further maturation. Renal lineage markers were progressively upregulated over time on both scaffolds and hESC were shown to express signature genes of renal progenitor, proximal tubule, endothelial, and collecting duct populations. These findings suggest that natural scaffolds enhance expression of renal lineage markers particularly when compared to embryoid body culture. The results of these studies show the capabilities of a novel polysaccharide scaffold to aid in defining a protocol for renal progenitor differentiation from hESC, and advance the promise of tissue engineering as a source of functional kidney tissue.

Dataset Information

Engineering bone tissue from human embryonic stem cells.

Publications

Engineering bone tissue from human embryonic stem cells.

Similar Datasets

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