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Sustained release of bone morphogenetic protein 2 via coacervate improves the osteogenic potential of muscle-derived stem cells

Li, H and Johnson, NR and Usas, A and Lu, A and Poddar, M and wang, Y and Huard, J (2013) Sustained release of bone morphogenetic protein 2 via coacervate improves the osteogenic potential of muscle-derived stem cells. Stem Cells Translational Medicine, 2 (9). 667 - 677. ISSN 2157-6564

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Abstract

Muscle-derived stem cells (MDSCs) isolated from mouse skeletal muscle by a modified preplate technique exhibit long-term proliferation, high self-renewal, and multipotent differentiation capabilities in vitro. MDSCs retrovirally transduced to express bone morphogenetic proteins (BMPs) can differentiate into osteocytes and chondrocytes and enhance bone and articular cartilage repair in vivo, a feature that is not observed with nontransduced MDSCs. These results emphasize that MDSCs require prolonged exposure to BMPs to undergo osteogenic and chondrogenic differentiation. A sustained BMP protein delivery approach provides a viable and potentially more clinically translatable alternative to genetic manipulation of the cells. A unique growth factor delivery platform comprised of native heparin and a synthetic polycation, poly(ethylene argininylaspartate diglyceride) (PEAD), was used to bind, protect, and sustain the release of bone morphogenetic protein-2 (BMP2) in a temporally and spatially controlled manner. Prolonged exposure to BMP2 released by the PEAD:heparin delivery system promoted the differentiation of MDSCs to an osteogenic lineage in vitro and induced the formation of viable bone at an ectopic site in vivo. This new strategy represents an alternative approach for bone repair mediated by MDSCs while bypassing the need for gene therapy. © AlphaMed Press 2013.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Li, Hhol24@pitt.eduHOL24
Johnson, NR
Usas, A
Lu, A
Poddar, M
wang, Yyaw20@pitt.eduYAW20orcid.org/0000-0003-2067-382X
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > McGowan Institute for Regenerative Medicine
Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 1 January 2013
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: Stem Cells Translational Medicine
Volume: 2
Number: 9
Page Range: 667 - 677
DOI or Unique Handle: 10.5966/sctm.2013-0027
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Orthopaedic Surgery
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 2157-6564
PubMed Central ID: PMC3754467
Date Deposited: 31 Mar 2014 14:55
Last Modified: 03 Jan 2022 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/20798

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