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NOTCH-Mediated Maintenance and Expansion of Human Bone Marrow Stromal/Stem Cells: A Technology Designed for Orthopedic Regenerative Medicine.

Publication ,  Journal Article
Dong, Y; Long, T; Wang, C; Mirando, AJ; Chen, J; O'Keefe, RJ; Hilton, MJ
Published in: Stem Cells Transl Med
December 2014

Human bone marrow-derived stromal/stem cells (BMSCs) have great therapeutic potential for treating skeletal disease and facilitating skeletal repair, although maintaining their multipotency and expanding these cells ex vivo have proven difficult. Because most stem cell-based applications to skeletal regeneration and repair in the clinic would require large numbers of functional BMSCs, recent research has focused on methods for the appropriate selection, expansion, and maintenance of BMSC populations during long-term culture. We describe here a novel biological method that entails selection of human BMSCs based on NOTCH2 expression and activation of the NOTCH signaling pathway in cultured BMSCs via a tissue culture plate coated with recombinant human JAGGED1 (JAG1) ligand. We demonstrate that transient JAG1-mediated NOTCH signaling promotes human BMSC maintenance and expansion while increasing their skeletogenic differentiation capacity, both ex vivo and in vivo. This study is the first of its kind to describe a NOTCH-mediated methodology for the maintenance and expansion of human BMSCs and will serve as a platform for future clinical or translational studies aimed at skeletal regeneration and repair.

Duke Scholars

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Published In

Stem Cells Transl Med

DOI

ISSN

2157-6564

Publication Date

December 2014

Volume

3

Issue

12

Start / End Page

1456 / 1466

Location

England

Related Subject Headings

  • Stromal Cells
  • Stem Cells
  • Signal Transduction
  • Serrate-Jagged Proteins
  • Regenerative Medicine
  • Receptor, Notch2
  • Orthopedics
  • Membrane Proteins
  • Jagged-1 Protein
  • Intercellular Signaling Peptides and Proteins
 

Citation

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Dong, Y., Long, T., Wang, C., Mirando, A. J., Chen, J., O’Keefe, R. J., & Hilton, M. J. (2014). NOTCH-Mediated Maintenance and Expansion of Human Bone Marrow Stromal/Stem Cells: A Technology Designed for Orthopedic Regenerative Medicine. Stem Cells Transl Med, 3(12), 1456–1466. https://doi.org/10.5966/sctm.2014-0034
Dong, Yufeng, Teng Long, Cuicui Wang, Anthony J. Mirando, Jianquan Chen, Regis J. O’Keefe, and Matthew J. Hilton. “NOTCH-Mediated Maintenance and Expansion of Human Bone Marrow Stromal/Stem Cells: A Technology Designed for Orthopedic Regenerative Medicine.Stem Cells Transl Med 3, no. 12 (December 2014): 1456–66. https://doi.org/10.5966/sctm.2014-0034.
Dong Y, Long T, Wang C, Mirando AJ, Chen J, O’Keefe RJ, et al. NOTCH-Mediated Maintenance and Expansion of Human Bone Marrow Stromal/Stem Cells: A Technology Designed for Orthopedic Regenerative Medicine. Stem Cells Transl Med. 2014 Dec;3(12):1456–66.
Dong, Yufeng, et al. “NOTCH-Mediated Maintenance and Expansion of Human Bone Marrow Stromal/Stem Cells: A Technology Designed for Orthopedic Regenerative Medicine.Stem Cells Transl Med, vol. 3, no. 12, Dec. 2014, pp. 1456–66. Pubmed, doi:10.5966/sctm.2014-0034.
Dong Y, Long T, Wang C, Mirando AJ, Chen J, O’Keefe RJ, Hilton MJ. NOTCH-Mediated Maintenance and Expansion of Human Bone Marrow Stromal/Stem Cells: A Technology Designed for Orthopedic Regenerative Medicine. Stem Cells Transl Med. 2014 Dec;3(12):1456–1466.

Published In

Stem Cells Transl Med

DOI

ISSN

2157-6564

Publication Date

December 2014

Volume

3

Issue

12

Start / End Page

1456 / 1466

Location

England

Related Subject Headings

  • Stromal Cells
  • Stem Cells
  • Signal Transduction
  • Serrate-Jagged Proteins
  • Regenerative Medicine
  • Receptor, Notch2
  • Orthopedics
  • Membrane Proteins
  • Jagged-1 Protein
  • Intercellular Signaling Peptides and Proteins