Matrix stiffness determines the fate of nucleus pulposus-derived stem cells

Yosi Navaro, Nadav Bleich-Kimelman, Lena Hazanov, Iris Mironi-Harpaz, Yonatan Shachaf, Shai Garty, Yoav Smith, Gadi Pelled, Dan Gazit, Dror Seliktar, Zulma Gazit

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Intervertebral disc (IVD) degeneration and consequent low-back pain present a major medical challenge. Nucleus pulposus-derived stem cells (NP-SCs) may lead to a novel therapy for this severe disease. It was recently shown that survival and function of mature NP cells are regulated in part by tissue stiffness. Wehypothesized that modification of matrix stiffness will influence the ability of cultured NP-SCs toproliferate, survive, and differentiate into mature NP cells. NP-SCs were subcultured in three-dimensional matrices of varying degrees of stiffness as measured by the material's shear storage modulus. Cell survival, activity, and rate of differentiation toward the chondrogenic or osteogenic lineage were analyzed. NP-SCs were found to proliferate and differentiate in all matrices, irrespective of matrix stiffness. However, matrices with a low shear storage modulus (G'=1kPa) promoted significantly more proliferation and chondrogenic differentiation, whereas matrices with a high modulus (G'=2kPa) promoted osteogenic differentiation. Imaging performed via confocal and scanning electron microscopes validated cell survival and highlighted stiffness-dependent cell-matrix interactions. These results underscorethe effect of the matrix modulus on the fate of NP-SCs. This research may facilitate elucidation of the complex cross-talk between NP-SCs and their surrounding matrix in healthy as well as pathological conditions.

Original languageEnglish
Pages (from-to)68-76
Number of pages9
JournalBiomaterials
Volume49
DOIs
StatePublished - 1 May 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Ltd.

Funding

We gratefully acknowledge funding support from the National Institutes of Health ( RO3 AR057143 , Z.G.), Israel Science Foundation grant ( no. 614/09 , D.G.) and the Sir Zelmen Cowen Universities Fund Blue Sky Research Grant (D.G.).

FundersFunder number
National Institutes of Health
National Institute of Arthritis and Musculoskeletal and Skin DiseasesR03AR057143
Israel Science Foundation614/09

    Keywords

    • Elasticity
    • Fibrinogen
    • Hydrogel
    • Intervertebral disc
    • Matrix stiffness
    • Stem cells

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