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Research article2015Peer reviewed

Indications of that migration of stem cells is influenced by the extra cellular matrix architecture in the mammalian intervertebral disk region

Henriksson, Helena Barreto; Papadimitriou, N; Tschernitz, S; Svala, Emilia; Skiöldebrand, Eva; Windahl, S; Junevik, K; Brisby, Helena

Abstract

Disk-degeneration is believed a major cause for lumbar pain. Previously, potential stem cell niches in the intervertebral disk (IVD) region, located adjacent to epiphyseal plate, was reported. The aim of the study was to examine migration of mesenchymal stem cells (MSCs), extracellular matrix (ECM) architecture in a potential cellular migration route (CMR; area located between the niche and IVD) and in the IVD in non-degenerated lapine- and in human degenerated IVD tissues. Human MSCs (n = 3), human degenerated IVD tissues (n = 10) and lapine IVDs (n = 10) were collected. The samples were examined by immunohistochemistry for stem cell markers; CD90, OCT3/4, pre-chondrocytic marker; GDF5, catabolic markers; MMP9, MMP13, inflammatory marker; IL1R, cellular migration markers; SNAIL SNAI2, adhesion markers; beta 1-INTEGRIN and DDR2. In addition, gene-expression analyses (Real time PCR) were performed on additional samples. Further, time lapse studies were performed with hMSCs cultured on aligned COLL-I-fibers-coated glass-slides in DMEM-LG, 10% human serum containing fibroblast growth factor (bFGF). Presence of stem cells (CD90+, OCT3/4(+)), pre-chondocytic cells (GDF5+) and cells positive for migration markers (SNAI1+, SNAI2+), catabolic markers (MMP9+, MMP13+), inflammatory marker (IL1R+), adhesion markers (DDR2+, B1-INTEGRIN+) were detected (gene- and protein level) in investigated CMR and IVD regions. In the time lapse studies, MSCs alignment and protrusions were observed orientated in the same direction as collagen fibers. Results display influence of ECM collagen architecture and collagen fiber spatial direction on migration of stem cells. The results can be useful when developing tissue-engineering strategies for disk-degeneration. (C) 2015 Elsevier Ltd. All rights reserved.

Keywords

Stem cell niche; Cellular migration; Collagen; Matrix metalloproteases; Extracellular matrix; Intervertebral disk

Published in

Tissue and Cell
2015, Volume: 47, number: 5, pages: 439-455
Publisher: CHURCHILL LIVINGSTONE

      SLU Authors

      • UKÄ Subject classification

      Cell Biology

      Publication identifier

      DOI: https://doi.org/10.1016/j.tice.2015.08.001

      Permanent link to this page (URI)

      https://res.slu.se/id/publ/75491