Indications of that migration of stem cells is influenced by the extra cellular matrix architecture in the mammalian intervertebral disk region.
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; SNAI1, SNAI2, adhesion markers; β1-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.
Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Orthopaedics, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: helena.barreto.henriksson@gu.se.
H Barreto
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Henriksson
Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Orthopaedics, Sahlgrenska University Hospital, Gothenburg, Sweden.
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Papadimitriou
Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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Tschernitz
Department of Clinical Chemistry and Transfusion medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
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Svala
Department of Clinical Chemistry and Transfusion medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
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Skioldebrand
Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Centre for Comparative and Clinical Anatomy, School of Veterinary Science, University of Bristol, Bristol, United Kingdom.
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Windahl
Department of Clinical Chemistry and Transfusion medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
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Junevik
Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Orthopaedics, Sahlgrenska University Hospital, Gothenburg, Sweden.
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Brisby
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006132:Growth Plate / Q000378:metabolism; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D017116:Low Back Pain / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011817:Rabbits
D015415:Biomarkers
Cellular migration; Collagen; Extracellular matrix; Intervertebral disk; Matrix metalloproteases; Stem cell niche