Open AccessMesenchymal Stem/Stromal Cells seeded on cartilaginous endplates promote Intervertebral Disc Regeneration through Extracellular Matrix Remodeling
Author(s) -
Catarina Leite Pereira,
Graciosa Q. Teixeira,
Cláudia Ribeiro-Machado,
Joana Caldeira,
María Teresa Costa,
Francisco Figueiredo,
Rui Fernandes,
Paulo Aguiar,
Sibylle Grad,
Mário A. Barbosa,
Raquel M. Gonçalves
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep33836
Subject(s) - mesenchymal stem cell , aggrecan , microbiology and biotechnology , extracellular matrix , regeneration (biology) , intervertebral disc , aggrecanase , growth factor , fibroblast growth factor , stromal cell , biology , chemistry , pathology , anatomy , cancer research , medicine , receptor , osteoarthritis , biochemistry , alternative medicine , articular cartilage
Intervertebral disc (IVD) degeneration is characterized by significant biochemical and histomorphological alterations, such as loss of extracellular matrix (ECM) integrity, by abnormal synthesis of ECM main components, resultant from altered anabolic/catabolic cell activities and cell death. Mesenchymal Stem/Stromal Cell (MSC) migration towards degenerated IVD may represent a viable strategy to promote tissue repair/regeneration. Here, human MSCs (hMSCs) were seeded on top of cartilaginous endplates (CEP) of nucleotomized IVDs of bovine origin and cultured ex vivo up to 3 weeks. hMSCs migrated from CEP towards the lesion area and significantly increased expression of collagen type II and aggrecan in IVD, namely in the nucleus pulposus. Concomitantly, hMSCs stimulated the production of growth factors, promoters of ECM synthesis, such as fibroblast growth factor 6 (FGF-6) and 7 (FGF-7), platelet-derived growth factor receptor (PDGF-R), granulocyte-macrophage colony-stimulating factor (GM-CSF) and insulin-like growth factor 1 receptor (IGF-1sR). Overall, our results demonstrate that CEP can be an alternative route to MSC-based therapies for IVD regeneration through ECM remodeling, thus opening new perspectives on endogenous repair capacity through MSC recruitment.