title: Mesenchymal Stem/Stromal Cells seeded on cartilaginous endplates promote Intervertebral Disc Regeneration through Extracellular Matrix Remodeling.
abstract: 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.
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, 4050-313, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.|INEB, Instituto de Engenharia Biomédica, Universidade do Porto, Porto, 4200-135, Portugal.
authors.forename: Catarina Leite
authors.initials: CL
authors.lastname: Pereira
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, 4050-313, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.|INEB, Instituto de Engenharia Biomédica, Universidade do Porto, Porto, 4200-135, Portugal.
authors.forename: Graciosa Q
authors.initials: GQ
authors.lastname: Teixeira
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.|INEB, Instituto de Engenharia Biomédica, Universidade do Porto, Porto, 4200-135, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Ribeiro-Machado
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.|INEB, Instituto de Engenharia Biomédica, Universidade do Porto, Porto, 4200-135, Portugal.|IPATIMUP-Institute of molecular pathology and immunology of the university of Porto, Porto 4200-135, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Caldeira
authors.affiliation: UMIB-Unit for Multidisciplinary Biomedical Research of ICBAS, Universidade do Porto, Porto, 4050-313, Portugal.
authors.forename: Madalena
authors.initials: M
authors.lastname: Costa
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.|IBMC-Instituto de Biologia Molecular e Celular, Porto 4150-180, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Figueiredo
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.|IBMC-Instituto de Biologia Molecular e Celular, Porto 4150-180, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Fernandes
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.|INEB, Instituto de Engenharia Biomédica, Universidade do Porto, Porto, 4200-135, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Aguiar
authors.affiliation: AO Research Institute Davos, Davos, 7270, Switzerland.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Grad
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, 4050-313, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.|INEB, Instituto de Engenharia Biomédica, Universidade do Porto, Porto, 4200-135, Portugal.
authors.forename: Mário A
authors.initials: MA
authors.lastname: Barbosa
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.|INEB, Instituto de Engenharia Biomédica, Universidade do Porto, Porto, 4200-135, Portugal.
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Gonçalves