title: The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the recruitment of MSCs in degenerating intervertebral discs.
abstract: Intervertebral disc (IVD) degeneration is the leading cause of low back pain and disability in the active population. Transplantation of mesenchymal stem cells (MSCs) in a hydrogel carrier can induce regenerative effects in degenerated IVDs. Moreover, it was found that degenerative discs release chemoattractants effective in MSC recruitment. Based on these findings, we hypothesized that an injectable hydrogel that can enhance the number of migrated MSCs in the IVD and provide a suitable matrix for their survival and differentiation would be ideal. The purpose of this study was to evaluate the potential of a thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel as chemoattractant delivery system to recruit human MSCs in degenerative IVDs. The results demonstrate that HAP hydrogels containing stromal cell derived factor-1 (SDF-1) significantly increased the number of MSCs migrating into nucleotomized discs compared with discs treated with only HAP or SDF-1 in solution. HAP hydrogels releasing SDF-1 enhanced both the number of recruited cells and their migration distance in the IVD tissue. Furthermore, this phenomenon was dependent on MSC donor age. In conclusion, HAP SDF-1 is effective for the recruitment of stem cells in the IVD, thus opening new possibilities for the development of regenerative therapies based on endogenous cell migration.
authors: INEB - Instituto de Engenharia Biomédica, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors: Catarina Leite
authors: CL
authors: Pereira
authors: INEB - Instituto de Engenharia Biomédica, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
authors: Raquel M
authors: RM
authors: Gonçalves
authors: AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland.
authors: Marianna
authors: M
authors: Peroglio
authors: AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland.
authors: Girish
authors: G
authors: Pattappa
authors: AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland.
authors: Matteo
authors: M
authors: D'Este
authors: AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland.
authors: David
authors: D
authors: Eglin
authors: INEB - Instituto de Engenharia Biomédica, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors: Mário A
authors: MA
authors: Barbosa
authors: AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland.
authors: Mauro
authors: M
authors: Alini
authors: AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland. Electronic address: sibylle.grad@aofoundation.org.
authors: Sibylle
authors: S
authors: Grad
mesh_terms: D020106:Acrylamide / Q000737:chemistry; D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002356:Cartilage / Q000473:pathology; D002417:Cattle; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002630:Chemotactic Factors / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry; D007150:Immunohistochemistry; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010641:Phenotype
chemical_list: D000178:Acrylamides; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D002630:Chemotactic Factors; D020100:Hydrogels; D020106:Acrylamide; D006820:Hyaluronic Acid
keywords: Intervertebral disc; Mesenchymal stem cells; Recruitment; Stromal cell derived factor-1; Thermoreversible hyaluronan hydrogel