title: Effect of transforming growth factor-beta and growth differentiation factor-5 on proliferation and matrix production by human bone marrow stromal cells cultured on braided poly lactic-co-glycolic acid scaffolds for ligament tissue engineering.
abstract: Tissue engineering of ligaments based on biomechanically suitable biomaterials combined with autologous cells may provide a solution for the drawbacks associated with conventional graft material. The aim of the present study was to investigate the contribution of recombinant human transforming growth factor beta 1 (rhTGF-beta1) and growth differentiation factor (GDF)-5, known for their role in connective tissue regeneration, to proliferation and matrix production by human bone marrow stromal cells (BMSCs) cultured onto woven, bioabsorbable, 3-dimensional (3D) poly(lactic-co-glycolic acid) scaffolds. Cells were cultured for 12 days in the presence or absence of these growth factors at different concentrations. Human BMSCs attached to the suture material, proliferated, and synthesized extracellular matrix rich in collagen type I and collagen III. No differentiation was demonstrated toward cartilage or bone tissue. The addition of rhTGF-beta1 (1-10 ng/mL) and GDF-5 (10-100 ng/mL) increased cell content (p < 0.05), but only TGF-beta1 also increased total collagen production (p < 0.05) and collagen production per cell, which is a parameter indicating differentiation. In conclusion, stimulation with rhTGF-beta1, and to a lesser extent with GDF-5, can modulate human BMSCs toward collagenous soft tissue when applied to a 3D hybrid construct. The use of growth factors could play an important role in the improvement of ligament tissue engineering.
authors.affiliation: Department of Orthopedics, University Medical Center, Utrecht, The Netherlands.
authors.forename: J M G Th
authors.initials: JM
authors.lastname: Jenner
authors.forename: F
authors.initials: F
authors.lastname: van Eijk
authors.forename: D B F
authors.initials: DB
authors.lastname: Saris
authors.forename: W J
authors.initials: WJ
authors.lastname: Willems
authors.forename: W J A
authors.initials: WJ
authors.lastname: Dhert
authors.forename: Laura B
authors.initials: LB
authors.lastname: Creemers
mesh_terms: D001854:Bone Marrow Cells / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D055428:Growth Differentiation Factor 5; D006801:Humans; D019344:Lactic Acid; D008022:Ligaments; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D017154:Stromal Cells / Q000378:metabolism; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; D011108:Polymers; D016212:Transforming Growth Factor beta; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid