Genetic Engineering of Mesenchymal Stem Cells for Differential Matrix Deposition on 3D Woven Scaffolds.

Published

Journal Article

Tissue engineering approaches for the repair of osteochondral defects using biomaterial scaffolds and stem cells have remained challenging due to the inherent complexities of inducing cartilage-like matrix and bone-like matrix within the same local environment. Members of the transforming growth factor β (TGFβ) family have been extensively utilized in the engineering of skeletal tissues, but have distinct effects on chondrogenic and osteogenic differentiation of progenitor cells. The goal of this study was to develop a method to direct human bone marrow-derived mesenchymal stem cells (MSCs) to deposit either mineralized matrix or a cartilaginous matrix rich in glycosaminoglycan and type II collagen within the same biochemical environment. This differential induction was performed by culturing cells on engineered three-dimensionally woven poly(ɛ-caprolactone) (PCL) scaffolds in a chondrogenic environment for cartilage-like matrix production while inhibiting TGFβ3 signaling through Mothers against DPP homolog 3 (SMAD3) knockdown, in combination with overexpressing RUNX2, to achieve mineralization. The highest levels of mineral deposition and alkaline phosphatase activity were observed on scaffolds with genetically engineered MSCs and exhibited a synergistic effect in response to SMAD3 knockdown and RUNX2 expression. Meanwhile, unmodified MSCs on PCL scaffolds exhibited accumulation of an extracellular matrix rich in glycosaminoglycan and type II collagen in the same biochemical environment. This ability to derive differential matrix deposition in a single culture condition opens new avenues for developing complex tissue replacements for chondral or osteochondral defects.

Full Text

Duke Authors

Cited Authors

  • Huynh, NPT; Brunger, JM; Gloss, CC; Moutos, FT; Gersbach, CA; Guilak, F

Published Date

  • October 2018

Published In

Volume / Issue

  • 24 / 19-20

Start / End Page

  • 1531 - 1544

PubMed ID

  • 29756533

Pubmed Central ID

  • 29756533

Electronic International Standard Serial Number (EISSN)

  • 1937-335X

International Standard Serial Number (ISSN)

  • 1937-3341

Digital Object Identifier (DOI)

  • 10.1089/ten.tea.2017.0510

Language

  • eng