title: Self-assembled matrix by umbilical cord stem cells.
abstract: Corneal integrity is critical for vision. Corneal wounds frequently heal with scarring that impairs vision. Recently, human umbilical cord mesenchymal stem cells (cord stem cells) have been investigated for tissue engineering and therapy due to their availability and differentiation potential. In this study, we used cord stem cells in a 3-dimensional (3D) stroma-like model to observe extracellular matrix organization, with human corneal fibroblasts acting as a control. For 4 weeks, the cells were stimulated with a stable Vitamin C (VitC) derivative ±TGF-b1. After 4 weeks, the mean thickness of the constructs was ~30 mm; however, cord stem cell constructs had 50% less cells per unit volume, indicating the formation of a dense matrix. We found minimal change in decorin and lumican mRNA, and a significant increase in perlecan mRNA in the presence of TGF-b1. Keratocan on the other hand decreased with TGF-b1 in both cell lineages. With both cell types, the constructs possessed aligned collagen fibrils and associated glycosaminoglycans. Fibril diameters did not change with TGF-b1 stimulation or cell lineage; however, highly sulfated glycosaminoglycans associated with the collagen fibrils significantly increased with TGF-b1. Overall, we have shown that cord stem cells can secrete their own extracellular matrix and promote the deposition and sulfation of various proteoglycans. Furthermore, these cells are at least comparable to commonly used corneal fibroblasts and present an alternative for the 3D in vitro tissue engineered model.
authors: Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston MA 02114, USA. dimitris.karamichos@schepens.harvard.edu.
authors: Dimitrios
authors: D
authors: Karamichos
authors: Department of Biochemistry, Boston University School of Medicine, 80 E Concord Street, Boston, MA 02118, USA. cbrich@bu.edu.
authors: Celeste B
authors: CB
authors: Rich
authors: Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston MA 02114, USA. audrey.hutcheon@schepens.harvard.edu.
authors: Audrey E K
authors: AE
authors: Hutcheon
authors: Department of Biochemistry, Boston University School of Medicine, 80 E Concord Street, Boston, MA 02118, USA. renruiyi@bu.edu.
authors: Ruiyi
authors: R
authors: Ren
authors: Department of Biomedical Sciences, Medical Genetics and Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8727 W. Third Street, Metro Building, Suite 203, Los Angeles, CA 90048, USA. saittabiagio@gmail.com.
authors: Biagio
authors: B
authors: Saitta
authors: Department of Biochemistry, Boston University School of Medicine, 80 E Concord Street, Boston, MA 02118, USA. vickery@bu.edu.
authors: Vickery
authors: V
authors: Trinkaus-Randall
authors: Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston MA 02114, USA. james.zieske@schepens.harvard.edu.
authors: James D
authors: JD
authors: Zieske