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-β1. After 4 weeks, the mean thickness of the constructs was ∼30 μm; 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-β1. Keratocan on the other hand decreased with TGF-β1 in both cell lineages. With both cell types, the constructs possessed aligned collagen fibrils and associated glycosaminoglycans. Fibril diameters did not change with TGF-β1 stimulation or cell lineage; however, highly sulfated glycosaminoglycans associated with the collagen fibrils significantly increased with TGF-β1. 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.

Highlights

  • One of the main threats for the human eye following injury or disease is the development of a scar, which can compromise a person’s vision and even lead to blindness

  • We examined the ability of cord stem cells to synthesize a matrix in the presence of Vitamin C (VitC) ± TGF- 1

  • After 4 weeks, cord stem cells cultured in the presence of VitC resulted in a construct approximately 35 m thick, which is similar to constructs synthesized by human corneal fibroblasts under the same conditions (Figure 1.1 and 1.2A, C) [21,22]

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Summary

Introduction

One of the main threats for the human eye following injury or disease is the development of a scar, which can compromise a person’s vision and even lead to blindness. Treatment options are generally limited to corneal transplants, several investigations have examined the potential use of biomaterials as a corneal substitute. Studies have considered the possibility of stem cell transplantation. Stem cells have the potential to repair damaged organs and tissues, and they are known for their unique intrinsic characteristics, which enable them to control cell replacement during homeostasis and tissue repair [1]. The characteristics of stem cells make them highly attractive for use in tissue engineering and artificial in vitro applications. The most commonly used source of adult mesenchymal stem cells (MSCs) is the bone marrow (BMSCs); MSCs are found in adipose tissue, blood, dermis and fat

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