Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.

Hongshan Liu,Martin Sieber,Winston W Y Kao,Chia-Yang Liu,I-Jong Wang,Jianhua Zhang,James V Jester,John Chang,Che John Connon

doi:10.1371/journal.pone.0010707

Abstract

BackgroundKeratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation.Methodology/Principal FindingsHuman mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice.Conclusions/SignificanceUmbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need.

Highlights

There are growing interests in the use of stem cells, e.g., embryonic stem cells, mesenchymal stem cells, hematopoietic stem cells, etc. in treating human congenital diseases caused by genetic mutation and acquired diseases [1,2,3,4,5,6,7,8]
Characteristics of Umbilical cordderived mesenchymal stem cells (UMSCs) isolated from human umbilical cord
The results showed that .95% of the fibroblast-like plastic-adherent cells expressed characteristic CD markers of mesenchymal stem cells, e.g., CD105/SH2, CD73/SH3 (NT5E), CD90 (Thy1), CD29, CD44 (HA receptor), CD13; and,1% of cells were positive for hematopoietic cell CD markers, e.g., CD45, CD34, CD14, HLA-DR (MHC-II), and CD31 (Fig. 1A)

Summary

Introduction

There are growing interests in the use of stem cells, e.g., embryonic stem cells, mesenchymal stem cells, hematopoietic stem cells, etc. in treating human congenital diseases caused by genetic mutation and acquired diseases [1,2,3,4,5,6,7,8]. Since mesenchymal stem cells (MSCs) are first isolated from bone marrow, these plastic adherent cells have been identified and cultivated from many connective tissues, e.g., umbilical cord, amniotic membrane, cartilage, adipose tissue, and conjunctiva [11,12,13,14]. Umbilical cordderived mesenchymal stem cells (UMSCs) from newborns are presumably young and are likely to have a more potent proliferation and differentiation capability. The utilization of human UMSCs in treating disease is surprisingly rare in comparison to the use of bone marrow MSCs. Only a limited number of publications have reported on the success of using human UMSCs to treat liver fibrosis and spinal cord injury in animal models [24,25,26,27]. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation

Methods

Results

Conclusion