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First published online October 19, 2006
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2006-0308v1
25/3/602    most recent
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Submitted on May 23, 2006
Accepted on October 13, 2006

Tissue-Specific Stem Cells

Cells isolated from umbilical cord tissue rescue photoreceptors and visual functions in a rodent model of retinal disease

Raymond D. Lund 1, Shaomei Wang 1, Bin Lu 1, Sergej Girman 1, Toby Holmes 2, Yves Sauvé 3, Darin J. Messina 4, Ian R. Harris 4, Tony J. Kihm 5, Alex M. Harmon 5, Chin Feng-Yi 5, Anna Gosiewska 5, Sanjay K. Mistry 4*

1 Moran Eye Center, University of Utah Health Science Center, Salt Lake City, Utah; Eye Institute, Oregon Health & Sciences University, Portland, Oregon
2 Moran Eye Center, University of Utah Health Science Center, Salt Lake City, Utah
3 Ophthalmology and Physiology, University of Alberta, Edmonton, Alberta, Canada
4 Centocor, Johnson & Johnson Internal Ventures, Radnor, Pennsylvania
5 Ethicon Inc., Center for Biomaterials and Advanced Technologies, Somerville, New Jersey

* To whom correspondence should be addressed. E-mail: smistry5{at}cntus.jnj.com.


  Abstract

Progressive photoreceptor degeneration resulting from genetic and other factors is a leading and largely untreatable cause of blindness worldwide. The object of this study was to find a cell type that is effective in slowing the progress of such degeneration in an animal model of human retinal disease, is safe and could be generated in sufficient numbers for clinical application. We have compared efficacy of four human-derived cell types in preserving photoreceptor integrity and visual functions after injection into the subretinal space of the Royal College of Surgeons rat early in the progress of degeneration. Umbilical tissue-derived cells, placenta-derived cells, and mesenchymal stem cells were studied; dermal fibroblasts served as cell controls. At various ages up to 100 days, electroretinogram responses, spatial acuity and luminance threshold were measured. Both umbilical-derived and mesenchymal cells significantly reduced the degree of functional deterioration in each test. The effect of placental cells was little better than controls. Umbilical tissue-derived cells gave large areas of photoreceptor rescue; mesenchymal stem cells gave only localized rescue. Fibroblasts gave sham levels of rescue. Donor cells were confined to the subretinal space. There was no evidence of cell differentiation into neurons, of tumor formation or other untoward pathology. Since the umbilical tissue-derived cells demonstrated the best photoreceptor rescue and unlike mesenchymal stem cells were capable of sustained population doublings without karyotypic changes, it is proposed that they may provide utility as a cell source for the treatment of retinal degenerative diseases such as retinitis pigmentosa.

Key Words. Retinal disease, cell-based therapy, RCS rat, umbilical cord, visual function, photoreceptor




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