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Retinal Progenitor Cell Xenografts to the Pig Retina
Morphologic Integration and Cytochemical Differentiation
Karin Warfvinge, PhD;
Jens F. Kiilgaard, MD, PhD;
Erin B. Lavik, DSc;
Erik Scherfig, MD;
Robert Langer, PhD;
Henry J. Klassen, MD, PhD;
Michael J. Young, PhD
Arch Ophthalmol. 2005;123:1385-1393.
Objective: To investigate the survival, integration, and differentiation of mouse retinal progenitor cells after transplantation to the subretinal space of adult pigs.
Methods: Green fluorescent protein–positive (GFP+) murine retinal progenitor cells were transplanted subretinally as single cells, spheres, or biodegradable polymer-progenitor composites into 24 nonimmunosuppressed adult pigs. Of these, 14 pigs received laser lesions (n = 11) or outer retinal scraping injury (n = 3). Recipients were killed at 30 minutes to 5 weeks after grafting.
Results The GFP+ murine retinal progenitor cells survived well for up to 14 days after transplantation to the pig retina. After 5 weeks, fewer GFP+ cells were found. In the pigs that received laser treatment before grafting of cell suspension, GFP+ cells integrated into the retinal pigment epithelium and all layers of the retina. The GFP+ cells exhibited morphologic evidence of differentiation into mature retinal neurons, although evaluation of marker expression found only nestin and glial fibrillary acidic protein colocalization. In noninjured pigs, cells mainly integrated into the retinal pigment epithelium. In pigs that received composites, cells appeared to mature and extended processes through pores in the polymer matrix.
Conclusions Retinal progenitor cell xenografts survive for a sufficiently long period to integrate into areas of injury and exhibit morphologic differentiation. By 5 weeks, survival diminishes. Biodegradable polymers may be useful for transplanting retinal progenitor cells in a structurally organized manner.
Clinical Relevance Central nervous system (CNS) diseases may cause long-term disabilities. Substantial tissue destruction can be sustained by the complex structures of the brain, spinal cord, or retina without loss of life, yet the lack of effective CNS regeneration frequently results in disruption of activities of daily living and marked degradation in quality of life. It has become clear that an enormous potential for repair is present within the mammalian CNS. The challenge is to harness this potential to treat disease. Transplantation of neuronal tissue to the CNS represents a promising, albeit challenging, approach to the replacement of neurons lost owing to injury or disease.
Author Affiliations: Department of Ophthalmology, Lund University Hospital, Lund, Sweden (Dr Warfvinge); Eye Department, Rigshospitalet and Eye Pathology Institute, Copenhagen University, Copenhagen, Denmark (Drs Kiilgaard and Scherfig); Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Mass (Drs Lavik and Langer); Stem Cell Research, Children’s Hospital of Orange County, Orange, Calif (Dr Klassen); and Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Mass (Dr Young).
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