Neurally selected embryonic stem cells induce tumor formation after long-term survival following engraftment into the subretinal space.
OBJECTIVE
To determine whether transplantation of embryonic stem (ES) cells into the subretinal space of rhodopsin-knockout mice has a tumorigenic effect.


METHODS
Mouse ES-cell-derived neural precursor cells carrying the sequence for the green fluorescent protein (GFP) gene were grafted subretinally into the eyes of rhodopsin(-/-) mice, whereas control animals underwent sham surgery. Eyes were retrieved after 2, 4, and 8 weeks after cell injection or sham surgery for histologic analysis.


RESULTS
Gross morphologic, histologic, and immunohistochemical analysis of eyes at 2 and 4 weeks after engraftment exhibited no morphologic alterations, whereas neoplasia formation was detected in 50% of the eyes evaluated at 8 weeks after engraftment. Because the neoplasias expressed differentiation characteristics of the different germ layers, they were considered to be teratomas. The resultant tumor formation affected almost all layers of the eye, including the retina, the vitreous, and the choroid.


CONCLUSIONS
Although ES cells may provide treatment for degenerative disease in the future, their unlimited self-renewal and high differentiation potential poses the risk of tumor induction after engraftment. Thus, more care must be taken before using ES cell transplantation as a therapeutic option for patients with degenerative disease.
Arnhold
Stefan
S
Department of Anatomy I, University of Cologne, Cologne, Joseph-Stelzmann Strasse 9, 50931 Köln, Germany. stefan.arnhold@uni-koeln.de
Klein
Helmut
H
Semkova
Irina
I
Addicks
Klaus
K
Schraermeyer
Ulrich
U
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D005134:Eye Neoplasms / Q000209:etiology* / Q000473:pathology; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry / Q000379:methods; D007267:Injections; D049408:Luminescent Agents; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000637:transplantation; D012160:Retina / Q000601:surgery*; D012243:Rhodopsin / Q000172:deficiency; D013194:Staining and Labeling; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013234:Stem Cells / Q000166:cytology; D013724:Teratoma / Q000209:etiology* / Q000473:pathology; D013997:Time Factors
D049408:Luminescent Agents; D049452:Green Fluorescent Proteins; D012243:Rhodopsin