Long-Term Safety and Function of RPE-Free-Samples for Students

Question: Discuss about the Annotated bibliography of Long-term safety and function of RPE from Human Embryonic Stem Cells in preclinical Models of Macular degeneration. Answer: Citation: Lu, B., Malcuit, C., Wang, S., Girman, S., Francis, P., Lemieux, L., Lanza, R. and Lund, R., 2009. Long?term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration.Stem cells,27(9), pp.2126-2135. Introduction: Human ESCs are considered as a key resource of clinical studies, for replacing cells. Prior the further advancement of somatic cell nuclear transfer or induced pluripotent stem cell technology in the clinical field, eye diseases is the first hESC-derived therapies. Compromised function of retinal pigment epithelial cell may lead to deteriorated vision and photoreceptor loss in retinitis pigmentosa and age-related macular degeneration. Instead of the fact that there is limited treatment options, implantation of RPE cells have shown sustained photoreceptor and control deterioration of visual function has been evident in animal model. Here authors used previously published RPE-derivation protocols for showing long-term functions using hESC-derived RPE in animal models of retinal degeration and stargardt. According to the protocol, authors attempted to prepare for clinical application and testing for safety and efficacy in several different animal and in vitro models. Authors also investigated if vision can be rescued in the mouse model used for the STGD disease, which is an early form of macular dystrophy. Methodology: 79 pigmented dystrophic RCS rats and 28 ELOVL4 mice were used for the main experiment, whereas 45 NIH III immune nude mice were used for safety study. Experiments were done according to the guidelines provided by the NIH regarding the care and animal model for experimental procedures and ARVO statement for using animals in Ophthalmic and vision research. According to the doses, the mice group received, these were divided into five groups. Two groups were added for further comparison, with two different dosages. The experimental and control group animals were maintained under 12 hour light/dark cycle. Authors performed a Real time PCR with the extracted RNA from the differentiated hESC cells into Mature RPE cells. For gene profiling, microarray and western blot analysis was done. Then transplantation, spatial visual acuity and luminance thresholds were also measures. Results: The differentiated cells survived the transplantation in RCS rats for a long period and sustained the visual function. Cells also sustained the receptor integrity in a dose-dependent manner. At 60 says survival in RCS rats, near normal functional measurements were observed. Long term data did not reveal gross or microscopic evidence of tumor formation after transplantation, suggesting that the cell line can be used as safe and inexhaustible source of RPE for retinal degenerative diseases treatment. In the safety assessment done with NIH III mice, the formation of teratoma and retention of pigmentation was observed among the safety study group mice, i.e. NIH III mice. In contrast, in the RCS rat transplant study, no evidence off teratoma or uncontrolled cell proliferation was found. Conclusions: The authors represented that the long-term safety and efficacy of hESC derived RPE cells can be used for human clinical trials, under the manufacturing conditions these have been produced. In order to confirm the functionality of these cells, the dose response was also evaluated besides the long term efficacy of the cell line. The study showed that hESC-derived RPE cells in immune-deficient animal represent a long-term function and safety in two animal models, highlighting its potential use in clinical therapies for specific macular degenerative diseases. Limitations: A requirement for identifying whether some kinds of immunosuppression is needed, during the use of cells in clinical settings was there, which has not been explored by the author. Reflection: In this current article, author provided significant information and evidence for the usage of hESCs as clinically potential cell line for treating macular degenerative diseases. The article has been published in 2009 and it has been used in other further research in this domain, which represents its potentiality in research field Reference List Lu, B., Malcuit, C., Wang, S., Girman, S., Francis, P., Lemieux, L., Lanza, R. and Lund, R., 2009. Long?term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration.Stem cells,27(9), pp.2126-2135. Schwartz, S.D., Regillo, C.D., Lam, B.L., Eliott, D., Rosenfeld, P.J., Gregori, N.Z., Hubschman, J.P., Davis, J.L., Heilwell, G., Spirn, M. and Maguire, J., 2015. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies.The Lancet,385(9967), pp.509-516.