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Validation of iPS Cell-Derived RPE Tissue in Animal Models.
Adv Exp Med Biol. 2018; 1074:633-640.AE

Abstract

Previous work suggests that replacing diseased Retinal Pigment Epithelium (RPE) with a healthy autologous RPE sheet can provide vision rescue for AMD patients. We differentiated iPSCs into RPE using a directed differentiation protocol. RPE cells at the immature RPE stage were purified and seeded onto either electrospun poly(lactic-co-glycolic acid) (PLGA) scaffolds or non-biodegradable polyester cell culture inserts and compared the two tissues. In vitro, PLGA and polyester substrates produced functionally similar results. Following in vitro evaluation, we tested RPE tissue in animal models for safety and function. Safety studies were conducted in RNU rats using an injection composed of intact cells and homogenized scaffolds. To assess function and develop surgical procedures, the tissues were implanted into an acute RPE injury model pig eye and evaluated using optical coherence tomography (OCT), multifocal ERG (mfERG), and histology. Subretinal injection studies in rats demonstrated safety of the implant. Biodegradability and biocompatibility data from a pig model demonstrated that PLGA scaffold is safe, with the added benefit of being resorbed by the body over time, leaving no foreign material in the eye. We confirmed that biodegradable substrates provide suitable support for RPE maturation and transplantation.

Authors+Show Affiliations

Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, Bethesda, MD, USA. vladimir.khristov@gmail.com.Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, Bethesda, MD, USA.Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, Bethesda, MD, USA.Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, Bethesda, MD, USA.Unit on Ocular Stem Cell and Translational Research, National Eye Institute, Bethesda, MD, USA.Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, Bethesda, MD, USA.

Pub Type(s)

Journal Article
Validation Study

Language

eng

PubMed ID

29721997

Citation

Khristov, Vladimir, et al. "Validation of iPS Cell-Derived RPE Tissue in Animal Models." Advances in Experimental Medicine and Biology, vol. 1074, 2018, pp. 633-640.
Khristov V, Maminishkis A, Amaral J, et al. Validation of iPS Cell-Derived RPE Tissue in Animal Models. Adv Exp Med Biol. 2018;1074:633-640.
Khristov, V., Maminishkis, A., Amaral, J., Rising, A., Bharti, K., & Miller, S. (2018). Validation of iPS Cell-Derived RPE Tissue in Animal Models. Advances in Experimental Medicine and Biology, 1074, 633-640. https://doi.org/10.1007/978-3-319-75402-4_77
Khristov V, et al. Validation of iPS Cell-Derived RPE Tissue in Animal Models. Adv Exp Med Biol. 2018;1074:633-640. PubMed PMID: 29721997.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Validation of iPS Cell-Derived RPE Tissue in Animal Models. AU - Khristov,Vladimir, AU - Maminishkis,Arvydas, AU - Amaral,Juan, AU - Rising,Aaron, AU - Bharti,Kapil, AU - Miller,Sheldon, PY - 2018/5/4/entrez PY - 2018/5/4/pubmed PY - 2019/5/7/medline KW - AMD KW - Animal Models KW - Autologous KW - Biodegradable KW - RPE KW - Transplantation KW - iPSC SP - 633 EP - 640 JF - Advances in experimental medicine and biology JO - Adv Exp Med Biol VL - 1074 N2 - Previous work suggests that replacing diseased Retinal Pigment Epithelium (RPE) with a healthy autologous RPE sheet can provide vision rescue for AMD patients. We differentiated iPSCs into RPE using a directed differentiation protocol. RPE cells at the immature RPE stage were purified and seeded onto either electrospun poly(lactic-co-glycolic acid) (PLGA) scaffolds or non-biodegradable polyester cell culture inserts and compared the two tissues. In vitro, PLGA and polyester substrates produced functionally similar results. Following in vitro evaluation, we tested RPE tissue in animal models for safety and function. Safety studies were conducted in RNU rats using an injection composed of intact cells and homogenized scaffolds. To assess function and develop surgical procedures, the tissues were implanted into an acute RPE injury model pig eye and evaluated using optical coherence tomography (OCT), multifocal ERG (mfERG), and histology. Subretinal injection studies in rats demonstrated safety of the implant. Biodegradability and biocompatibility data from a pig model demonstrated that PLGA scaffold is safe, with the added benefit of being resorbed by the body over time, leaving no foreign material in the eye. We confirmed that biodegradable substrates provide suitable support for RPE maturation and transplantation. SN - 0065-2598 UR - https://www.unboundmedicine.com/medline/citation/29721997/Validation_of_iPS_Cell_Derived_RPE_Tissue_in_Animal_Models_ L2 - https://dx.doi.org/10.1007/978-3-319-75402-4_77 DB - PRIME DP - Unbound Medicine ER -