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Validation of iPS Cell-Derived RPE Tissue in Animal Models

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1074))

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.

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Acknowledgments

We would like to thank Dr. Mones Abu-Asab of the NEI histology core for TEM image contributions. We would also like to thank the unwavering commitment of the animal care teams at NEI that made this research possible.

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Authors and Affiliations

  1. Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, Bethesda, MD, USA

    Vladimir Khristov, Arvydas Maminishkis, Aaron Rising & Sheldon Miller

  2. Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, Bethesda, MD, USA

    Juan Amaral

  3. Unit on Ocular Stem Cell and Translational Research, National Eye Institute, Bethesda, MD, USA

    Kapil Bharti

Authors
  1. Vladimir Khristov
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  2. Arvydas Maminishkis
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  3. Juan Amaral
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  4. Aaron Rising
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  5. Kapil Bharti
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  6. Sheldon Miller
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Corresponding author

Correspondence to Vladimir Khristov .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. Ophthalmology and Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  3. School of Medicine Beckman Vision Center, University of California San Francisco, San Francisco, California, USA

    Matthew M. LaVail

  4. Departments of Ophthalmology and Cell Biology, Duke Eye Center, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

  5. Division of Ophthalmology, Case Western Reserve University, Cleveland, Ohio, USA

    Joe G. Hollyfield

  6. Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

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© 2018 Springer International Publishing AG, part of Springer Nature

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Khristov, V., Maminishkis, A., Amaral, J., Rising, A., Bharti, K., Miller, S. (2018). Validation of iPS Cell-Derived RPE Tissue in Animal Models. In: Ash, J., Anderson, R., LaVail, M., Bowes Rickman, C., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1074. Springer, Cham. https://doi.org/10.1007/978-3-319-75402-4_77

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