June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Hypo-immunogenic Human Umbilical Cord Lining derived Retinal Pigment Epithelial (CLiPS-RPE) Monolayers for Treatment of Atrophic Maculopathies
Author Affiliations & Notes
  • Xinyi Su
    Ophthalmology, National University of Singapore, Singapore, Singapore
    Institute of Molecular and Cell Biology, Singapore, Singapore
  • Bhav Harshad Parikh
    Institute of Molecular and Cell Biology, Singapore, Singapore
  • Qing Feng Chen
    Institute of Molecular and Cell Biology, Singapore, Singapore
  • Zengping Liu
    Ophthalmology, National University of Singapore, Singapore, Singapore
  • Veluchamy Barathi
    Singapore Eye Research Institute, Singapore, Singapore
    Ophthalmology, National University of Singapore, Singapore, Singapore
  • Kah Leong Lim
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore, Singapore
  • Footnotes
    Commercial Relationships   Xinyi Su None; Bhav Parikh None; Qing Feng Chen None; Zengping Liu None; Veluchamy Barathi None; Kah Leong Lim None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4615. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Xinyi Su, Bhav Harshad Parikh, Qing Feng Chen, Zengping Liu, Veluchamy Barathi, Kah Leong Lim; Hypo-immunogenic Human Umbilical Cord Lining derived Retinal Pigment Epithelial (CLiPS-RPE) Monolayers for Treatment of Atrophic Maculopathies. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4615.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Transplantation of stem cell derived RPE cells is a viable therapeutic option for atrophic maculopathies. However, its efficacy is limited by localized inflammatory response and immune-rejection. Umbilical cord lining tissue has gained interest as a universal cell source due to the presence of young, immunologically naïve epithelial stem cells. In this study, we reprogrammed cord lining epithelial cells into iPSC (CLiPS) and postulated that CLiPS-RPE will retain “immuno-privileged” properties inherent to the maternal-fetal interface through epigenetic memory.

Methods : CLiPS cells were differentiated into RPE and matured in-vitro on transwells. CLiPS-RPE were trephined to form 1x2 mm bullet shaped implants and transplanted into sub-retinal space of 9 immunocompetent monkeys (Macaca fascicularis) to assess for survival and engraftment. Multimodal imaging including optical coherence tomography (OCT) was conducted for 2 months. CLiPS-RPE were transplanted subcutaneously into mice models reconstituted with functional human immune system and immune-deficient control NOD-SCID IL2Ry-/- (NSG) to assess for cell survival and induction of immune-response.

Results : t 2-month post-implantation, all iPSC-RPE monolayers (n=10) remained at original placement site within the macula. CLiPS-RPE grafts demonstrated preservation of the outer nuclear layer and ellipsoid zone (EZ) on OCT in 75.0% of eyes (n=4). In contrast, skin-iPSC-RPE monolayers demonstrated a loss of EZ, with intra-retinal infiltration in 83.3% of eyes (n=6). CLiPS-RPE and skin-iPSC-RPE cells transplanted into subcutaneous space of immuno-competent humanized mice survived for 2-months on histology. However, there was an absence of human hCD45 immune cell infiltration in CLiPS-RPE injected humanized mice, but not in skin-iPSC RPE injected controls. In addition, systemic serum pro-inflammatory cytokines were induced only in skin-iPSC-RPE injected humanized mice (IFN-γ: p=0.005; IL-18: p=0.111), but not in CLiPS-RPE injected mice (IFN-γ: p=0.212; IL-18: p>0.999).

Conclusions : Our findings demonstrate that CLiPS-RPE exhibits hypo-immunogenic properties in both immunocompetent non-human primate and mice models. It has the potential to serve as a genetically unmodified, somatically pristine and universal “off-the-shelf” cell resource for treatment of atrophic maculopathies.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×