June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Human iPSC derived CD34+ cells and endothelial colony-forming cells (ECFCs) correct diabetic retinopathy (DR) in a model of type 2 diabetes
Author Affiliations & Notes
  • Yazen Shihab
    Ophthalmology and Visual Science, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Sergio Li Calzi
    Ophthalmology and Visual Science, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Yvonne Adu-Agyeiwaah
    Ophthalmology and Visual Science, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Cristiano Vieira
    Ophthalmology and Visual Science, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Michael E. Boulton
    Ophthalmology and Visual Science, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Carolina Francelin Rovarotto
    Ophthalmology and Visual Science, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Matt George
    Vascugen, Inc., Indiana University, Madison, Wisconsin, United States
  • Dave Mann
    Vascugen, Inc., Indiana University, Madison, Wisconsin, United States
  • Mervin C. Yoder
    Indiana Center for Regenerative Medicine and Engineering, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Maria B Grant
    Ophthalmology and Visual Science, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Yazen Shihab None; Sergio Li Calzi None; Yvonne Adu-Agyeiwaah None; Cristiano Vieira None; Michael Boulton None; Carolina Rovarotto None; Matt George None; Dave Mann None; Mervin Yoder None; Maria Grant None
  • Footnotes
    Support  2 R01 EY012601-17
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1307. doi:
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      Yazen Shihab, Sergio Li Calzi, Yvonne Adu-Agyeiwaah, Cristiano Vieira, Michael E. Boulton, Carolina Francelin Rovarotto, Matt George, Dave Mann, Mervin C. Yoder, Maria B Grant; Human iPSC derived CD34+ cells and endothelial colony-forming cells (ECFCs) correct diabetic retinopathy (DR) in a model of type 2 diabetes. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1307.

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

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Abstract

Purpose : Vascular repair is supported by CD34+ hematopoietic cells and ECFCs. CD34+ cells migrate to areas of vascular injury and provide paracrine support, while the vascular wall harbors ECFCs that proliferate to replace injured endothelium. Both reparative populations are markedly diminished and dysfunctional in diabetic individuals that have vascular complications; thus, a need to replace these cells exists. In this study, we generated human induced pluripotent stem cells (hiPSCs)-derived CD34+ cells and hiPSC-derived ECFCs and evaluated their in vivo efficacy alone and in combination in a type 2 mouse (db/db mice) model of DR.

Methods : CD34+ cells and ECFCs were generated from human iPSCs (hiPSCs) following previously published protocols. hiPSC-CD34+ cells (104) and hiPSC-ECFCs (105) alone and in combination were injected into the vitreous of immunosuppressed db/db mice with 6 months of diabetes. Intravitreal saline injection served as control. One month after administering cells, mice underwent ERG and OCT analysis. Stem cell homing to the vasculature was evaluated by immunohistochemistry (IHC) using antibodies against human nuclear antigen to label cells and collagen IV to identify the vasculature.

Results : IHC showed that hiPSC-CD34+cells migrated to the retinal vessels and established a perivascular location. In contrast, hiPSC-ECFCs incorporated directly into retinal vessels. Mice injected with both cell types showed the expected distribution of each population. At one month post hiPSC-CD34+cell injection, an improvement was observed in the scotopic a- wave (56.3%, p<0.005) and b-wave (80.63%, p<0.001) but with ECFCs only the scotopic b-wave (88.69%, p<0.001) was improved compared to saline injected diabetic mice; however, unexpectedly the combination showed no improvement. OCT showed that administration of CD34+ cells alone significantly increased retinal thickness by 2.76% compared to saline injected db/db mice (p<0.047) while the combination of cells had a much greater increase in thickness by 10.41% (p<0.0001).

Conclusions : Our studies support the therapeutic potential of hiPSC-CD34+ cells and hiPSC-ECFCs to independently and collectively improve key aspects of retinal structure and function and represents a new therapeutic strategy for preventing/reversing aspects of DR.

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

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