April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Adipose-derived stem cell conditioned media protects against diabetic retinal vasculopathy in vivo
Author Affiliations & Notes
  • Molly Rose Kelly-Goss
    Biomedical Engineering, University of Virginia, Charlottesville, VA
    Ophthalmology, University of Virginia, Charlottesville, VA
  • Thomas Allan Mendel
    Ophthalmology, University of Virginia, Charlottesville, VA
    Pathology, University of Virginia, Charlottesville, VA
  • Alexander M Guendel
    Ophthalmology, University of Virginia, Charlottesville, VA
  • Howard Clifton Ray
    Biomedical Engineering, University of Virginia, Charlottesville, VA
  • Shayn Peirce
    Biomedical Engineering, University of Virginia, Charlottesville, VA
  • Paul Andrew Yates
    Ophthalmology, University of Virginia, Charlottesville, VA
  • Footnotes
    Commercial Relationships Molly Kelly-Goss, None; Thomas Mendel, None; Alexander Guendel, None; Howard Ray, None; Shayn Peirce, None; Paul Yates, Genentech/Roche (C), Owner RetiVue LLC (I), RetoVue LLC (E), U.S. Provisional Patent Application Serial No. 61/684,375 (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4904. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Molly Rose Kelly-Goss, Thomas Allan Mendel, Alexander M Guendel, Howard Clifton Ray, Shayn Peirce, Paul Andrew Yates; Adipose-derived stem cell conditioned media protects against diabetic retinal vasculopathy in vivo. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4904.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: The purpose of this work is to determine if intravitreally injected cell conditioned media (CCM) from adipose-derived stem cells (ASCs) can protect against vascular dysfunction secondary to diabetic retinopathy (DR). Previous work has demonstrated that ASCs injected intravitreally can differentiate into functional pericytes and exert a vascular protective effect, even without ASC integration into the network. The objective of this study was to isolate the contribution of a paracrine effect of ASCs in an in vivo model of retinal vasculopathy through injection of CCM.

Methods: The stromal vascular fraction was collected from mouse gonadal adipose tissue, and ASCs were isolated through serial passage. Cells were passaged to P4 and the media was conditioned for 24 hours. CCM was concentrated to obtain soluble growth factor levels comparable to ASC populations injected in prior studies. Injections were performed once a week for four weeks in five-week-old Akimba mice to determine the impact of CCM on vascular retention in a model of DR onset. One week after the last injection, retinal wholemounts were harvested and prepared, and vascular networks were stained with lectin for analysis in ImageJ.

Results: When injected intravitreally, CCM from healthy ASCs protect early diabetic retinal capillaries. CCM enhanced vascular stability as compared to PBS control injections. Retinal networks exhibited a reduction in capillary network dropout in the CCM injected eye. While avascular area only decreased slightly in the control injection (98.6% vs. 92.5%), vascular length density was significantly decreased. No untoward effects were noted on the neural retina or lens as a result of injection of CCM as compared to PBS control.

Conclusions: Our data suggests ASC-derived pericytes have a paracrine effect that promotes stabilization in the diabetic retinal microvasculature. When CCM was injected intravitreally, vascular protective effects were similar to those previously observed in cell-injected studies from the same cell populations. As the vascular progenitors in adipose tissue are being evaluated for regenerative DR therapy, a CCM therapy could allow for lower-risk intravitreal injections than with potentially immunogenic ASCs. This also opens the door to future studies comparing the quality of CCM from both diabetic and healthy adipose to determine if non-autologous approaches have therapeutic potential.

Keywords: 499 diabetic retinopathy • 721 stem cells • 561 injection  
×
×

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.

×