Abstract
Objectives: Transplantation of stem cells is one of the
approaches to treat retinal diseases. Our objective was
to determine whether adipose-derived stem cell
transplant can survive and migrate in the injured
retina using a sodium iodate model for the pigmented
retinal epithelium injury.
Materials and Methods: The adipose-derived stem cells
were isolated from male albino Sprague-Dawley rats
and labeled with DiI so as to track the transplants in
the subretinal space. Retinal pigmented epithelium
damage was induced by retro-orbital sinus sodium
iodate injection (40 mg/kg) into albino Sprague-
Dawley rats. Four weeks after transplantation, the
eyeballs were fixed in 4% paraformaldehyde and cut
with cryostat. The eyeballs were serially sectioned
along the vertical meridian. Cryosections were from
the full length of the retina and passing through the
optic nerve head. The survival and migration of
transplanted cells were assessed.
Results: Sodium iodate selectively destroyed the
retinal pigmented epithelium layer. The transplanted
cells incorporated into the retinal pigmented
epithelium layer, perhaps differentiating into a retinal
pigmented epithelium phenotype. The transplanted
cells were located in the subretinal space; after 4
weeks, some were observed in the retinal pigmented
epithelium layer.
Conclusions: We found that adipose-derived stem cells
survived for 4 weeks after transplantation and
migrated into the retinal pigmented epithelium layer.
Key words: Cytotherapy, Eye disorders, Retinal disease,
Retinal pigmented epithelium layer
Introduction
Retinal pigment epithelium (RPE) dysfunction has
been linked to many devastating eye disorders,
including age-related macular degeneration and
hereditary disorders such as Stargardt disease and
retinitis pigmentosa.
1
The integrity of the RPE is
essential for retinal function and visual health. The
RPE consists of a monolayer of cuboidal cells that
separates the photoreceptors and the choroid,
forming the blood-retina barrier via tight junctions. It
serves an integral function in the visual cycle by
phagocytosis of the rod and the cone outer segments
following shedding into the subretinal space and the
production of paracrine factors for the retina. The
RPE is also responsible for movement of ions and
water so as to maintain a proper state of dehydration
for visual clarity, and its pigmentation absorbs stray
light that would otherwise degrade the visual
image.
2,3
Pigmentation of the RPE layer is due to the
presence of melanosomes, which are organelles
containing the light-absorbing pigment melanin. The
retinal pigment cells are considered to be postmitotic
cells at normal conditions.
4
They can regenerate and
proliferate in an injured retina.
5
In addition, a low
dose of sodium iodate could induce a regenerative
mechanism
6
; however, failure of regeneration has
been reported with high doses, which could be due
to either the retinal stem cells
7
or the marginal RPE
cells.
8
Therefore, a high-dose model can be useful in
evaluating replacement cell therapy for restoring lost
cells. However, the success of stem cell therapy is
highly dependent on the ability of donor cells to
survive, migrate, differentiate, and integrate into the
desired location.
On the other hand, mesenchymal stem cells,
multipotent cells, are a potential autologous source
Copyright © Başkent University 2017
Printed in Turkey. All Rights Reserved.
Survival and Migration of Adipose-Derived Stem Cells
Transplanted in the Injured Retina
Hamid Aboutaleb Kadkhodaeian,
1
Taki Tiraihi,
1
Hamid Ahmadieh,
2
Hossein Ziaei Ardakani,
2
Narsis Daftarian,
2
Taher Taheri
3
From the
1
Department of Anatomical Sciences, School of Medical Sciences, Tarbiat Modares
University, Tehran, Iran; and
2
Department of Ophthalmology, Labbafinejad Medical Center,
Tehran, Iran; and the
3
Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran,
Iran
Acknowledgements: The project was funded by Shefa Neuroscience Research Center at Khatam
Al-Anbia Hospital, Tehran, Iran. The authors have no conflicts of interest to declare. We are
grateful for the support of the Faculty of Medical Sciences, Tarbiat Modares University, Tehran,
Iran. We also express our deep gratitude for Mrs. H. H. AliAkbar for editing the manuscript.
Corresponding author: Taki Tiraihi, Department of Anatomical Sciences, School of Medical
Sciences, Tarbiat Modares University, PO Box 14155-4838, Tehran, Iran
Phone: +98 21 88011001 E-mail: takialtr@modares.ac.ir, ttiraihi@gmail.com
Experimental and Clinical Transplantation (2017)
ArtIcle
DOI: 10.6002/ect.2016.0235