Improvement of Corneal Nerve Regeneration in Diabetic Rats UsingWharton's Jelly-Derived Mesenchymal Stem Cells and theirConditioned Medium

Document Type : Original Article

Authors
Pitra Ariesta Shinta Dewi 1
Ratna Sitompul 2 , 3 , 4
Jeanne Adiwinata Pawitan 5 , 3 , 4
Aroem Naroeni 6 , 7
Radiana Dewayani Antarianto 7
1 Doctoral Programme Biomedical Sciences, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
2 Department of Histology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
3 Stem Cell Medical Technology Integrated Service Unit, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
4 Stem Cell and Tissue Engineering (SCTE) Research Center, Indonesia Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
5 Department of Histology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
6 Stem Cell Medical Technology Integrated Service Unit, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
7 Virology and Cancer Pathobiology Research Center, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
10.22088/IJMCM.BUMS.11.3.180
Abstract
To investigate the efficacy of Wharton's jelly mesenchymal stem cells (WJSCs) and their
conditioned medium (CM) for corneal nerve regeneration in rats with diabetic keratopathy.
Streptozotocin (STZ)-induced male diabetic (DM) rats (250–300 g) were divided into four groups
(n=7/group): Control, DM, DM with WJSCs (DM+WJ), and DM with CM treatment (DM+CM).
DM+WJ and DM+CM group received WJSCs or CM, respectively, topically with eye drops.
Corneal sensibility, corneal epithelial layer integrity, histology, expression of GAP-43 and TUBB3
on mRNA level and their immunohistochemical expression were examined after two weeks of
treatment. There were changes in corneal sensibility and corneal integrity between normal control
and diabetic groups with/without WJSC or CM injection. Total central corneal thickness was
significantly higher in DM+CM (249.81 ± 43.85 μm) than in control (174.72 ± 44.12 μm, P=0.004)
and DM groups (190.15 ± 9.63 μm, P=0.03). GAP-43 mRNA expression levels of DM+WJ and
DM+CM groups were higher compared with DM and control groups. TUBB3 mRNA level was
increased after CM (P=0.047), but not after WJSCs treatment (P=1.00). GAP-43 and TUBB3
immunohistochemical expression of nerve fibers along the epithelial layer significantly increased
in DM+WJ and DM+CM compared with DM group. Our findings showed that WJSCs and their
CM improved corneal nerve regeneration in rats with diabetic keratopathy.
Keywords
stem cells
Wharton's jelly
conditioned medium
diabetic rats
GAP-43
TUBB3