Potential role of intravitreal human placental stem cell implants in inhibiting progression of diabetic retinopathy in type 2 diabetes: neuroprotective growth factors in the vitreous

Scalinci, Sergio Zaccaria; Scorolli, L.; Corradetti, Giulia; Domanico, Daniela; Meduri, Alessandro; Bifani, Mario; Siravo, D

doi:10.2147/opth.s21161

Cited by 29 publications

(23 citation statements)

References 20 publications

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“…[ 66 ] Although DR is one of the most important visually debilitating diseases, only one ongoing clinical trial is targeting DR. [ 67 ] This may be due to the low number of experimental studies conducted in this specific area. Though several studies have pointed to various beneficial effects of stem cells in DR, [ 17 , 52 , 68 – 70 ] the present study demonstrates a detailed ERG analysis, specifically an improvement in OP waves.…”

Section: Discussionmentioning

confidence: 53%

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Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats

et al. 2016

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Diabetic retinopathy is the most common cause of legal blindness in developed countries at middle age adults. In this study diabetes was induced by streptozotocin (STZ) in male Wistar albino rats. After 3 months of diabetes, rights eye were injected intravitreally with green fluorescein protein (GFP) labelled bone marrow derived stem cells (BMSC) and left eyes with balanced salt solution (Sham). Animals were grouped as Baseline (n = 51), Diabetic (n = 45), Diabetic+BMSC (n = 45 eyes), Diabetic+Sham (n = 45 eyes), Healthy+BMSC (n = 6 eyes), Healthy+Sham (n = 6 eyes). Immunohistology analysis showed an increased retinal gliosis in the Diabetic group, compared to Baseline group, which was assessed with GFAP and vimentin expression. In the immunofluorescence analysis BMSC were observed to integrate mostly into the inner retina and expressing GFP. Diabetic group had prominently lower oscillatory potential wave amplitudes than the Baseline group. Three weeks after intravitreal injection Diabetic+BMSC group had significantly better amplitudes than the Diabetic+Sham group. Taken together intravitreal BMSC were thought to improve visual function.

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Section: Discussionmentioning

confidence: 53%

“…[ 50 , 51 ] It has also been demonstrated that BMSC can increase the retinal and intravitreal concentrations of neuroprotective growth factors. [ 52 ]…”

Section: Discussionmentioning

confidence: 99%

Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats

et al. 2016

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“…In this animal model, the intravitreal administration of MSCs provides trophic support to the damaged tissue, and increased RGC survival [ 21 ]. Additionally, Yu et al reported that intravitreal MSC transplantation was neuroprotective after episcleral vein ligature, which can cause moderate ocular hypertension and RGC loss [ 54 ], and the same neuroprotective factors were also elevated in the vitreous cavity after the intravitreal administration of human placental stem cells in an animal model of DR [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the retina of diabetic mice

et al. 2016

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BackgroundDiabetic retinopathy is a common complication of diabetes and the leading cause of irreversible vision loss in the Western world. The reduction in color/contrast sensitivity due to the loss of neural cells in the ganglion cell layer of the retina is an early event in the onset of diabetic retinopathy. Multipotent mesenchymal stromal cells (MSCs) are an attractive tool for the treatment of neurodegenerative diseases, since they could differentiate into neuronal cells, produce high levels of neurotrophic factors and reduce oxidative stress. Our aim was to determine whether the intravitreal administration of adipose-derived MSCs was able to prevent the loss of retinal ganglion cells in diabetic mice.MethodsDiabetes was induced in C57BL6 mice by the administration of streptozotocin. When retinal pro-damage mechanisms were present, animals received a single intravitreal dose of 2 × 105 adipose-derived MSCs or the vehicle. Four and 12 weeks later we evaluated: (a) retinal ganglion cell number (immunofluorescence); (b) neurotrophic factor levels (real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA)); (c) retinal apoptotic rate (TUNEL); (d) retinal levels of reactive oxygen species and oxidative damage (ELISA); (e) electrical response of the retina (electroretinography); (f) pro-angiogenic and anti-angiogenic factor levels (RT-qPCR and ELISA); and (g) retinal blood vessels (angiography). Furthermore, 1, 4, 8 and 12 weeks post-MSC administration, the presence of donor cells in the retina and their differentiation into neural and perivascular-like cells were assessed (immunofluorescence and flow cytometry).ResultsMSC administration completely prevented retinal ganglion cell loss. Donor cells remained in the vitreous cavity and did not differentiate into neural or perivascular-like cells. Nevertheless, they increased the intraocular levels of several potent neurotrophic factors (nerve growth factor, basic fibroblast growth factor and glial cell line-derived neurotrophic factor) and reduced the oxidative damage in the retina. Additionally, MSC administration has a neutral effect on the electrical response of the retina and did not result in a pathological neovascularization.ConclusionsIntravitreal administration of adipose-derived MSCs triggers an effective cytoprotective microenvironment in the retina of diabetic mice. Thus, MSCs represent an interesting tool in order to prevent diabetic retinopathy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0299-y) contains supplementary material, which is available to authorized users.

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“…A single intravitreal injection of placental-derived MSCs into diabetic rats has also resulted in a significant decrease in retinal cell apoptosis, such effect being related to increased intravitreal concentration of several neuroprotective growth factors [103].…”

Section: Msc-related Therapy For Diabetic Retinopathymentioning

confidence: 99%

Mesenchymal Stem Cell Therapy in Type 1 Diabetes Mellitus and Its Main Complications: From Experimental Findings to Clinical Practice

Ezquer

Arango-Rodríguez²,

Giraud-Billoud³

et al. 2014

J Stem Cell Res Ther

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Potential role of intravitreal human placental stem cell implants in inhibiting progression of diabetic retinopathy in type 2 diabetes: neuroprotective growth factors in the vitreous

Cited by 29 publications

References 20 publications

Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats

Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats

Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the retina of diabetic mice

Mesenchymal Stem Cell Therapy in Type 1 Diabetes Mellitus and Its Main Complications: From Experimental Findings to Clinical Practice

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