Limits...
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 SZ, Scorolli L, Corradetti G, Domanico D, Vingolo EM, Meduri A, Bifani M, Siravo D - Clin Ophthalmol (2011)

Bottom Line: Intravitreal injection of human mesenchymal stem cells has been shown to be effective in slowing the progression of diabetic retinopathy in an animal model of chemically induced diabetes mellitus.Twenty-two Lewis rats were treated with an intravitreal human mesenchymal stem cell microinjection.Increased intravitreal and retinal concentrations of neuroprotective growth factors in rats confirm the neuroprotective activity of human mesenchymal stem cells in diabetic retinopathy.

View Article: PubMed Central - PubMed

Affiliation: Glaucoma and Low Vision Study Center, Department of General Surgery and Organ Transplants, University of Bologna, Bologna. sergio.unibo@unibo.it

ABSTRACT

Background: Intravitreal injection of human mesenchymal stem cells has been shown to be effective in slowing the progression of diabetic retinopathy in an animal model of chemically induced diabetes mellitus. We studied changes in growth factor levels released from human mesenchymal stem cells in the vitreous cavity as well as changes in growth factor levels in host retinal neurons following intravitreal injection.

Methods: Twenty-two Lewis rats were treated with an intravitreal human mesenchymal stem cell microinjection. Determination of neurotrophic factors released by human mesenchymal stem cells in the vitreous was carried out using real-time polymerase chain reaction.

Results: Detectable levels of neurotrophic factors were identified postoperatively in the vitreous of all rats.

Conclusion: Increased intravitreal and retinal concentrations of neuroprotective growth factors in rats confirm the neuroprotective activity of human mesenchymal stem cells in diabetic retinopathy.

No MeSH data available.


Related in: MedlinePlus

Vitreous concentration of neuroprotective growth factor in Group A (treated) and in Group B (controls). Brain-derived neurotrophic factor, ciliary-derived neurotrophic factor, basic fibroblast growth factor, glial-derived neurotrophic factor, and nerve growth factor are significant neuroprotective growth factors tested in the vitreous in both Group A and Group B. They were significantly higher (P < 0.05) in rats affected by diabetic retinopathy treated by human stem cell transplant compared with Group B controls.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3104799&req=5

f2-opth-5-691: Vitreous concentration of neuroprotective growth factor in Group A (treated) and in Group B (controls). Brain-derived neurotrophic factor, ciliary-derived neurotrophic factor, basic fibroblast growth factor, glial-derived neurotrophic factor, and nerve growth factor are significant neuroprotective growth factors tested in the vitreous in both Group A and Group B. They were significantly higher (P < 0.05) in rats affected by diabetic retinopathy treated by human stem cell transplant compared with Group B controls.

Mentions: Fluorangiography examination showed that rats receiving the intravitreal human placental stem cell transplant had a marked improvement in the evolution of diabetic retinopathy. Group A showed markedly decreased areas of hypofluorescence and hypoperfusion, due to the ischemia leading to evolution of diabetic retinopathy and absence of leakage phenomena, which indicates slowing and/or stabilization of diabetic retinopathy. On fluorangiographic examination, Group B rats demonstrated retinal hyperfluorescence (leakage) associated with significant areas of hypofluorescence, and microaneurysms, neovascularization, and ischemic areas, both preoperatively and postoperatively. The fluorangiographic examination was strictly qualitative, so was performed by the same operator to reduce the chances of observational errors. Moreover, determination of neurotrophic and growth factors having an anti-apoptotic, antineoangiogenic, and neuroprotective role and released by the transplanted human placental stem cells in Group A were evaluated using vitreous real-time polymerase chain reaction. The growth factors released were ligands of two large families of receptors, ie, the family of transmembrane receptors with tyrosine kinase activity and the family of neurotrophic receptors. The growth factors we evaluated were basic fibroblastic growth factor, nerve growth factor, brain-derived neurotrophic factor, ciliary-derived neurotrophic factor, and glial-derived neurotrophic factor. All these growth factors were detected in all vitreous samples tested. Real-time polymerase chain reaction showed notable levels of vitreous expression of neurotrophic factors. Qualitative and quantitative analysis of these factors showed that the greatest peaks of concentration at the endovitreal level were reached by brain-derived neurotrophic factor and ciliary-derived neurotrophic factor in rats with transplanted human stem cells. Significantly higher levels of basic fibroblast growth factor, nerve growth factor, brain-derived neurotrophic factor, ciliary-derived neurotrophic factor, and glial-derived neurotrophic factor were observed in the vitreous samples of rats in group A compared with Group B controls. All neuroprotective growth factor levels were significantly higher (P < 0.05) in rats affected by diabetic retinopathy and with transplanted human stem cells than in Group B controls. Both brain-derived neurotrophic factor and ciliary-derived neurotrophic factor reached levels of 107.99 pg/mL ± 0.002 (P < 0.05) in Group A rats, while the median level of brain-derived neurotrophic factor and ciliary-derived neurotrophic factor in Group B controls was 38.7 pg/mL ± 0.023. This difference was statistically significant (P < 0.05). Furthermore, a significant negative association was observed between vascular endothelial growth factor and proinflammatory cytokine levels and the progression of the diabetic retinopathy after transplantation in Group A rats (Figure 2).


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 SZ, Scorolli L, Corradetti G, Domanico D, Vingolo EM, Meduri A, Bifani M, Siravo D - Clin Ophthalmol (2011)

Vitreous concentration of neuroprotective growth factor in Group A (treated) and in Group B (controls). Brain-derived neurotrophic factor, ciliary-derived neurotrophic factor, basic fibroblast growth factor, glial-derived neurotrophic factor, and nerve growth factor are significant neuroprotective growth factors tested in the vitreous in both Group A and Group B. They were significantly higher (P < 0.05) in rats affected by diabetic retinopathy treated by human stem cell transplant compared with Group B controls.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104799&req=5

f2-opth-5-691: Vitreous concentration of neuroprotective growth factor in Group A (treated) and in Group B (controls). Brain-derived neurotrophic factor, ciliary-derived neurotrophic factor, basic fibroblast growth factor, glial-derived neurotrophic factor, and nerve growth factor are significant neuroprotective growth factors tested in the vitreous in both Group A and Group B. They were significantly higher (P < 0.05) in rats affected by diabetic retinopathy treated by human stem cell transplant compared with Group B controls.
Mentions: Fluorangiography examination showed that rats receiving the intravitreal human placental stem cell transplant had a marked improvement in the evolution of diabetic retinopathy. Group A showed markedly decreased areas of hypofluorescence and hypoperfusion, due to the ischemia leading to evolution of diabetic retinopathy and absence of leakage phenomena, which indicates slowing and/or stabilization of diabetic retinopathy. On fluorangiographic examination, Group B rats demonstrated retinal hyperfluorescence (leakage) associated with significant areas of hypofluorescence, and microaneurysms, neovascularization, and ischemic areas, both preoperatively and postoperatively. The fluorangiographic examination was strictly qualitative, so was performed by the same operator to reduce the chances of observational errors. Moreover, determination of neurotrophic and growth factors having an anti-apoptotic, antineoangiogenic, and neuroprotective role and released by the transplanted human placental stem cells in Group A were evaluated using vitreous real-time polymerase chain reaction. The growth factors released were ligands of two large families of receptors, ie, the family of transmembrane receptors with tyrosine kinase activity and the family of neurotrophic receptors. The growth factors we evaluated were basic fibroblastic growth factor, nerve growth factor, brain-derived neurotrophic factor, ciliary-derived neurotrophic factor, and glial-derived neurotrophic factor. All these growth factors were detected in all vitreous samples tested. Real-time polymerase chain reaction showed notable levels of vitreous expression of neurotrophic factors. Qualitative and quantitative analysis of these factors showed that the greatest peaks of concentration at the endovitreal level were reached by brain-derived neurotrophic factor and ciliary-derived neurotrophic factor in rats with transplanted human stem cells. Significantly higher levels of basic fibroblast growth factor, nerve growth factor, brain-derived neurotrophic factor, ciliary-derived neurotrophic factor, and glial-derived neurotrophic factor were observed in the vitreous samples of rats in group A compared with Group B controls. All neuroprotective growth factor levels were significantly higher (P < 0.05) in rats affected by diabetic retinopathy and with transplanted human stem cells than in Group B controls. Both brain-derived neurotrophic factor and ciliary-derived neurotrophic factor reached levels of 107.99 pg/mL ± 0.002 (P < 0.05) in Group A rats, while the median level of brain-derived neurotrophic factor and ciliary-derived neurotrophic factor in Group B controls was 38.7 pg/mL ± 0.023. This difference was statistically significant (P < 0.05). Furthermore, a significant negative association was observed between vascular endothelial growth factor and proinflammatory cytokine levels and the progression of the diabetic retinopathy after transplantation in Group A rats (Figure 2).

Bottom Line: Intravitreal injection of human mesenchymal stem cells has been shown to be effective in slowing the progression of diabetic retinopathy in an animal model of chemically induced diabetes mellitus.Twenty-two Lewis rats were treated with an intravitreal human mesenchymal stem cell microinjection.Increased intravitreal and retinal concentrations of neuroprotective growth factors in rats confirm the neuroprotective activity of human mesenchymal stem cells in diabetic retinopathy.

View Article: PubMed Central - PubMed

Affiliation: Glaucoma and Low Vision Study Center, Department of General Surgery and Organ Transplants, University of Bologna, Bologna. sergio.unibo@unibo.it

ABSTRACT

Background: Intravitreal injection of human mesenchymal stem cells has been shown to be effective in slowing the progression of diabetic retinopathy in an animal model of chemically induced diabetes mellitus. We studied changes in growth factor levels released from human mesenchymal stem cells in the vitreous cavity as well as changes in growth factor levels in host retinal neurons following intravitreal injection.

Methods: Twenty-two Lewis rats were treated with an intravitreal human mesenchymal stem cell microinjection. Determination of neurotrophic factors released by human mesenchymal stem cells in the vitreous was carried out using real-time polymerase chain reaction.

Results: Detectable levels of neurotrophic factors were identified postoperatively in the vitreous of all rats.

Conclusion: Increased intravitreal and retinal concentrations of neuroprotective growth factors in rats confirm the neuroprotective activity of human mesenchymal stem cells in diabetic retinopathy.

No MeSH data available.


Related in: MedlinePlus