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Endothelial progenitor dysfunction in the pathogenesis of diabetic retinopathy: treatment concept to correct diabetes-associated deficits.

Li Calzi S, Neu MB, Shaw LC, Grant MB - EPMA J (2010)

Bottom Line: EPCs can be isolated using cell sorting by surface phenotype selection or in vitro cell culture.For freshly isolated cells, EPC cell sorting is heavily dependent on the surface markers used; EPCs can also be isolated by in vitro propagation of heterogeneous mixtures of cells in culture using adhesion to specific substrates and cell growth characteristics. in vitro isolation enables consistent reproducibility and using this approach at least two distinct types of EPCs with different angiogenic properties have been identified from adult peripheral and umbilical cord blood; early EPCs (eEPCs) and late outgrowth endothelial progenitor cells (OECs).Since ischemic retinopathies are leading causes of blindness, they are a potential disease target for EPC-based therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.

ABSTRACT
Progressive obliteration of the retinal microvessels is a characteristic of diabetic retinopathy and the resultant retinal ischemia can lead to sight-threatening macular edema, macular ischemia and ultimately preretinal neovascularization. Bone marrow derived endothelial progenitor cells (EPCs) play a critical role in vascular maintenance and repair. There is still great debate about the most appropriate markers that define an EPC. EPCs can be isolated using cell sorting by surface phenotype selection or in vitro cell culture. For freshly isolated cells, EPC cell sorting is heavily dependent on the surface markers used; EPCs can also be isolated by in vitro propagation of heterogeneous mixtures of cells in culture using adhesion to specific substrates and cell growth characteristics. in vitro isolation enables consistent reproducibility and using this approach at least two distinct types of EPCs with different angiogenic properties have been identified from adult peripheral and umbilical cord blood; early EPCs (eEPCs) and late outgrowth endothelial progenitor cells (OECs). Emerging studies demonstrate the potential of these cells in revascularization of ischemic/injured retina in animal models of retinal disease. Since ischemic retinopathies are leading causes of blindness, they are a potential disease target for EPC-based therapy. In this chapter, we summarize the current knowledge about EPCs and discuss the possibility of cellular therapy for treatment of diabetic macular ischemia and the vasodegenerative phase of diabetic retinopathy. We also report current pharmacological options that can be utilized to correct diabetes associated defects in EPCs so as to enhance the therapeutic utility of these cells.

No MeSH data available.


Related in: MedlinePlus

Schematic of the hypothetic diabetic retinopathy progress. In physiological conditions, CD34+ EPCs contribute to routine blood vessel maintenance through eNOS activation and NO-mediated stimulation of CD14+ EPCs. In diabetes, initially, cytokines like stem cell factor (SCF), monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) released by dysfunctional CD34+ EPCs initiate CD14+ EPC-mediated aberrant vascular repair resulting in retinal ischemia. This phase is referred to as non proliferative diabetic retinopathy (NPDR). The vasodegenerative phase of diabetic retinopathy associated with reduced reparative function of EPCs evolves in the proliferative diabetic retinopathy (PDR). This phase is characterized by pathological neovascularization seen in the diabetic retina
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Fig5: Schematic of the hypothetic diabetic retinopathy progress. In physiological conditions, CD34+ EPCs contribute to routine blood vessel maintenance through eNOS activation and NO-mediated stimulation of CD14+ EPCs. In diabetes, initially, cytokines like stem cell factor (SCF), monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) released by dysfunctional CD34+ EPCs initiate CD14+ EPC-mediated aberrant vascular repair resulting in retinal ischemia. This phase is referred to as non proliferative diabetic retinopathy (NPDR). The vasodegenerative phase of diabetic retinopathy associated with reduced reparative function of EPCs evolves in the proliferative diabetic retinopathy (PDR). This phase is characterized by pathological neovascularization seen in the diabetic retina

Mentions: Our group and others have evidence that the development of acellular capillaries may be due to failed attempts at repair of injured capillaries and persistence of ischemia. For the last 10 years, our group has focused on understanding the basic mechanism responsible for the diabetes-associated defect in EPC function. Correcting this defect may allow the use of a diabetic patient’s own EPCs for repair of their injured retinal and systemic vasculature. Specifically in the retina, correction of this dysfunction could treat early and intermediate stages of vasodegeneration to enhance vessel repair, reverse ischemia, and prevent progression to the late stages of DR (Fig. 5). However before EPCs can be used therapeutically in DR to reendothelialize acellular capillaries and eliminate retinal ischemia, several key questions must be answered. What triggers this phenotypic change in diabetic cells taking them from reparative to deleterious? What is the best reparative BMDC population? Are some subpopulations more resistant to the injurious effects of diabetes? Should the BM be a target for DR therapy?Fig. 5


Endothelial progenitor dysfunction in the pathogenesis of diabetic retinopathy: treatment concept to correct diabetes-associated deficits.

Li Calzi S, Neu MB, Shaw LC, Grant MB - EPMA J (2010)

Schematic of the hypothetic diabetic retinopathy progress. In physiological conditions, CD34+ EPCs contribute to routine blood vessel maintenance through eNOS activation and NO-mediated stimulation of CD14+ EPCs. In diabetes, initially, cytokines like stem cell factor (SCF), monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) released by dysfunctional CD34+ EPCs initiate CD14+ EPC-mediated aberrant vascular repair resulting in retinal ischemia. This phase is referred to as non proliferative diabetic retinopathy (NPDR). The vasodegenerative phase of diabetic retinopathy associated with reduced reparative function of EPCs evolves in the proliferative diabetic retinopathy (PDR). This phase is characterized by pathological neovascularization seen in the diabetic retina
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3008583&req=5

Fig5: Schematic of the hypothetic diabetic retinopathy progress. In physiological conditions, CD34+ EPCs contribute to routine blood vessel maintenance through eNOS activation and NO-mediated stimulation of CD14+ EPCs. In diabetes, initially, cytokines like stem cell factor (SCF), monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) released by dysfunctional CD34+ EPCs initiate CD14+ EPC-mediated aberrant vascular repair resulting in retinal ischemia. This phase is referred to as non proliferative diabetic retinopathy (NPDR). The vasodegenerative phase of diabetic retinopathy associated with reduced reparative function of EPCs evolves in the proliferative diabetic retinopathy (PDR). This phase is characterized by pathological neovascularization seen in the diabetic retina
Mentions: Our group and others have evidence that the development of acellular capillaries may be due to failed attempts at repair of injured capillaries and persistence of ischemia. For the last 10 years, our group has focused on understanding the basic mechanism responsible for the diabetes-associated defect in EPC function. Correcting this defect may allow the use of a diabetic patient’s own EPCs for repair of their injured retinal and systemic vasculature. Specifically in the retina, correction of this dysfunction could treat early and intermediate stages of vasodegeneration to enhance vessel repair, reverse ischemia, and prevent progression to the late stages of DR (Fig. 5). However before EPCs can be used therapeutically in DR to reendothelialize acellular capillaries and eliminate retinal ischemia, several key questions must be answered. What triggers this phenotypic change in diabetic cells taking them from reparative to deleterious? What is the best reparative BMDC population? Are some subpopulations more resistant to the injurious effects of diabetes? Should the BM be a target for DR therapy?Fig. 5

Bottom Line: EPCs can be isolated using cell sorting by surface phenotype selection or in vitro cell culture.For freshly isolated cells, EPC cell sorting is heavily dependent on the surface markers used; EPCs can also be isolated by in vitro propagation of heterogeneous mixtures of cells in culture using adhesion to specific substrates and cell growth characteristics. in vitro isolation enables consistent reproducibility and using this approach at least two distinct types of EPCs with different angiogenic properties have been identified from adult peripheral and umbilical cord blood; early EPCs (eEPCs) and late outgrowth endothelial progenitor cells (OECs).Since ischemic retinopathies are leading causes of blindness, they are a potential disease target for EPC-based therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.

ABSTRACT
Progressive obliteration of the retinal microvessels is a characteristic of diabetic retinopathy and the resultant retinal ischemia can lead to sight-threatening macular edema, macular ischemia and ultimately preretinal neovascularization. Bone marrow derived endothelial progenitor cells (EPCs) play a critical role in vascular maintenance and repair. There is still great debate about the most appropriate markers that define an EPC. EPCs can be isolated using cell sorting by surface phenotype selection or in vitro cell culture. For freshly isolated cells, EPC cell sorting is heavily dependent on the surface markers used; EPCs can also be isolated by in vitro propagation of heterogeneous mixtures of cells in culture using adhesion to specific substrates and cell growth characteristics. in vitro isolation enables consistent reproducibility and using this approach at least two distinct types of EPCs with different angiogenic properties have been identified from adult peripheral and umbilical cord blood; early EPCs (eEPCs) and late outgrowth endothelial progenitor cells (OECs). Emerging studies demonstrate the potential of these cells in revascularization of ischemic/injured retina in animal models of retinal disease. Since ischemic retinopathies are leading causes of blindness, they are a potential disease target for EPC-based therapy. In this chapter, we summarize the current knowledge about EPCs and discuss the possibility of cellular therapy for treatment of diabetic macular ischemia and the vasodegenerative phase of diabetic retinopathy. We also report current pharmacological options that can be utilized to correct diabetes associated defects in EPCs so as to enhance the therapeutic utility of these cells.

No MeSH data available.


Related in: MedlinePlus