Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells

Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells Sergio Caballero 1 , Nilanjana Sengupta 1 , Aqeela Afzal 1 , Kyung-Hee Chang 1 , Sergio Li Calzi 1 , Dennis L. Guberski 2 , Timothy S. Kern 3 and Maria B. Grant 1 1 Program in Stem Cell Biology, Depar...

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Vydané v:Diabetes (New York, N.Y.) Ročník 56; číslo 4; s. 960 - 967
Hlavní autori: Caballero, Sergio, Sengupta, Nilanjana, Afzal, Aqeela, Chang, Kyung-Hee, Li Calzi, Sergio, Guberski, Dennis L., Kern, Timothy S., Grant, Maria B.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Alexandria, VA American Diabetes Association 01.04.2007
Predmet:
Acute Disease
Analysis
Animals
Antigens, CD - blood
Antigens, CD34 - blood
Biological and medical sciences
Blood vessels
Cell Transplantation
Chronic Disease
Diabetes
Diabetes Mellitus, Experimental - therapy
Diabetes. Impaired glucose tolerance
Diabetic Angiopathies - therapy
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Endothelial growth factors
Endothelium, Vascular - transplantation
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Female
Genetic aspects
Humans
Ischemia
Ischemia - therapy
Laboratories
Localization
Male
Medical sciences
Mice
Mice, Inbred C57BL
Ostomy
Peripheral vascular diseases
Rats
Rats, Inbred Strains
Retinal Vessels - injuries
Vascular endothelial growth factor
Endocrinopathy
Endothelial cell
Ischemia
Diabetes mellitus
Precursor cell
Cardiovascular disease
Repair
ISSN:0012-1797, 1939-327X
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Abstract Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells Sergio Caballero 1 , Nilanjana Sengupta 1 , Aqeela Afzal 1 , Kyung-Hee Chang 1 , Sergio Li Calzi 1 , Dennis L. Guberski 2 , Timothy S. Kern 3 and Maria B. Grant 1 1 Program in Stem Cell Biology, Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 2 Biomedical Research Models, Worcester, Massachusetts 3 Department of Medicine, Case Western Reserve University, Cleveland, Ohio Address correspondence and reprint requests to Maria B. Grant, MD, Pharmacology and Therapeutics, University of Florida, P.O. Box 100267, Gainesville, FL 32610-0267. E-mail: grantma{at}pharmacology.ufl.edu Abstract Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded in diabetes. We previously demonstrated that EPCs isolated from diabetic patients have a profound inability to migrate in vitro. We asked whether EPCs from normal individuals are better able to repopulate degenerate (acellular) retinal capillaries in chronic (diabetes) and acute (ischemia/reperfusion [I/R] injury and neonatal oxygen-induced retinopathy [OIR]) animal models of ocular vascular damage. Streptozotocin-induced diabetic mice, spontaneously diabetic BBZDR/Wor rats, adult mice with I/R injury, or neonatal mice with OIR were injected within the vitreous or the systemic circulation with fluorescently labeled CD34 + cells from either diabetic patients or age- and sex-matched healthy control subjects. At specific times after administering the cells, the degree of vascular repair of the acellular capillaries was evaluated immunohistologically and quantitated. In all four models, healthy human (hu)CD34 + cells attached and assimilated into vasculature, whereas cells from diabetic donors uniformly were unable to integrate into damaged vasculature. These studies demonstrate that healthy huCD34 + cells can effectively repair injured retina and that there is defective repair of vasculature in patients with diabetes. Defective EPCs may be amenable to pharmacological manipulation and restoration of the cells’ natural robust reparative function. EPC, endothelial precursor cell I/R, ischemia/reperfusion LSCM, laser scanning confocal microscope OIR, oxygen-induced retinopathy SDF, stromal-derived factor STZ, streptozotocin VEGF, vascular endothelial growth factor Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted December 25, 2006. Received September 6, 2006. DIABETES
AbstractList Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded in diabetes. We previously demonstrated that EPCs isolated from diabetic patients have a profound inability to migrate in vitro. We asked whether EPCs from normal individuals are better able to repopulate degenerate (acellular) retinal capillaries in chronic (diabetes) and acute (ischemia/reperfusion [I/R] injury and neonatal oxygen-induced retinopathy [OIR]) animal models of ocular vascular damage. Streptozotocin-induced diabetic mice, spontaneously diabetic BBZDR/Wor rats, adult mice with I/R injury, or neonatal mice with OIR were injected within the vitreous or the systemic circulation with fluorescently labeled CD34+ cells from either diabetic patients or age- and sex-matched healthy control subjects. At specific times after administering the cells, the degree of vascular repair of the acellular capillaries was evaluated immunohistologically and quantitated. In all four models, healthy human (hu)CD34+ cells attached and assimilated into vasculature, whereas cells from diabetic donors uniformly were unable to integrate into damaged vasculature. These studies demonstrate that healthy huCD34+ cells can effectively repair injured retina and that there is defective repair of vasculature in patients with diabetes. Defective EPCs may be amenable to pharmacological manipulation and restoration of the cells’ natural robust reparative function.
Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded in diabetes. We previously demonstrated that EPCs isolated from diabetic patients have a profound inability to migrate in vitro. We asked whether EPCs from normal individuals are better able to repopulate degenerate (acellular) retinal capillaries in chronic (diabetes) and acute (ischemia/reperfusion [I/R] injury and neonatal oxygen-induced retinopathy [OIR]) animal models of ocular vascular damage. Streptozotocin-induced diabetic mice, spontaneously diabetic BBZDR/Wor rats, adult mice with I/R injury, or neonatal mice with OIR were injected within the vitreous or the systemic circulation with fluorescently labeled CD[34.sup.+] cells from either diabetic patients or age-and sex-matched healthy control subjects. At specific times after administering the cells, the degree of vascular repair of the acellular capillaries was evaluated immunohistologically and quantitated. In all four models, healthy human (hu)CD[34.sup.+] cells attached and assimilated into vasculature, whereas cells from diabetic donors uniformly were unable to integrate into damaged vasculature. These studies demonstrate that healthy huCD[34.sup.+] cells can effectively repair injured retina and that there is defective repair of vasculature in patients with diabetes. Defective EPCs may be amenable to pharmacological manipulation and restoration of the cells' natural robust reparative function.
Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded in diabetes. We previously demonstrated that EPCs isolated from diabetic patients have a profound inability to migrate in vitro. We asked whether EPCs from normal individuals are better able to repopulate degenerate (acellular) retinal capillaries in chronic (diabetes) and acute (ischemia/reperfusion [I/R] injury and neonatal oxygen-induced retinopathy [OIR]) animal models of ocular vascular damage. Streptozotocin-induced diabetic mice, spontaneously diabetic BBZDR/Wor rats, adult mice with I/R injury, or neonatal mice with OIR were injected within the vitreous or the systemic circulation with fluorescently labeled CD34(+) cells from either diabetic patients or age- and sex-matched healthy control subjects. At specific times after administering the cells, the degree of vascular repair of the acellular capillaries was evaluated immunohistologically and quantitated. In all four models, healthy human (hu)CD34(+) cells attached and assimilated into vasculature, whereas cells from diabetic donors uniformly were unable to integrate into damaged vasculature. These studies demonstrate that healthy huCD34(+) cells can effectively repair injured retina and that there is defective repair of vasculature in patients with diabetes. Defective EPCs may be amenable to pharmacological manipulation and restoration of the cells' natural robust reparative function.Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded in diabetes. We previously demonstrated that EPCs isolated from diabetic patients have a profound inability to migrate in vitro. We asked whether EPCs from normal individuals are better able to repopulate degenerate (acellular) retinal capillaries in chronic (diabetes) and acute (ischemia/reperfusion [I/R] injury and neonatal oxygen-induced retinopathy [OIR]) animal models of ocular vascular damage. Streptozotocin-induced diabetic mice, spontaneously diabetic BBZDR/Wor rats, adult mice with I/R injury, or neonatal mice with OIR were injected within the vitreous or the systemic circulation with fluorescently labeled CD34(+) cells from either diabetic patients or age- and sex-matched healthy control subjects. At specific times after administering the cells, the degree of vascular repair of the acellular capillaries was evaluated immunohistologically and quantitated. In all four models, healthy human (hu)CD34(+) cells attached and assimilated into vasculature, whereas cells from diabetic donors uniformly were unable to integrate into damaged vasculature. These studies demonstrate that healthy huCD34(+) cells can effectively repair injured retina and that there is defective repair of vasculature in patients with diabetes. Defective EPCs may be amenable to pharmacological manipulation and restoration of the cells' natural robust reparative function.
Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells Sergio Caballero 1 , Nilanjana Sengupta 1 , Aqeela Afzal 1 , Kyung-Hee Chang 1 , Sergio Li Calzi 1 , Dennis L. Guberski 2 , Timothy S. Kern 3 and Maria B. Grant 1 1 Program in Stem Cell Biology, Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 2 Biomedical Research Models, Worcester, Massachusetts 3 Department of Medicine, Case Western Reserve University, Cleveland, Ohio Address correspondence and reprint requests to Maria B. Grant, MD, Pharmacology and Therapeutics, University of Florida, P.O. Box 100267, Gainesville, FL 32610-0267. E-mail: grantma{at}pharmacology.ufl.edu Abstract Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded in diabetes. We previously demonstrated that EPCs isolated from diabetic patients have a profound inability to migrate in vitro. We asked whether EPCs from normal individuals are better able to repopulate degenerate (acellular) retinal capillaries in chronic (diabetes) and acute (ischemia/reperfusion [I/R] injury and neonatal oxygen-induced retinopathy [OIR]) animal models of ocular vascular damage. Streptozotocin-induced diabetic mice, spontaneously diabetic BBZDR/Wor rats, adult mice with I/R injury, or neonatal mice with OIR were injected within the vitreous or the systemic circulation with fluorescently labeled CD34 + cells from either diabetic patients or age- and sex-matched healthy control subjects. At specific times after administering the cells, the degree of vascular repair of the acellular capillaries was evaluated immunohistologically and quantitated. In all four models, healthy human (hu)CD34 + cells attached and assimilated into vasculature, whereas cells from diabetic donors uniformly were unable to integrate into damaged vasculature. These studies demonstrate that healthy huCD34 + cells can effectively repair injured retina and that there is defective repair of vasculature in patients with diabetes. Defective EPCs may be amenable to pharmacological manipulation and restoration of the cells’ natural robust reparative function. EPC, endothelial precursor cell I/R, ischemia/reperfusion LSCM, laser scanning confocal microscope OIR, oxygen-induced retinopathy SDF, stromal-derived factor STZ, streptozotocin VEGF, vascular endothelial growth factor Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted December 25, 2006. Received September 6, 2006. DIABETES
Audience Professional
Author Aqeela Afzal
Sergio Caballero
Nilanjana Sengupta
Kyung-Hee Chang
Sergio Li Calzi
Maria B. Grant
Dennis L. Guberski
Timothy S. Kern
AuthorAffiliation 1 Program in Stem Cell Biology, Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida
3 Department of Medicine, Case Western Reserve University, Cleveland, Ohio
2 Biomedical Research Models, Worcester, Massachusetts
AuthorAffiliation_xml – name: 3 Department of Medicine, Case Western Reserve University, Cleveland, Ohio
– name: 1 Program in Stem Cell Biology, Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida
– name: 2 Biomedical Research Models, Worcester, Massachusetts
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  organization: Program in Stem Cell Biology, Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida
– sequence: 2
  givenname: Nilanjana
  surname: Sengupta
  fullname: Sengupta, Nilanjana
  organization: Program in Stem Cell Biology, Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida
– sequence: 3
  givenname: Aqeela
  surname: Afzal
  fullname: Afzal, Aqeela
  organization: Program in Stem Cell Biology, Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida
– sequence: 4
  givenname: Kyung-Hee
  surname: Chang
  fullname: Chang, Kyung-Hee
  organization: Program in Stem Cell Biology, Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida
– sequence: 5
  givenname: Sergio
  surname: Li Calzi
  fullname: Li Calzi, Sergio
  organization: Program in Stem Cell Biology, Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida
– sequence: 6
  givenname: Dennis L.
  surname: Guberski
  fullname: Guberski, Dennis L.
  organization: Biomedical Research Models, Worcester, Massachusetts
– sequence: 7
  givenname: Timothy S.
  surname: Kern
  fullname: Kern, Timothy S.
  organization: Department of Medicine, Case Western Reserve University, Cleveland, Ohio
– sequence: 8
  givenname: Maria B.
  surname: Grant
  fullname: Grant, Maria B.
  organization: Program in Stem Cell Biology, Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida
BackLink http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18678894$$DView record in Pascal Francis
https://www.ncbi.nlm.nih.gov/pubmed/17395742$$D View this record in MEDLINE/PubMed
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Issue 4
Keywords Endocrinopathy
Endothelial cell
Ischemia
Diabetes mellitus
Precursor cell
Cardiovascular disease
Repair
Language English
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Snippet Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells Sergio Caballero 1 , Nilanjana Sengupta 1 , Aqeela Afzal 1...
Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded in diabetes. We previously demonstrated...
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SubjectTerms Acute Disease
Analysis
Animals
Antigens, CD - blood
Antigens, CD34 - blood
Biological and medical sciences
Blood vessels
Cell Transplantation
Chronic Disease
Diabetes
Diabetes Mellitus, Experimental - therapy
Diabetes. Impaired glucose tolerance
Diabetic Angiopathies - therapy
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Endothelial growth factors
Endothelium, Vascular - transplantation
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Female
Genetic aspects
Humans
Ischemia
Ischemia - therapy
Laboratories
Localization
Male
Medical sciences
Mice
Mice, Inbred C57BL
Ostomy
Peripheral vascular diseases
Rats
Rats, Inbred Strains
Retinal Vessels - injuries
Vascular endothelial growth factor
Title Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells
URI http://diabetes.diabetesjournals.org/content/56/4/960.abstract
https://www.ncbi.nlm.nih.gov/pubmed/17395742
https://www.proquest.com/docview/216484457
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https://pubmed.ncbi.nlm.nih.gov/PMC3746188
Volume 56
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