Circulating mononuclear progenitor cells: Differential roles for subpopulations in repair of retinal vascular injury

Sergio Caballero, Sugata Hazra, Ashay Bhatwadekar, Sergio Li Calzi, Linda J. Paradiso, Leonard P. Miller, Lung Ji Chang, Timothy S. Kern, Maria B. Grant

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

PURPOSE. We examined effect on retinal vascular homing of exogenous CD34+ and CD14+ progenitor cells using mouse models of chronic (streptozotocin [STZ]-induced diabetes) and acute (ischemia-reperfusion [I/R]) ocular vascular injury. METHODS. STZ-treated mice of short or long duration (≤4, ≥11 months) diabetes, along with age- and sex-matched controls, were given intravitreous injections of human CD34+ and CD14+ cells isolated from healthy or diabetic donors alone or in combination. I/R injured mice were given diabetic or nondiabetic CD34+ cells with mesenchymal stem cells (MSCs) or diabetic CD34+ cells manipulated by ex vivo fucosylation with ASC-101. Injected cells were localized by fluorescent immunocytochemistry, and the degree of retinal vascular colocalization quantified morphometrically. Permeability was assessed by fluorescent albumin leakage. RESULTS. Diabetic CD14+ cells associated with vessels to a greater degree than diabetic CD34+ cells. Vascular permeability was reduced only by nondiabetic cells and only at the highest number of cells tested. Diabetic CD34+ cells consistently demonstrated reduced migration. There was a 2-fold or 4-fold increase over control in the specific localization of diabetic CD34+ cells within the vasculature when these cells were co-administered with MSCs or ex vivo fucosylated prior to injection, respectively. CONCLUSIONS. Diabetic CD14+ cells, unlike diabetic CD34+ cells, retain robust homing characteristics. CD34+ or CD14+ subsets rather than whole bone marrow or peripheral blood cells may prove more beneficial in autologous cell therapy for diabetics. Co-administration with MSCs or ex vivo fucosylation may enhance utility of CD34+ cells in cell therapy for diabetic ocular conditions like macular ischemia and retinal nonperfusion.

Original languageEnglish (US)
Pages (from-to)3000-3009
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number4
DOIs
StatePublished - 2013
Externally publishedYes

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Retinal Vessels
Vascular System Injuries
Stem Cells
Mesenchymal Stromal Cells
Ischemia
Cell- and Tissue-Based Therapy
Reperfusion
Eye Injuries
Injections
Experimental Diabetes Mellitus
Capillary Permeability
Streptozocin
Albumins
Permeability
Blood Cells

Keywords

  • Diabetic retinopathy
  • Neovascularization
  • Progenitor cells

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Circulating mononuclear progenitor cells : Differential roles for subpopulations in repair of retinal vascular injury. / Caballero, Sergio; Hazra, Sugata; Bhatwadekar, Ashay; Li Calzi, Sergio; Paradiso, Linda J.; Miller, Leonard P.; Chang, Lung Ji; Kern, Timothy S.; Grant, Maria B.

In: Investigative Ophthalmology and Visual Science, Vol. 54, No. 4, 2013, p. 3000-3009.

Research output: Contribution to journalArticle

Caballero, Sergio ; Hazra, Sugata ; Bhatwadekar, Ashay ; Li Calzi, Sergio ; Paradiso, Linda J. ; Miller, Leonard P. ; Chang, Lung Ji ; Kern, Timothy S. ; Grant, Maria B. / Circulating mononuclear progenitor cells : Differential roles for subpopulations in repair of retinal vascular injury. In: Investigative Ophthalmology and Visual Science. 2013 ; Vol. 54, No. 4. pp. 3000-3009.
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TY - JOUR

T1 - Circulating mononuclear progenitor cells

T2 - Differential roles for subpopulations in repair of retinal vascular injury

AU - Caballero, Sergio

AU - Hazra, Sugata

AU - Bhatwadekar, Ashay

AU - Li Calzi, Sergio

AU - Paradiso, Linda J.

AU - Miller, Leonard P.

AU - Chang, Lung Ji

AU - Kern, Timothy S.

AU - Grant, Maria B.

PY - 2013

Y1 - 2013

N2 - PURPOSE. We examined effect on retinal vascular homing of exogenous CD34+ and CD14+ progenitor cells using mouse models of chronic (streptozotocin [STZ]-induced diabetes) and acute (ischemia-reperfusion [I/R]) ocular vascular injury. METHODS. STZ-treated mice of short or long duration (≤4, ≥11 months) diabetes, along with age- and sex-matched controls, were given intravitreous injections of human CD34+ and CD14+ cells isolated from healthy or diabetic donors alone or in combination. I/R injured mice were given diabetic or nondiabetic CD34+ cells with mesenchymal stem cells (MSCs) or diabetic CD34+ cells manipulated by ex vivo fucosylation with ASC-101. Injected cells were localized by fluorescent immunocytochemistry, and the degree of retinal vascular colocalization quantified morphometrically. Permeability was assessed by fluorescent albumin leakage. RESULTS. Diabetic CD14+ cells associated with vessels to a greater degree than diabetic CD34+ cells. Vascular permeability was reduced only by nondiabetic cells and only at the highest number of cells tested. Diabetic CD34+ cells consistently demonstrated reduced migration. There was a 2-fold or 4-fold increase over control in the specific localization of diabetic CD34+ cells within the vasculature when these cells were co-administered with MSCs or ex vivo fucosylated prior to injection, respectively. CONCLUSIONS. Diabetic CD14+ cells, unlike diabetic CD34+ cells, retain robust homing characteristics. CD34+ or CD14+ subsets rather than whole bone marrow or peripheral blood cells may prove more beneficial in autologous cell therapy for diabetics. Co-administration with MSCs or ex vivo fucosylation may enhance utility of CD34+ cells in cell therapy for diabetic ocular conditions like macular ischemia and retinal nonperfusion.

AB - PURPOSE. We examined effect on retinal vascular homing of exogenous CD34+ and CD14+ progenitor cells using mouse models of chronic (streptozotocin [STZ]-induced diabetes) and acute (ischemia-reperfusion [I/R]) ocular vascular injury. METHODS. STZ-treated mice of short or long duration (≤4, ≥11 months) diabetes, along with age- and sex-matched controls, were given intravitreous injections of human CD34+ and CD14+ cells isolated from healthy or diabetic donors alone or in combination. I/R injured mice were given diabetic or nondiabetic CD34+ cells with mesenchymal stem cells (MSCs) or diabetic CD34+ cells manipulated by ex vivo fucosylation with ASC-101. Injected cells were localized by fluorescent immunocytochemistry, and the degree of retinal vascular colocalization quantified morphometrically. Permeability was assessed by fluorescent albumin leakage. RESULTS. Diabetic CD14+ cells associated with vessels to a greater degree than diabetic CD34+ cells. Vascular permeability was reduced only by nondiabetic cells and only at the highest number of cells tested. Diabetic CD34+ cells consistently demonstrated reduced migration. There was a 2-fold or 4-fold increase over control in the specific localization of diabetic CD34+ cells within the vasculature when these cells were co-administered with MSCs or ex vivo fucosylated prior to injection, respectively. CONCLUSIONS. Diabetic CD14+ cells, unlike diabetic CD34+ cells, retain robust homing characteristics. CD34+ or CD14+ subsets rather than whole bone marrow or peripheral blood cells may prove more beneficial in autologous cell therapy for diabetics. Co-administration with MSCs or ex vivo fucosylation may enhance utility of CD34+ cells in cell therapy for diabetic ocular conditions like macular ischemia and retinal nonperfusion.

KW - Diabetic retinopathy

KW - Neovascularization

KW - Progenitor cells

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