Umbilical cord blood-selected CD133+ cells exhibit vasculogenic functionality in vitro and in vivo

Finney, Marcie; Fanning, Laura R.; Joseph, Matthew; Goldberg, Jonathan; Greco, Nicholas J.; Bhakta, Shyam; Winter, Daniel; Forster, Margaret; Scheid, Paul; Sabe, Marwa; Pompili, Vincent J.; Laughlin, Mary J.

doi:10.3109/14653240903300658

Cited by 17 publications

(8 citation statements)

References 27 publications

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“…Here we show that as expected, transduced EPCs carrying hNIS gene migrated and homed to the sites of tumors. Immunohistochemistry also indicated that these EPCs migrated and incorporated into tumor angiogenesis/vasculogenesis that was in accordance with now well established evidence that EPCs are involved in both vasculogenic and angiogenic processes [18], [20], [22], [23]. Transduced EPCs also expressed functional gene product that resulted in intracellular uptake of Tc-99m through trans-genetically expressed hNIS channel which was detected by in vivo SPECT.…”

Section: Discussionsupporting

confidence: 85%

“…Numerous previous publications, as well as our own reports, indicated the important role of cord blood or peripheral blood derived CD133 + EPCs in neo-vasculo- as well as angiogenesis associated with tumors or ischemic lesions [6], [18], [19]. Migration and homing of exogenously administered or bone marrow mobilized endogenous EPCs to tumor or ischemic lesions are dependent on the expression of stromal derived factor (SDF-1) [6], [20], [21].…”

Section: Discussionmentioning

confidence: 83%

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Endothelial Progenitor Cells (EPCs) as Gene Carrier System for Rat Model of Human Glioma

et al. 2012

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BackgroundDue to their unique property to migrate to pathological lesions, stem cells are used as a delivery vehicle for therapeutic genes to tumors, especially for glioma. It is critically important to track the movement, localization, engraftment efficiency and functional capability or expression of transgenes of selected cell populations following transplantation. The purposes of this study were to investigate whether 1) intravenously administered, genetically transformed cord blood derived EPCs can carry human sodium iodide symporter (hNIS) to the sites of tumors in rat orthotopic model of human glioma and express transgene products, and 2) whether accumulation of these administered EPCs can be tracked by different in vivo imaging modalities.Methods and ResultsCollected EPCs were cultured and transduced to carry hNIS. Cellular viability, differential capacity and Tc-99m uptake were determined. Five to ten million EPCs were intravenously administered and Tc-99-SPECT images were acquired on day 8, to determine the accumulation of EPCs and expression of transgenes (increase activity of Tc-99m) in the tumors. Immunohistochemistry was performed to determine endothelial cell markers and hNIS positive cells in the tumors. Transduced EPCs were also magnetically labeled and accumulation of cells was confirmed by MRI and histochemistry. SPECT analysis showed increased activity of Tc-99m in the tumors that received transduced EPCs, indicative of the expression of transgene (hNIS). Activity of Tc-99m in the tumors was also dependent on the number of administered transduced EPCs. MRI showed the accumulation of magnetically labeled EPCs. Immunohistochemical analysis showed iron and hNIS positive and, human CD31 and vWF positive cells in the tumors.ConclusionEPC was able to carry and express hNIS in glioma following IV administration. SPECT detected migration of EPCs and expression of the hNIS gene. EPCs can be used as gene carrier/delivery system for glioma therapy as well as imaging probes.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 83%

Endothelial Progenitor Cells (EPCs) as Gene Carrier System for Rat Model of Human Glioma

et al. 2012

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“…EPC targeting to sites of neovascularisation involves their migration, adhesion, and differentiation into mature endothelial cells [5,6]. Various cell populations play a role in angiogenesis [7,8], but only one subset, endothelial colonyforming cells (ECFC), has been shown to possess all of the characteristics of a true endothelial progenitor capable of forming neovessels in vivo [9].…”

Section: Introductionmentioning

confidence: 99%

A motif within the N-terminal domain of TSP-1 specifically promotes the proangiogenic activity of endothelial colony-forming cells

Dias

Benslimane-Ahmim

Egot

et al. 2012

Biochemical Pharmacology

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Thrombospondin-1 (TSP-1) gives rise to fragments that have both pro-and anti-angiogenic effects in vitro and in vivo. The TSP-HepI peptide (2.3 kDa), located in the N-terminal domain of TSP-1, has proangiogenic effects on endothelial cells. We have previously shown that TSP-1 itself exhibits a dual effect on endothelial colony-forming cells (ECFC) by enhancing their adhesion through its TSP-HepI fragment while reducing their proliferation and differentiation into vascular tubes (tubulogenesis) in vitro. This effect is likely mediated through CD47 binding to the TSP-1 C-terminal domain. Here we investigated the effect of TSP-HepI peptide on the angiogenic properties of ECFC in vitro and in vivo. TSP-HepI peptide potentiated FGF-2-induced neovascularisation by enhancing ECFC chemotaxis and tubulogenesis in a Matrigel plug assay. ECFC exposure to 20 mg/mL of TSP-HepI peptide for 18 h enhanced cell migration (p < 0.001 versus VEGF exposure), upregulated alpha 6-integrin expression, and enhanced their cell adhesion to activated endothelium under physiological shear stress conditions at levels comparable to those of SDF-1a. The adhesion enhancement appeared to be mediated by the heparan sulfate proteoglycan (HSPG) syndecan-4, as ECFC adhesion was significantly reduced by a syndecan-4-neutralising antibody. ECFC migration and tubulogenesis were stimulated neither by a TSP-HepI peptide with a modified heparin-binding site (S/TSP-HepI) nor when the glycosaminoglycans (GAGs) moieties were removed from the ECFC surface by enzymatic treatment. Ex vivo TSP-HepI priming could potentially serve to enhance the effectiveness of therapeutic neovascularisation with ECFC.

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“…CD133(+) cells have been introduced as a possible cell therapeutic for the treatment of ischemic conditions [34], but so far these cells have not been considered as a new therapy option in the context of bone injury.…”

Section: Discussionmentioning

confidence: 99%

CD133: Enhancement of Bone Healing by Local Transplantation of Peripheral Blood Cells in a Biologically Delayed Rat Osteotomy Model

et al. 2013

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Sufficient angiogenesis is crucial during tissue regeneration and therefore also pivotal in bone defect healing. Recently, peripheral blood derived progenitor cells have been identified to have in addition to their angiogenic potential also osteogenic characteristics, leading to the hypothesis that bone regeneration could be stimulated by local administration of these cells. The aim of this study was to evaluate the angiogenic potential of locally administered progenitor cells to improve bone defect healing. Cells were separated from the peripheral blood of donor animals using the markers CD34 and CD133. Results of the in vitro experiments confirmed high angiogenic potential in the CD133(+) cell group. CD34(+) and CD133(+) cells were tested in an in vivo rat femoral defect model of delayed healing for their positive effect on the healing outcome. An increased callus formation and higher bone mineral density of callus tissue was found after the CD133(+) cell treatment compared to the group treated with CD34(+) cells and the control group without cells. Histological findings confirmed an increase in vessel formation and mineralization at day 42 in the osteotomy gap after CD133(+) cell transplantation. The higher angiogenic potential of CD133(+) cells from the in vitro experients therefore correlates with the in vivo data. This study demonstrates the suitability of angiogenic precursors to further bone healing and gives an indication that peripheral blood is a promising source for progenitor cells circumventing the problems associated with bone marrow extraction.

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Umbilical cord blood-selected CD133+ cells exhibit vasculogenic functionality in vitro and in vivo

Cited by 17 publications

References 27 publications

Endothelial Progenitor Cells (EPCs) as Gene Carrier System for Rat Model of Human Glioma

Endothelial Progenitor Cells (EPCs) as Gene Carrier System for Rat Model of Human Glioma

A motif within the N-terminal domain of TSP-1 specifically promotes the proangiogenic activity of endothelial colony-forming cells

CD133: Enhancement of Bone Healing by Local Transplantation of Peripheral Blood Cells in a Biologically Delayed Rat Osteotomy Model

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