Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization

Grant, Maria B.; May, W. Stratford; Caballero, Sergio; Brown, Gary A. J.; Guthrie, Steven M.; Mames, Robert N.; Byrne, Barry; Vaught, Timothy; Spoerri, P.E.; Peck, Ammon B.; Scott, Edward W.

doi:10.1038/nm0602-607

Cited by 614 publications

(490 citation statements)

References 35 publications

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“…Bone-marrow-derived cells have been shown to incorporate sparsely in the endothelium of "normal" blood vessels, reflecting a contribution to physiological endothelial cell turnover, significantly in neovasculature associated with hindlimb ischemia, myocardial infarction, corneal injury, retinal ischemia, cutaneous wounds, grafted aorta segments, and tumor growth. 17,[31][32][33] Few studies have addressed the origin of the renal vasculature. In the past there have been sparse and conflicting reports on the presence of host endothelial cells in kidney allografts.…”

Section: Discussionmentioning

confidence: 99%

Bone-Marrow-Derived Cells Contribute to Glomerular Endothelial Repair in Experimental Glomerulonephritis

Rookmaaker

Smits

Tolboom

et al. 2003

The American Journal of Pathology

160

122

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Glomerular endothelial injury plays an important role in the pathogenesis of renal diseases and is centrally involved in renal disease progression. Glomerular endothelial repair may help maintain renal function. We examined whether bone-marrow (BM)-derived cells contribute to glomerular repair. A rat allogenic BM transplant model was used to allow tracing of BM-derived cells using a donor major histocompatibility complex class-I specific mAb. In glomeruli of chimeric rats we identified a small number of donor-BM-derived endothelial and mesangial cells, which increased in a time-dependent manner. Induction of anti-Thy-1.1-glomerulonephritis (transient mesangial and secondary glomerular endothelial injury) caused a significant, more than fourfold increase in the number of BM-derived glomerular endothelial cells at day 7 after anti-Thy-1.1 injection compared to chimeric rats without glomerular injury. The level of BM-derived endothelial cells remained high at day 28. We also observed a more than sevenfold increase in the number of BM-derived mesangial cells at day 28. BM-derived endothelial and mesangial cells were fully integrated in the glomerular structure. Our data show that BM-derived cells participate in glomerular endothelial and mesangial cell turnover and contribute to microvascular repair. These findings provide novel insights into the pathogenesis of renal disease and suggest a potential role for stem cell therapy.

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Section: Discussionmentioning

confidence: 99%

Bone-Marrow-Derived Cells Contribute to Glomerular Endothelial Repair in Experimental Glomerulonephritis

Rookmaaker

Smits

Tolboom

et al. 2003

The American Journal of Pathology

160

122

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“…Studies in a mouse model of diabetes showed impairment of vasculogenesis in response to hind limb ischemia (Schatteman et al, 2000). Studies in a model of ischemic retinopathy have shown that bone marrow-derived hematopoietic stem cells participate in retinal neovascularization (Grant et al, 2002). Investigations using cell-based gene therapy in the mouse OIR model showed that these cells can rescue and stabilize degenerating vessels, and the cells can inhibit new vessel formation in a mouse model of retinal degeneration (Otani et al, 2002).…”

Section: Vegf and Retinalmentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

615

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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“…It has been reported that marrow-derived endothelial progenitor cells contribute to adult vasculogenesis (Tamura et al, 2004) and tumour angiogenesis (Rafii et al, 2002;Peters et al, 2005) by circulating through the vascular system and incorporating into the wall of newly formed vessels (Marchetti et al, 2002;Rafii and Lyden, 2003). Evidence that vasculogenesis is involved in neovascularisation has been found in studies on tumour vessels (Reyes et al, 2002), experimental retinopathy (Grant et al, 2002;Tomita et al, 2004;Butler et al, 2005), myocardial ischaemia (Kocher et al, 2001(Kocher et al, , 2006Botta et al, 2004), wound healing Crisa et al, 1999), and hindlimb ischaemia Kalka et al, 2000;Iwaguro et al, 2002). An important question that remains unanswered by the literature is whether circulating endothelial progenitor cells per se or their differentiated progeny are incorporated into the vascular wall .…”

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confidence: 99%

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

et al. 2007

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Angiogenesis and post-natal vasculogenesis are two processes involved in the formation of new vessels, and both are essential for tumour growth and metastases. We isolated endothelial cells from human blood mononuclear cells by selective culture. These blood outgrowth cells expressed endothelial cell markers and responded correctly to functional assays. To evaluate the potential of blood outgrowth endothelial cells (BOECs) to construct functional vessels in vivo, NOD-SCID mice were implanted with Lewis lung carcinoma cells subcutaneously (s.c.). Blood outgrowth endothelial cells were then injected through the tail vein. Initial distribution of these cells occurred throughout the lung, liver, spleen, and tumour vessels, but they were only found in the spleen, liver, and tumour tissue 48 h after injection. By day 24, they were mainly found in the tumour vasculature. Tumour vessel counts were also increased in mice receiving BOEC injections as compared to saline injections. We engineered BOECs to deliver an angiogenic inhibitor directly to tumour endothelium by transducing them with the gene for human endostatin. These cells maintained an endothelial phenotype and decreased tumour vascularisation and tumour volume in mice. We conclude that BOECs have the potential for tumour-specific delivery of cancer gene therapy.

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Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization

Cited by 614 publications

References 35 publications

Bone-Marrow-Derived Cells Contribute to Glomerular Endothelial Repair in Experimental Glomerulonephritis

Bone-Marrow-Derived Cells Contribute to Glomerular Endothelial Repair in Experimental Glomerulonephritis

Vascular endothelial growth factor in eye disease

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

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