Recruitment Of Endothelial Precursor Cells Research Articles

The role of vasculature and angiogenesis in respiratory diseases.

In European countries, nearly 10% of all hospital admissions are related to respiratory diseases, mainly chronic life-threatening diseases such as COPD, pulmonary hypertension, IPF or lung cancer. The contribution of blood vessels and angiogenesis to lung regeneration, remodeling and disease progression has been increasingly appreciated. The vascular supply of the lung shows the peculiarity of dual perfusion of the pulmonary circulation (vasa publica), which maintains a functional blood-gas barrier, and the bronchial circulation (vasa privata), which reveals a profiled capacity for angiogenesis (namely intussusceptive and sprouting angiogenesis) and alveolar-vascular remodeling by the recruitment of endothelial precursor cells. The aim of this review is to outline the importance of vascular remodeling and angiogenesis in a variety of non-neoplastic and neoplastic acute and chronic respiratory diseases such as lung infection, COPD, lung fibrosis, pulmonary hypertension and lung cancer.

Vascular co-option in resistance to anti-angiogenic therapy.

Three different mechanisms of neovascularization have been described in tumor growth, including sprouting angiogenesis, intussusceptive microvascular growth and glomeruloid vascular proliferation. Tumors can also grow by means of alternative mechanisms including vascular co-option, vasculogenic mimicry, angiotropism, and recruitment of endothelial precursor cells. Vascular co-option occurs in tumors independently of sprouting angiogenesis and the non-angiogenic cancer cells are described as exploiting pre-existing vessels. Vascular co-option is more frequently observed in tumors of densely vascularized organs, including the brain, lung and liver, and vascular co-option represents one of the main mechanisms involved in metastasis, as occurs in liver and lung, and resistance to anti-angiogenic therapy. The aim of this review article is to analyze the role of vascular co-option as mechanism through which tumors develop resistance to anti-angiogenic conventional therapeutic approaches and how blocking co-option can suppress tumor growth.

Glycol Chitosan Engineered Autoregenerative Antioxidant Significantly Attenuates Pathological Damages in Models of Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the foremost cause of irreversible blindness in people over the age of 65 especially in developing countries. Therefore, an exploration of effective and alternative therapeutic interventions is an unmet medical need. It has been established that oxidative stress plays a key role in the pathogenesis of AMD, and hence, neutralizing oxidative stress is an effective therapeutic strategy for treatment of this serious disorder. Owing to autoregenerative properties, nanoceria has been widely used as a nonenzymatic antioxidant in the treatment of oxidative stress related disorders. Yet, its potential clinical implementation has been greatly hampered by its poor water solubility and lack of reliable tracking methodologies/processes and hence poor absorption, distribution, and targeted delivery. The water solubility and surface engineering of a drug with biocompatible motifs are fundamental to pharmaceutical products and precision medicine. Here, we report an engineered water-soluble, biocompatible, trackable nanoceria with enriched antioxidant activity to scavenge intracellular reactive oxygen species (ROS). Experimental studies with in vitro and in vivo models demonstrated that this antioxidant is autoregenerative and more active in inhibiting laser-induced choroidal neovascularization by decreasing ROS-induced pro-angiogenic vascular endothelial growth factor (VEGF) expression, cumulative oxidative damage, and recruitment of endothelial precursor cells without exhibiting any toxicity. This advanced formulation may offer a superior therapeutic effect to deal with oxidative stress induced pathogeneses, such as AMD.

Neovascularization After Irradiation: What is the Source of Newly Formed Vessels in Recurring Tumors?

Local relapse of tumors after radiation therapy remains a challenge in oncology. To devise rational approaches for preventing this relapse, we have to improve our understanding of how new vessels form in previously irradiated tumors. We propose that tumor regrowth after local irradiation is dependent on blood vessel formation by local endothelial cells without the need for recruitment of endothelial precursor cells from distant nonirradiated tissues or bone marrow. We also suggest that infiltrating myeloid bone marrow-derived cells promote survival of local endothelial cells during the early period after irradiation and angiogenesis during the later stage of tumor regrowth, both via paracrine mechanisms.

Preventing and repairing vascular damage in scleroderma: Should we focus beyond vasodilatation to recruitment of endothelial precursor cells?

Preventing and repairing vascular damage in scleroderma: Should we focus beyond vasodilatation to recruitment of endothelial precursor cells?

ACE inhibitors and statins for bone marrow failure following myocardial infarction?

See article by Thum et al. [4] (pages 50–60) in this issue . Since their initial description a decade ago, endothelial precursor cells (EPCs) have been intensively studied, especially in relation to vascular injury or pathology and their clinical consequences. However, there is no consensus on the precise phenotypic definition of EPCs. Nonetheless, it has been established that these EPCs contribute to neovascularization in a variety of tissues [1] and they may even play a role in tissue regeneration if they transdifferentiate and integrate into functional tissue, for instance myocardium. The latter, however, is highly controversial. Recruitment of EPCs from the bone marrow appears to be a natural mechanism to restore vascular function or even tissue function. Many acute tissue injuries, including myocardial infarction (MI), lead to a transient rise in circulating EPCs [2]. The functional importance of this rise in EPCs after MI is suggested by a correlation with better prognosis through reduced incidence of cardiac failure or death from cardiac cause. Multiple mechanisms have been described for this presumed interaction between peripheral organs and the bone marrow, mostly involving circulating factors such as VEGF [2] and perhaps CSFs [3]. It is therefore surprising that … * Corresponding author. Tel.: +31 43 3881200; fax: +31 43 3884166. Email address: m.post{at}fys.unimaas.nl

Efficacy of systemic administration of SDF-1 in a model of vascular insufficiency: Support for an endothelium-dependent mechanism

Studies have reported that administration of stromal cell-derived factor-1 (SDF-1), the ligand for the G-protein coupled receptor CXCR4, increased collateral blood flow in a mouse model of vascular insufficiency via recruitment of endothelial precursor cells (EPC). The present study investigated the contribution of mature endothelial cells in the actions of SDF-1. The regulation of SDF-1 and CXCR4 was examined in the rat cornea cauterization (CC) and aortic ring (AR) model. The functional significance of the SDF-1/CXCR4 pathway was explored in cultured endothelial cells, the AR model, and on collateral blood flow in a rat model of vascular insufficiency. In the present study, the CXCR4 transcript was dramatically upregulated in the rat CC and AR explants, systems containing and lacking bone marrow-derived EPCs, respectively. Addition of AMD3100, a selective CXCR4 antagonist, had no effect on vessel growth in the AR alone, but completely inhibited SDF-1 mediated increases in vascular sprouting. In cultured endothelial cells, SDF-1 alone or in combination with vascular endothelial growth factor (VEGF) significantly enhanced cell survival and migration. Finally, systemic administration of SDF-1 in a rat model of arterial insufficiency enhanced collateral blood flow above vehicle control and equal to that of VEGF after 2 weeks of treatment. These studies support activation of the SDF-1/CXCR4 axis as a means to promote blood vessel growth and enhance collateral blood flow, at least in part, via direct effects on vascular endothelial cells.

Coevolution of cancer and stromal cellular responses

It is now becoming apparent that multiple types of stromal cells, including macrophages, mast cells, adipocytes, and fibroblasts make pivotal contributions to carcinogenesis. In the May 6 issue of Cell, Orimo and colleagues (Orimo et al., 2005) show that carcinoma-associated fibroblasts can promote epithelial tumorigenesis by secreting the chemokine SDF-1alpha (CXCL12). SDF-1alpha stimulates carcinoma cell proliferation and recruitment of endothelial precursor cells.

Breast tumors induce the recruitment of AC133+KDR+ endothelial precursor cells mobilized by plasma vascular endothelial growth factor

Recent evidence has demonstrated the importance of bone marrow-derived endothelial precursor cells (EPC) in the contribution to postnatal physiological and pathological neovascularization, and in tumor growth and angiogenesis. These cells are recruited undifferentiated; in response to systemic or chemoattractive signals, such as vascular endothelial growth factor (VEGF), they lodge in the growing or lesioned tissue and differentiate into endothelial cells in response to local stimuli and cell–cell interactions. The extent and the significance of the EPC contribution for the growing of most tumors, including breast carcinomas, are still not defined. We analysed the peripheral blood mononuclear cells (PBMNC) of 48 breast cancer patients and found that 16.7% of them have circulating EPC. These cells were detected by RT-PCR expression of AC133 and kinase domain receptor (KDR). Furthermore, using an ELISA assay, we also found an association between circulating AC133+KDR+ cells and VEGF plasma levels in these patients. We also found AC133 and KDR positivity in breast carcinoma tissues. To our knowledge, this is the first report addressing the recruitment of EPC to breast tumors. Strategies to impair the mobilization and incorporation of EPC into tumors may interfere with the growth of these tumors.

In vivo Release of Vascular Endothelial Growth Factor from Colorectal Carcinomas

The formation of new blood vessels is essential for the growth of malignant tumors and their hematogenic spread. Tumor-induced neoangiogenesis occurs through sprouting of preexisting vessels. An alternative mechanism might be the recruitment of bone marrow-derived endothelial cells, or their precursors, to the tumor site by the release of vascular endothelial growth factor (VEGF) from cancer cells, i.e., tumor-induced postnatal vasculogenesis. To investigate if a significant amount of VEGF is released from malignant tumors in vivo, thus potentially mobilizing endothelial precursor cells (EPC) from the bone marrow, we measured plasma levels of soluble VEGF obtained from tumor-draining mesenteric veins (VEGF-M) during surgery and, simultaneously, in venous blood obtained distant from the tumor (VEGF-P). This analysis was performed in 29 patients with colorectal carcinoma. VEGF-M levels were substantially higher in patients with distant metastases (208 ± 61 pg/ml) compared to patients with nonmetastatic disease (99 ± 72 pg/ml, p = 0.003). Also, in patients with aggressive disease, i.e., histologically undifferentiated (G3) tumors, higher levels of VEGF-M were measured than in patients with tumors of lower histologic grading (196 ± 46 vs. 107 ± 80 pg/ml, p = 0.01). In conclusion, the release of significant amounts of soluble VEGF in vivo from clinically and/or histologically aggressive tumors might reflect their high angiogenic or vasculogenic potential, probably leading to the recruitment of EPC from the bone marrow.