/ Pezzella, Francesco; Gatter, Kevin; Qian, Chao Nan

We tested the hypothesis that Ang II impairs endothelial differentiation and vasculogenic ..

In: Chinese Journal of Cancer, Vol

OBJECTIVE-Vascular progenitors of bone marrow origin participate to neovascularization at sites of wound healing and transplantation. We hypothesized that the biological purpose of this bone marrow-derived vascular component is to contribute angiogenic and survival functions distinct from those provided by the local tissue-derived vasculature. RESEARCH DESIGN AND METHODS AND RESULTS-To address this hypothesis, we investigated the functional impact of bone marrow-derived vascular cells on pancreatic islets engraftment using bone marrow-reconstituted Id1 +/-Id3 -/- mice, a model of bone marrow-derived vasculogenesis. We show that, in this model, bone marrow-derived vasculogenic cells primarily contribute to the formation of new blood vessels within islet transplants. In contrast, graft revascularization in a wild-type background occurs by tissue-derived blood vessels only. Using these distinct transplant models in which bone marrow- and tissue-derived vasculature are virtually mutually exclusive, we demonstrate that bone marrow-derived vasculogenic cells exhibit enhanced angiogenic functions and support prompt activation of islets survival pathways, which significantly impact on islets engraftment and function. Moreover, gene profiling of vascular and inflammatory cells of the grafts demonstrate that neovascularization by bone marrow-derived cells is accompanied by the activation of a genetic program uniquely tuned to downregulate harmful inflammatory responses and to promote tissue repair. CONCLUSIONS-These studies uncover the biological significance of bone marrow-derived vasculogenic cells in the response to injury during transplantation. Enhancing the contribution of bone marrow-derived vasculogenic cells to transplantation sites may help to overcome both limited angiogenic responses of the adult tissue-derived vasculature and untoward effects of inflammation on transplant engraftment.

Nonspecific Capillary Proliferation and Vasculopathy Indicate ..

Nonspecific Capillary Proliferation and Vasculopathy Indicate Skin ..

N2 - OBJECTIVE-Vascular progenitors of bone marrow origin participate to neovascularization at sites of wound healing and transplantation. We hypothesized that the biological purpose of this bone marrow-derived vascular component is to contribute angiogenic and survival functions distinct from those provided by the local tissue-derived vasculature. RESEARCH DESIGN AND METHODS AND RESULTS-To address this hypothesis, we investigated the functional impact of bone marrow-derived vascular cells on pancreatic islets engraftment using bone marrow-reconstituted Id1 +/-Id3 -/- mice, a model of bone marrow-derived vasculogenesis. We show that, in this model, bone marrow-derived vasculogenic cells primarily contribute to the formation of new blood vessels within islet transplants. In contrast, graft revascularization in a wild-type background occurs by tissue-derived blood vessels only. Using these distinct transplant models in which bone marrow- and tissue-derived vasculature are virtually mutually exclusive, we demonstrate that bone marrow-derived vasculogenic cells exhibit enhanced angiogenic functions and support prompt activation of islets survival pathways, which significantly impact on islets engraftment and function. Moreover, gene profiling of vascular and inflammatory cells of the grafts demonstrate that neovascularization by bone marrow-derived cells is accompanied by the activation of a genetic program uniquely tuned to downregulate harmful inflammatory responses and to promote tissue repair. CONCLUSIONS-These studies uncover the biological significance of bone marrow-derived vasculogenic cells in the response to injury during transplantation. Enhancing the contribution of bone marrow-derived vasculogenic cells to transplantation sites may help to overcome both limited angiogenic responses of the adult tissue-derived vasculature and untoward effects of inflammation on transplant engraftment.

Vasculogenic Erectile Dysfunction Is a Predictor of Abnormal Stress Echocardiography

To confirm the hypothesis that aggressive tumor cells can increase the vasculogenic ability of MSCs, a standard B16/F10 mouse melanoma test system was used.

the “artery size” hypothesis ..


vessel co-option and vasculogenic mimicry.

Vasculogenesis is a process of blood vessel formation through de novo production of endothelial cells, originally observed during the embryonic development. Tumor vasculogenesis denotes that some cancer cells can spontaneously form blood vessels in tumor via transdifferentiation into endothelial-like cells. A cancer resembles a neo-organ, composed of various stages of developing cancer cells, including precancerous stem cells (pCSCs) –, cancer stem cells (CSCs) – and cancer cells . A cancer cell is supposed to be developed from a process of tumor-initiating cells (TICs)→pCSCs→CSCs→cancer cells . CSCs have been shown to promote tumor angiogenesis through secreting growth factor VEGF , although their potential for transdifferentiation into endothelial cells has not been demonstrated. Recently, we have discovered that the precancerous stem cells (pCSCs), representing the premalignant stage of developing CSCs, have the potential for both benign and malignant differentiation , . The pCSCs can develop into tumors in severe combined immunodeficiency disease (SCID) mice, but not in bone marrow (BM)-reconstituted (BMR) mice, blastocyst chimera mice, and immunocompetent (IC) mice . In the BMR mice, however, pCSCs can differentiate into various types of tissue cells, including endothelial-like cells, suggesting that they might have the capacity to form blood vessels in tumorigenic environments . To verify the hypothesis, we have investigated the tumor vasculogenic capacity of pCSCs in a murine model of lymphoma , . In the pCSC-derived tumor, tumor blood vessels were essentially derived from transplanted pCSCs. The pCSCs are much more potent in tumor neo-vascularization compared to the differentiated tumor monocytic cells (TMCs) derived from the same tumor. Various types of human cancer cell lines that should contain pCSCs and CSCs also exhibited the potential for tumor vasculogenesis in tumor xenografts. Tumor vascular endothelial cells were inevitably defective in phenotype and function with remarkable variations between individuals. Consistently, most endothelial cells were abnormal in human tumor vasculature. Thus, pCSCs can serve as tumor vasculogenic stem/progenitor cells. The finding may explain why anti-angiogenic cancer therapy trails are facing serious challenge .

Vasculogenic erectile dysfunction is an early manifestation ..

AB - OBJECTIVE-Vascular progenitors of bone marrow origin participate to neovascularization at sites of wound healing and transplantation. We hypothesized that the biological purpose of this bone marrow-derived vascular component is to contribute angiogenic and survival functions distinct from those provided by the local tissue-derived vasculature. RESEARCH DESIGN AND METHODS AND RESULTS-To address this hypothesis, we investigated the functional impact of bone marrow-derived vascular cells on pancreatic islets engraftment using bone marrow-reconstituted Id1 +/-Id3 -/- mice, a model of bone marrow-derived vasculogenesis. We show that, in this model, bone marrow-derived vasculogenic cells primarily contribute to the formation of new blood vessels within islet transplants. In contrast, graft revascularization in a wild-type background occurs by tissue-derived blood vessels only. Using these distinct transplant models in which bone marrow- and tissue-derived vasculature are virtually mutually exclusive, we demonstrate that bone marrow-derived vasculogenic cells exhibit enhanced angiogenic functions and support prompt activation of islets survival pathways, which significantly impact on islets engraftment and function. Moreover, gene profiling of vascular and inflammatory cells of the grafts demonstrate that neovascularization by bone marrow-derived cells is accompanied by the activation of a genetic program uniquely tuned to downregulate harmful inflammatory responses and to promote tissue repair. CONCLUSIONS-These studies uncover the biological significance of bone marrow-derived vasculogenic cells in the response to injury during transplantation. Enhancing the contribution of bone marrow-derived vasculogenic cells to transplantation sites may help to overcome both limited angiogenic responses of the adult tissue-derived vasculature and untoward effects of inflammation on transplant engraftment.