Identification and characterization of a resident vascular stem/progenitor cell population in preexisting blood vessels

Naito, Hisamichi; Kidoya, Hiroyasu; Sakimoto, Susumu; Wakabayashi, Taku; Takakura, Nobuyuki

doi:10.1038/emboj.2011.465

Cited by 154 publications

(159 citation statements)

References 53 publications

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“…In a dog stenotic artery model, these cells were shown to be capable in vivo of coronary artery regeneration (4). These findings were confirmed through studies carried out in normal mice, providing evidence about the existence of a side population of CD31 + CD45 − endothelial cells present in the inner surface of blood vessels and able to induce in vivo the reconstitution of durable, functioning blood vessels in ischemic milieu (5,6). A large number of studies carried out in these last years was focused to identify and to characterize cells endowed with a potential endothelial progenitor cell activity present at the level of hematopoietic tissues or circulating in the blood.…”

supporting

confidence: 69%

Endothelial progenitor cells in hematologic malignancies

Testa

Saulle

Castelli

et al. 2016

Stem Cell Investig.

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supporting

confidence: 69%

Endothelial progenitor cells in hematologic malignancies

Testa

Saulle

Castelli

et al. 2016

Stem Cell Investig.

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“…However, their characteristics and contribution to the tumor vasculature have not been clearly defined. In earlier work, we identified stem/ progenitor-like ECs in peripheral blood vessels based on their ability to efflux Hoechst 33342 dye (14). Cells that do this are termed side population (SP) cells because of their characteristic appearance in flow cytometry.…”

Section: Introductionmentioning

confidence: 99%

Endothelial Side Population Cells Contribute to Tumor Angiogenesis and Antiangiogenic Drug Resistance

et al. 2016

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Angiogenesis plays a crucial role in tumor growth, with an undisputed contribution of resident endothelial cells (EC) to new blood vessels in the tumor. Here, we report the definition of a small population of vascular-resident stem/progenitor-like EC that contributes predominantly to new blood vessel formation in the tumor. Although the surface markers of this population are similar to other ECs, those from the lung vasculature possess colony-forming ability in vitro and contribute to angiogenesis in vivo. These specific ECs actively proliferate in lung tumors, and the percentage of this population significantly increases in the tumor vasculature relative to normal lung tissue. Using genetic recombination and bone marrow transplant models, we show that these cells are phenotypically true ECs and do not originate from hematopoietic cells. After treatment of tumors with antiangiogenic drugs, these specific ECs selectively survived and remained in the tumor. Together, our results established that ECs in the peripheral vasculature are heterogeneous and that stem/progenitor-like ECs play an indispensable role in tumor angiogenesis as EC-supplying cells. The lack of susceptibility of these ECs to antiangiogenic drugs may account for resistance of the tumor to this drug type. Thus, inhibiting these ECs might provide a promising strategy to overcome antiangiogenic drug resistance.

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“…To our knowledge, 8,19,39 these vascular resident stem cells can differentiate into either ECs or PCs to promote angiogenesis in vivo, but cannot acquire both kinds of cells to form capillary-like structures. Early studies demonstrated that MSCs formed capillary-like structures, composed of an endothelial tube covered by PCs.…”

Section: Mpcs Are Capillary-forming Stem Cellsmentioning

confidence: 99%

“…3,33 Recently, vascular resident endothelial progenitor cells (EPCs) were identified by means of a Hoechst-labeled side population. 39 Vascular resident EPCs differentiate into ECs, and restore blood flow and reconstitute long-term surviving blood vessels.…”

Section: Mpcs Are Capillary-forming Stem Cellsmentioning

confidence: 99%

Immortalized multipotent pericytes derived from the vasa vasorum in the injured vasculature. A cellular tool for studies of vascular remodeling and regeneration

Kabara

Kawabe

Matsuki

et al. 2014

Laboratory Investigation

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Adventitial microvessels, vasa vasorum in the vessel walls, have an active role in the vascular remodeling, although its mechanisms are still unclear. It has been reported that microvascular pericytes (PCs) possess mesenchymal plasticity. Therefore, microvessels would serve as a systemic reservoir of stem cells and contribute to the tissues remodeling. However, most aspects of the biology of multipotent PCs (mPCs), in particular of pathological microvessels are still obscure because of the lack of appropriate methods to detect and isolate these cells. In order to examine the characteristics of mPCs, we established immortalized cells residing in adventitial capillary growing at the injured vascular walls. We recently developed in vivo angiogenesis to observe adventitial microvessels using collagen-coated tube (CCT), which also can be used as an adventitial microvessel-rich tissue. By using the CCT, CD146-or NG2-positive cells were isolated from the adventitial microvessels in the injured arteries of mice harboring a temperature-sensitive SV40 T-antigen gene. Several capillary-derived endothelial cells (cECs) and PCs (cPCs) cell lines were established. cECs and cPCs maintain a number of key endothelial and PC features. Co-incubation of cPCs with cECs formed capillary-like structure in Matrigel. Three out of six cPC lines, termed capillary mPCs demonstrated both mesenchymal stem cell-and neuronal stem cell-like phenotypes, differentiating effectively into adipocytes, osteoblasts, as well as schwann cells. mPCs differentiated to ECs and PCs, and formed capillary-like structure on their own. Transplanted DsRed-expressing mPCs were resident in the capillary and muscle fibers and promoted angiogenesis and myogenesis in damaged skeletal muscle. Adventitial mPCs possess transdifferentiation potential with unique phenotypes, including the reconstitution of capillary-like structures. Their phenotype would contribute to the pathological angiogenesis associated with vascular remodeling. These cell lines also provide a reproducible cellular tool for high-throughput studies on angiogenesis, vascular remodeling, and regeneration as well.

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Identification and characterization of a resident vascular stem/progenitor cell population in preexisting blood vessels

Cited by 154 publications

References 53 publications

Endothelial progenitor cells in hematologic malignancies

Endothelial progenitor cells in hematologic malignancies

Endothelial Side Population Cells Contribute to Tumor Angiogenesis and Antiangiogenic Drug Resistance

Immortalized multipotent pericytes derived from the vasa vasorum in the injured vasculature. A cellular tool for studies of vascular remodeling and regeneration

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