Isolation of tissue-resident vascular endothelial stem cells from mouse liver

Naito, Hisamichi; Wakabayashi, Taku; Ishida, Mamoru; Gil, Chang-Hyun; Iba, Tomohiro; Rahmawati, Fitriana Nur; Shimizu, Shota; Yoder, Mervin C.; Takakura, Nobuyuki

doi:10.1038/s41596-019-0276-x

Cited by 20 publications

(20 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 31 Murine vascular endothelial stem cells (CD45 − CD31 + CD157 + ) demonstrated enhanced endothelial tubule network formation, and exhibited clonal endothelial colony forming capacity vs the CD157 − population. 53 In this protocol, ECFCs were supported using an OP9 stromal cell coculture approach as previously described. 54 Although these results are akin to human ECFCs, their existence in humans has not yet been proven.…”

Section: Markers For Endothelial Progenitorsmentioning

confidence: 99%

Current Concepts on Endothelial Stem Cells Definition, Location, and Markers

Chambers

Pathak

Pedrini

et al. 2021

Stem Cells Translational Medicine

View full text Add to dashboard Cite

Ischemic vascular disease is a major cause of mortality and morbidity worldwide, and regeneration of blood vessels in perfusion-deficient tissues is a worthwhile therapeutic goal. The idea of delivering endothelial stem/progenitor cells to repair damaged vasculature, reperfuse hypoxic tissue, prevent cell death, and consequently diminish tissue inflammation and fibrosis has a strong scientific basis and clinical value. Various labs have proposed endothelial stem/progenitor cell candidates. This has created confusion, as there are profound differences between these cell definitions based on isolation methodology, characterization, and reparative biology. Here, a stricter definition based on stem cell biology principles is proposed. Although preclinical studies have often been promising, results from clinical trials have been highly contradictory and served to highlight multiple challenges associated with disappointing therapeutic benefit. This article reviews recent accomplishments in the field and discusses current difficulties when developing endothelial stem cell therapies. Emerging evidence that disputes the classic view of the bone marrow as the source for these cells and supports the vascular wall as the niche for these tissue-resident endothelial stem cells is considered. In addition, novel markers to identify endothelial stem cells, including CD157, EPCR, and CD31low VEGFR2low IL33+ Sox9+, are described.

show abstract

Section: Markers For Endothelial Progenitorsmentioning

confidence: 99%

Current Concepts on Endothelial Stem Cells Definition, Location, and Markers

Chambers

Pathak

Pedrini

et al. 2021

Stem Cells Translational Medicine

View full text Add to dashboard Cite

show abstract

“…ECs, even in a normal organ, are genetically and phenotypically heterogeneous, but more so in tumors because of the abnormal microenvironmental conditions. We have also recently reported that vascular endothelial stem cells are present in pre‐existing blood vessels, causing vigorous tumor angiogenesis 12‐14 . In addition, regarding heterogeneity, new types of ECs have been identified based on single cell RNA analysis of vascular ECs in tumors 11 .…”

Section: Discussionmentioning

confidence: 99%

“…We have explored the origin of these highly proliferative cells and determined that they are derived from vascular endothelial stem cell-like cells present in the vascular ECs of existing blood vessels. [12][13][14] For physiological angiogenesis, amelioration of ischemia or inflammation results in maturation or regression of new blood vessels.…”

Section: Con S Truc Ti On Of a Hi G Hly Hier Archi C Al B Lood Ve Smentioning

confidence: 99%

“…We have also recently reported that vascular endothelial stem cells are present in pre-existing blood vessels, causing vigorous tumor angiogenesis. [12][13][14] In addition, regarding heterogeneity, new types of ECs have been identified based on single cell RNA analysis of vascular ECs in tumors. 11 Because of the heterogeneity of blood vessels in tumors, it would be expected that tumor immunity must also be heterogeneous even within the microenvironment of the same tumor.…”

Section: Con Clus Ionsmentioning

confidence: 99%

“…The cells that are in close contact with the tip cells, just behind them, are called stalk cells, which have a marked ability to produce vascular ECs and are involved in the elongation of new blood vessels. We have explored the origin of these highly proliferative cells and determined that they are derived from vascular endothelial stem cell‐like cells present in the vascular ECs of existing blood vessels 12‐14 …”

Section: Construction Of a Highly Hierarchical Blood Vessel Architecturementioning

confidence: 99%

See 2 more Smart Citations

Vascular reconstitution in the tumor for more effective tumor immunotherapy

Takakura

2021

Cancer Science

Self Cite

View full text Add to dashboard Cite

Blood vessels play fundamental roles in homeostasis by supplying oxygen, nutrients, and immune cells to tissues on the one hand, and by removing carbon dioxide, waste products of metabolism, and excessive fluid on the other hand. Moreover, molecules secreted by endothelial cells (ECs) also have critical roles in maintaining organ integrity. Although coagulation factor VIII secretion from ECs in liver exerts its effects systemically, Wnt2 and bFGF from liver sinusoidal ECs are secreted as angiocrine factors to maintain hepatocyte survival and to regenerate the liver locally. 1 In cancer, secreted factors from tumor ECs support the growth of cancer cells and induce their stemness. 2 Therefore, aberrant overexpression of growth factors from ECs has been suggested to be one of the hallmarks of tumor malignancy.As mentioned above, blood vessels have pivotal roles for delivering immune cells to damaged or infected tissues. ECs of the venulae determine which immune cells (ie, neutrophils, T cells, or monocytes) it is appropriate to deliver to tissues in specific circumstances by regulating the respective adhesion molecules for immune cell entry and maintenance of tissue integrity. Because ECs and immune cells have the same precursors, hemogenic angioblasts (previously known as hemangioblasts) from the mesoderm, these cells control vascular formation and immunity by mutually interacting. In cancer, vascular formation is affected by hematopoietic cells, especially by regulating matrix remodeling, growth of ECs,

show abstract

Aging impairs the ability of vascular endothelial stem cells to generate endothelial cells in mice

Shimizu,

Iba,

Naito

et al. 2023

Angiogenesis

Self Cite

View full text Add to dashboard Cite

Tissue-resident vascular endothelial stem cells (VESCs), marked by expression of CD157, possess long-term repopulating potential and contribute to vascular regeneration and homeostasis in mice. Stem cell exhaustion is regarded as one of the hallmarks of aging and is being extensively studied in several types of tissue-resident stem cells; however, how aging affects VESCs has not been clarified yet. In the present study, we isolated VESCs from young and aged mice to compare their potential to differentiate into endothelial cells in vitro and in vivo. Here, we report that the number of liver endothelial cells (ECs) including VESCs was lower in aged (27–28 month-old) than young (2–3 month-old) mice. In vitro culture of primary VESCs revealed that the potential to generate ECs is impaired in aged VESCs isolated from liver and lung relative to young VESCs. Orthotopic transplantation of VESCs showed that aged VESCs and their progeny expand less efficiently than their young counterparts when transplanted into aged mice, but they are equally functional in young recipients. Gene expression analysis indicated that inflammatory signaling was more activated in aged ECs including VESCs. Using single-cell RNA sequencing data from the Tabula Muris Consortium, we show that T cells and monocyte/macrophage lineage cells including Kupffer cells are enriched in the aged liver. These immune cells produce IL-1β and several chemokines, suggesting the possible involvement of age-associated inflammation in the functional decline of VESCs with age.

show abstract

Isolation of tissue-resident vascular endothelial stem cells from mouse liver

Cited by 20 publications

References 38 publications

Current Concepts on Endothelial Stem Cells Definition, Location, and Markers

Current Concepts on Endothelial Stem Cells Definition, Location, and Markers

Vascular reconstitution in the tumor for more effective tumor immunotherapy

Aging impairs the ability of vascular endothelial stem cells to generate endothelial cells in mice

Contact Info

Product

Resources

About