Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

Li, Hongzhe; Ghazanfari, Roshanak; Zacharaki, Dimitra; Ditzel, Nicholas; Isern, Joan; Ekblom, Marja; Méndez-Ferrer, Simón; Kassem, Moustapha; Scheding, Stefan

doi:10.1016/j.stemcr.2014.09.018

Cited by 94 publications

(106 citation statements)

References 17 publications

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“…2B). Together, these results show that the Lin -EpCAM -CD73 + CD90 + cells isolated from human lungs match the criteria of pericytes, as demonstrated by morphology, the cell surface markers NG2 4 and PDGFRa 18,19 and response to TGF-b1. These cells are thus a suitable choice as perivascular supporting cells for an in vitro lung microvascular model.…”

Section: Primary Human Lung Pericyte Isolation and Characterizationsupporting

confidence: 63%

Primary Human Lung Pericytes Support and Stabilize In Vitro Perfusable Microvessels

Bichsel

Hall

Schmid

et al. 2015

Tissue Engineering Part A

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The formation of blood vessels is a complex tissue-specific process that plays a pivotal role during developmental processes, in wound healing, cancer progression, fibrosis, and other pathologies. To study vasculogenesis and vascular remodeling in the context of the lung, we developed an in vitro microvascular model that closely mimics the human lung microvasculature in terms of three-dimensional architecture, accessibility, functionality, and cell types. Human pericytes from the distal airway were isolated and characterized using flow cytometry. To assess their role in the generation of normal microvessels, lung pericytes were mixed in fibrin gel and seeded into well-defined microcompartments together with primary endothelial cells (human umbilical cord vein endothelial cells). Patent microvessels covering an area of 3.1 mm(2) formed within 3-5 days and were stable for up to 14 days. Soluble signals from the lung pericytes were necessary to establish perfusability, and pericytes migrated toward endothelial microvessels. Cell-cell communication in the form of adherens and tight junctions, as well as secretion of basement membrane were confirmed using transmission electron microscopy and immunocytochemistry on chip. Direct coculture of pericytes with endothelial cells decreased the microvascular permeability by one order of magnitude from 17.8×10(-6) to 2.0×10(-6) cm/s and led to vessels with significantly smaller and less variable diameter. Upon phenylephrine administration, vasoconstriction was observed in microvessels lined with pericytes, but not in endothelial microvessels only. Perfusable microvessels were also generated with human lung microvascular endothelial cells and lung pericytes. Human lung pericytes were thus shown to have a prominent influence on microvascular morphology, permeability, vasoconstriction, and long-term stability in an in vitro microvascular system. This biomimetic platform opens new possibilities to test functions and interactions of patient-derived cells in a physiologically relevant microvascular setting.

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Section: Primary Human Lung Pericyte Isolation and Characterizationsupporting

confidence: 63%

Primary Human Lung Pericytes Support and Stabilize In Vitro Perfusable Microvessels

Bichsel

Hall

Schmid

et al. 2015

Tissue Engineering Part A

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“…One limitation of our study is that by using PDGFRα positively selected mammary fibroblasts, we may be evaluating a subset of mammary fibroblasts, as other PDGFRα -fibroblasts have been reported, such as in bone marrow (76). Further, while we confirmed these PDGFRα + cells to be largely devoid of epithelial, immune, and endothelial cell type markers, this population likely includes pericytes and perivascular fibroblasts (77,78).…”

Section: Ly6gmentioning

confidence: 65%

Physiologically activated mammary fibroblasts promote postpartum mammary cancer

Guo¹,

Minnier²,

Burchard³

et al. 2017

JCI Insight

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“…Cell cycle analysis furthermore revealed that the majority of 44 the CD140a low/− cells were in the G 0 phase of the cell cycle. Cultured stromal cells derived from sorted CD140a low/− cells showed a typical MSC surface marker profile and demonstrated robust multilineage differentiation potential both in vitro and, importantly, in vivo in xenotransplantation experiments using immunodeficient NSG mice.…”

Section: But Not In the Cd271mentioning

confidence: 99%

“…44 The aim of this comparison was to identify potential novel MSC surface markers that could be used to improve current MSC isolation approaches.…”

Section: But Not In the Cd271mentioning

confidence: 99%

“…CFU-F frequencies were additionally confirmed in single-cell and limiting-dilution assays. 44 Recently, Zhou et al 45 reported that leptin receptor (LepR) was a marker that highly enriched BM CFU-Fs in mice, and that approximately 94% of BM CFU-Fs were LepR + . Interestingly, the LepR gene was also one of the genes found to be upregulated in human CD271…”

Section: But Not In the Cd271mentioning

confidence: 99%

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Isolation and characterization of primary bone marrow mesenchymal stromal cells

Ghazanfari

Zacharaki

et al. 2016

Annals of the New York Academy of Sciences

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138

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Bone marrow (BM) contains a rare population of mesenchymal stromal cells (MSCs), which have been characterized as nonhematopoietic skeletal progenitor cells with central importance for the hematopoietic microenvironment. Classically, MSCs are isolated by plastic adherence and subsequent culture. However, as cultured stromal cells differ from their in vivo progenitors, it is important to identify the phenotype of the primary MSCs to study these cells in more detail. In the past years, several surface markers have been reported to be suitable for effective enrichment of BM-MSCs, and recent data indicate that the putative MSC stem/progenitor cell population in human adult BM is highly enriched in Lin − CD45 − CD271 + CD140a (PDGFR␣) low/− cells. Moreover, surface marker combinations have been described for the isolation of MSCs from murine BM. On the basis of these findings, the role of primary MSCs can now be studied in normal and, importantly, diseased BM. Furthermore, genetically engineered mouse models have been developed as powerful tools to investigate well-defined BM stromal cell populations in vivo. Our discussion aims to provide a concise overview of the current state of the art in BM-MSC isolation in humans and briefly present murine MSC isolation approaches and genetic models.

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Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

Cited by 94 publications

References 17 publications

Primary Human Lung Pericytes Support and Stabilize In Vitro Perfusable Microvessels

Primary Human Lung Pericytes Support and Stabilize In Vitro Perfusable Microvessels

Physiologically activated mammary fibroblasts promote postpartum mammary cancer

Isolation and characterization of primary bone marrow mesenchymal stromal cells

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