Mesenchymal stem cells and their relationship to pericytes

L, da Silva Meirelles; Bc, Bellagamba; Camassola, Melissa; Nb, Nardi

doi:10.2741/4380

Cited by 37 publications

(21 citation statements)

References 155 publications

(177 reference statements)

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“…Various types of evidence suggest that pericytes behave as mesenchymal stem cells in different tissues [83], including the liver [84]. Pericytes, including HSCs, have been shown to give rise to cultured mesenchymal stromal cells (MSCs) [85][86][87], which are able to differentiate into bone, cartilage, and fat cells in vitro and secrete a number of paracrine molecules that have trophic and immunomodulatory properties [88].…”

Section: Hypothesis: Activated Hscs Resemble Mesenchymal Stromal Cellmentioning

confidence: 99%

Are Liver Pericytes Just Precursors of Myofibroblasts in Hepatic Diseases? Insights from the Crosstalk between Perivascular and Inflammatory Cells in Liver Injury and Repair

Meirelles

Marson

Solari³

et al. 2020

Cells

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Cirrhosis, a late form of liver disease, is characterized by extensive scarring due to exacerbated secretion of extracellular matrix proteins by myofibroblasts that develop during this process. These myofibroblasts arise mainly from hepatic stellate cells (HSCs), liver-specific pericytes that become activated at the onset of liver injury. Consequently, HSCs tend to be viewed mainly as myofibroblast precursors in a fibrotic process driven by inflammation. Here, the molecular interactions between liver pericytes and inflammatory cells such as macrophages and neutrophils at the first moments after injury and during the healing process are brought into focus. Data on HSCs and pericytes from other tissues indicate that these cells are able to sense pathogen- and damage-associated molecular patterns and have an important proinflammatory role in the initial stages of liver injury. On the other hand, further data suggest that as the healing process evolves, activated HSCs play a role in skewing the initial proinflammatory (M1) macrophage polarization by contributing to the emergence of alternatively activated, pro-regenerative (M2-like) macrophages. Finally, data suggesting that some HSCs activated during liver injury could behave as hepatic progenitor or stem cells will be discussed.

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Section: Hypothesis: Activated Hscs Resemble Mesenchymal Stromal Cellmentioning

confidence: 99%

Are Liver Pericytes Just Precursors of Myofibroblasts in Hepatic Diseases? Insights from the Crosstalk between Perivascular and Inflammatory Cells in Liver Injury and Repair

Meirelles

Marson

Solari³

et al. 2020

Cells

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“…PDGFRβ is a cell‐surface tyrosine‐kinase receptor that occurs as a homodimer or heterodimer (Shim et al, ). PDGFRβ and its ligands PDGF‐B and PDGF‐D play critical roles in the migration and proliferation of mesenchymal cells (Heldin et al, ; Sano et al, ), which were recently proposed to derive from pericytes under certain conditions (da Silva Meirelles et al, ). As PDGFRβ locates in pericytes and its ligand PDGF‐B is in endothelial cells, the PDGFRβ/PDGF‐B interaction could be a critical molecular pathway for pericyte–endothelial cell communication during vascularization and proper formation of the blood–brain barrier (BBB) (Gerhardt and Betsholtz, ; Hellström et al, ).…”

Section: Introductionmentioning

confidence: 99%

Dynamics of PDGFRβ expression in different cell types after brain injury

Kyyriäinen

Ndode-Ekane

Pitkänen

2016

Glia

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Platelet-derived growth factor receptor β (PDGFRβ) is upregulated after brain injury and its depletion results in the blood-brain barrier (BBB) damage. We investigated the time-window and localization of PDGFRβ expression in mice with intrahippocampal kainic acid-induced status epilepticus (SE) and in rats with lateral fluid-percussion-induced traumatic brain injury (TBI). Tissue immunohistochemistry was evaluated at several time-points after SE and TBI. The distribution of PDGFRβ was analyzed, and its cell type-specific expression was verified with double/triple-labeling of astrocytes (GFAP), NG2 cells, and endothelial cells (RECA-1). In normal mouse hippocampus, we found evenly distributed PDGFRβ+ parenchymal cells. In double-labeling, all NG2+ and 40%-60% GFAP+ cells were PDGFRβ+. After SE, PDGFRβ+ cells clustered in the ipsilateral hilus (178% of that in controls at fourth day, 225% at seventh day, P < 0.05) and in CA3 (201% at seventh day, P < 0.05), but the total number of PDGFRβ+ cells was not altered. As in controls, PDGFRβ-immunoreactivity was detected in parenchymal NG2+ and GFAP+ cells. We also observed PDGFRβ+ structural pericytes, detached reactive pericytes, and endothelial cells. After TBI, PDGFRβ+ cells clustered in the perilesional cortex and thalamus, particularly during the first post-injury week. PDGFRβ immunopositivity was observed in NG2+ and GFAP+ cells, structural pericytes, detached reactive pericytes, and endothelial cells. In some animals, PDGFRβ vascular staining was observed around the cortical glial scar for up to 3 months. Our data revealed an acute accumulation of PDGFRβ+ BBB-related cells in degenerating brain areas, which can be long lasting, suggesting an active role for PDGFRβ-signaling in blood vessel and post-injury tissue recovery. GLIA 2017;65:322-341.

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“…To study the role of perivascular cells in regulating barrier function, we used a microfluidic device in which human bone marrow stromal cells (hBMSCs), a cell population that exhibit mural cell characteristics (23)(24)(25)(26)(27)(28), lined a perfusable endothelialized channel. The device was assembled based largely on previously described models of endothelialized channels (29), in this case by casting a single, hollowed cylindrical channel (160 μm diameter) into type-I collagen within a polydimethylsiloxane (PDMS) mold containing a bulk chamber hosting the vessel and reservoir chambers for introducing media into the system.…”

Section: Bicellular Perfusable 3d Platform Recapitulates Pericyte Rolmentioning

confidence: 99%

Three-dimensional biomimetic vascular model reveals a RhoA, Rac1, and N -cadherin balance in mural cell–endothelial cell-regulated barrier function

Alimperti

Mirabella

Bajaj

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The integrity of the endothelial barrier between circulating blood and tissue is important for blood vessel function and, ultimately, for organ homeostasis. Here, we developed a vessel-on-a-chip with perfused endothelialized channels lined with human bone marrow stromal cells, which adopt a mural cell-like phenotype that recapitulates barrier function of the vasculature. In this model, barrier function is compromised upon exposure to inflammatory factors such as LPS, thrombin, and TNFα, as has been observed in vivo. Interestingly, we observed a rapid physical withdrawal of mural cells from the endothelium that was accompanied by an inhibition of endogenous Rac1 activity and increase in RhoA activity in the mural cells themselves upon inflammation. Using a system to chemically induce activity in exogenously expressed Rac1 or RhoA within minutes of stimulation, we demonstrated RhoA activation induced loss of mural cell coverage on the endothelium and reduced endothelial barrier function, and this effect was abrogated when Rac1 was simultaneously activated. We further showed that N-cadherin expression in mural cells plays a key role in barrier function, as CRISPRmediated knockout of N-cadherin in the mural cells led to loss of barrier function, and overexpression of N-cadherin in CHO cells promoted barrier function. In summary, this bicellular model demonstrates the continuous and rapid modulation of adhesive interactions between endothelial and mural cells and its impact on vascular barrier function and highlights an in vitro platform to study the biology of perivascular-endothelial interactions.

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Mesenchymal stem cells and their relationship to pericytes

Cited by 37 publications

References 155 publications

Are Liver Pericytes Just Precursors of Myofibroblasts in Hepatic Diseases? Insights from the Crosstalk between Perivascular and Inflammatory Cells in Liver Injury and Repair

Are Liver Pericytes Just Precursors of Myofibroblasts in Hepatic Diseases? Insights from the Crosstalk between Perivascular and Inflammatory Cells in Liver Injury and Repair

Dynamics of PDGFRβ expression in different cell types after brain injury

Three-dimensional biomimetic vascular model reveals a RhoA, Rac1, and N -cadherin balance in mural cell–endothelial cell-regulated barrier function

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