Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells

Rajantie, Iiro; Ilmonen, Maritta; Alminaite, A.; Özerdem, Uğur; Alitalo, Kari; Salvén, Petri

doi:10.1182/blood-2004-01-0336

Cited by 368 publications

(261 citation statements)

References 27 publications

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“…The involvement of BM-MLCs in physiological revascularization is in agreement with earlier studies that BM-derived cells contribute to the growth of blood vessels during postnatal vascular regeneration and vascular remodeling after injury. 24,25 In the CNS, BM-MLCs and activated microglias can be seen at the border of cerebral infarcted areas in the ischemic brain, 26 as we observed at the border between vascular and avascular retina (Figure 4a). The cells in the cerebral ischemic areas may secrete a variety of proinflammatory cytokines, 27 neurotrophic factors, and angiogenic factors such as VEGF.…”

Section: Discussionmentioning

confidence: 70%

Bone marrow-derived monocyte lineage cells recruited by MIP-1β promote physiological revascularization in mouse model of oxygen-induced retinopathy

Ishikawa

Nakao

Sassa

et al. 2012

Laboratory Investigation

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Recent clinical observations have indicated that vascular endothelial growth factor (VEGF) is a key factor that stimulates the development of preretinal pathological neovascularization (NV). However, it has not been established how intraretinal physiological revascularization of hypoxic avascular areas is regulated. Our earlier study on the gene expression profile of hypoxic retinas in a mouse model of oxygen-induced retinopathy (OIR) showed that macrophage inflammatory protein-1b (MIP-1b) was the most upregulated protein. The purpose of this study was to investigate the role played by MIP-1b in recruiting bone marrow-derived monocyte lineage cells (BM-MLCs) in a mouse model of OIR. Our results showed that MIP-1b was upregulated, and its receptor, CCR5, was expressed in BM-MLCs in the hypoxic inner retina. Neutralizing Ab against MIP-1b reduced the infiltration of BM-MLCs into the OIR retinas and increased the avascular area and preretinal neovascular tufts. A very strong significant correlation was found between the area of the preretinal neovascular tufts and the avascular area, regardless of the extent of BM-MLC infiltration into the OIR retinas. Additional treatment with VEGF-A-neutralizing Ab showed that the MIP-1b-regulated pathological NV strongly depended on VEGF-A, which was probably secreted by the hypoxic avascular retinas. These results indicate that MIP-1b is involved in the recruitment of BM-MLCs, which have a significant role in the physiological revascularization of hypoxic avascular retinas. Overall, these findings indicate that the MIP-1b induction of BM-MLCs might possibly be used to promote intraretinal revascularization and thus prevent the abnormal NV in ischemic vision-threatening retinal diseases. Tissue hypoxia is believed to be the common mechanism that initiates a series of events leading to compensatory angiogenesis. Hypoxia-induced retinal neovascularization (NV) is the main contributor to proliferative vascular diseases, such as diabetic retinopathy, retinopathy of prematurity, and retinal vein occlusion. These diseases can lead to irreversible damage to visual function.To determine the factors that are activated during retinal hypoxia, we performed a gene expression profile of hypoxic retinas obtained from a mouse model of oxygen-induced retinopathy (OIR) using gene microarray analyses. The results identified the functional set of genes that are related to the post-ischemic inflammation, neural and vascular development, and subsequent pathological NV. The most upregulated gene among the differentially expressed genes in hypoxic retinas was the macrophage inflammatory protein1b (MIP-1b) and not vascular endothelial growth factor A (VEGF-A) and other chemokines. 1 MIP-1b, also known as chemokine CC motif ligand 4, is a member of the CC chemokine family that are characterized by their ability to direct migration of leukocytes into inflamed tissues. 2 MIP-1b was first isolated from the culture medium of LPS-activated macrophages, 3 and it recruited macrophages/microglia to the sites of...

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Section: Discussionmentioning

confidence: 70%

Bone marrow-derived monocyte lineage cells recruited by MIP-1β promote physiological revascularization in mouse model of oxygen-induced retinopathy

Ishikawa

Nakao

Sassa

et al. 2012

Laboratory Investigation

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“…These observations further established the identity of X-gal-positive cells as pericytes, and confirmed that a small fraction of this cell type is generated by cell fusion under normal conditions. Several groups have recently shown the contribution of BMDC and hematopoietic stem cells to the formation of pericytes after stroke (Kokovay et al, 2006;Rajantie et al, 2004). To study the implication of cell fusion during poststroke angiogenesis, a cerebral ischemia/hypoxia episode was induced in 2 months old BMDC chimeric mice.…”

Section: Resultsmentioning

confidence: 99%

Cell Fusion Contributes to Pericyte Formation after Stroke

Piquer-Gil

García‐Verdugo

Zipančić

et al. 2008

J Cereb Blood Flow Metab

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Recent reports have shown that bone marrow-derived cells (BMDCs) contribute to the formation of vasculature after stroke. However, the mechanism by which mural cells are formed from BMDC remains elusive. Here, we provide direct evidence that the cell fusion process contributes to the formation of pericytes after stroke. We generated mouse bone marrow chimeras using a cre/lox system that allows the detection of fusion events by X-gal staining. In these mice, we detected X-gal-positive cells that expressed vimentin and desmin, specific markers of mature murine pericytes. Electron microscopy confirmed that fused cells possessed basal lamina and characteristics of pericytes. Furthermore, induction of stroke increased significantly the presence of fused cells in the ischemic area. These cells expressed markers of developing pericytes such as NG2. We conclude that cell fusion participates actively in the generation of vascular tissue through pericyte formation under normal as well as pathologic conditions.

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“…For instance studies have identified bone marrow-derived PDGFR-β + /Sca-1 + /CD11b + pericyte progenitors [102], bone marrow-derived CD45 + /CD11b + progenitors [103], and Sca-1 + /Tie2 + /CD13 + pericyte progenitors that have been associated with tumour development [104]. To our knowledge, there is no information on the osteochondrogenic capacity of these cells and as such their potential roles during HO remains unknown.…”

Section: Pericyte Progenitor Cellsmentioning

confidence: 99%