Fluorescent pegylated nanoparticles demonstrate fluid-phase pinocytosis by macrophages in mouse atherosclerotic lesions

Buono, Chiara; Anzinger, Joshua J.; Amar, Marcelo; Kruth, Howard S.

doi:10.1172/jci35548

Cited by 88 publications

(60 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…+ macrophages in atherosclerotic legions (29). The mechanism through which QDs delivered at one local injury became associated with macrophages in a separate local injury site remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Human stem cell delivery for treatment of large segmental bone defects

Dupont

Sharma²,

Stevens³

et al. 2010

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

170

145

View full text Add to dashboard Cite

Local or systemic stem cell delivery has the potential to promote repair of a variety of damaged or degenerated tissues. Although various stem cell sources have been investigated for bone repair, few comparative reports exist, and cellular distribution and viability postimplantation remain key issues. In this study, we quantified the ability of tissue-engineered constructs containing either human fetal or adult stem cells to enhance functional repair of nude rat critically sized femoral defects. After 12 weeks, defects treated with cell-seeded polymer scaffolds had significantly higher bone ingrowth and torsional strength compared to those receiving acellular scaffolds, although there were no significant differences between the cell sources. Next, stem cells were labeled with fluorescent quantum dots (QDs) in an attempt to noninvasively track their distribution after delivery on scaffolds. Clear fluorescence was observed at implantation sites throughout the study; however, beginning 7-10 days after surgery, signals were also observed at contralateral sites treated with acellular QD-free scaffolds. Although immunostaining for human nuclei revealed retention of some cells at the implantation site, no human cells were detected in the control limb defects. Additional histological analysis of implantation and control defect tissues revealed macrophages containing endocytosed QDs. Furthermore, QD-labeling appeared to diminish transplanted cell function resulting in reduced healing responses. In summary, augmentation of polymeric scaffolds with stem cells derived from fetal and adult tissues significantly enhanced healing of large segmental bone defects; however, QD labeling of stem cells eliminated the observed therapeutic effect and failed to conclusively track stem cell location long-term in vivo.bone tissue engineering | cell tracking | in vivo | quantum dots | stem cells

show abstract

Section: Discussionmentioning

confidence: 99%

Human stem cell delivery for treatment of large segmental bone defects

Dupont

Sharma²,

Stevens³

et al. 2010

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

170

145

View full text Add to dashboard Cite

show abstract

“…Cholesterol mass and isotope fl ux studies were conducted on J774 (murine cell line) cells and mouse peritoneal macrophage (MPM) cells that contained both normal and elevated levels of cholesterol. The level of cell cholesterol infl uences fl ux in a number of ways, including modulating the expression level of cell proteins mediating effl ux such as ABCA1, ABCG1, and SR-BI, and proteins, such as LDL and scavenger receptors, which participate in lipoprotein uptake ( 7,10 ) or infl ux. The fractional effl ux values were determined using cells prelabeled with [ 3 H]cholesterol and net fl ux was measured directly by quantitating changes in cell cholesterol mass upon incubation with either human sera or apolipoprotein (apo)-B-depleted sera.…”

Section: Discussionmentioning

confidence: 99%

Importance of macrophage cholesterol content on the flux of cholesterol mass

Sankaranarayanan

Llera-Moya

Drazul-Schrader

et al. 2010

Journal of Lipid Research

View full text Add to dashboard Cite

When cells in culture are incubated with serum, there is a fl ux of free cholesterol (FC) out of the cell (effl ux) while simultaneously there is movement of lipoprotein-derived FC and esterifi ed cholesterol (CE) into the cell (infl ux). The difference between infl ux and effl ux is the net change in cell cholesterol content, or net fl ux. Net fl ux may result in net accumulation, net depletion, or no change in cell cholesterol content if infl ux and effl ux are equal. The net fl ux of cholesterol plays a major role in maintaining cell cholesterol homeostasis, and this is particularly important for macrophages in the vessel wall where net infl ux results in the deposition of excess cholesterol and formation of macrophage-derived foam cells ( 1 ). Many investigations have quantitated cholesterol effl ux using a variety of cell types and extracellular acceptors, which is relatively simple because only FC is released from cells. These studies have identifi ed a number of pathways that mediate effl ux ( 2 ) including 1 ) aqueous diffusion ( 3 ), 2 ) ATP binding cassette transporter A1 (ABCA1) ( 4 ), 3 ) ATP binding cassette transporter G1 (ABCG1) ( 5 ), and 4 ) scavenger receptor class B type I (SR-BI) ( 6 ). The infl ux of cholesterol from exogenous lipoproteins is much more diffi cult to quantitate because both FC and CE are incorporated by aqueous diffusion, SR-BI, classical LDL receptors, scavenger receptors, and pinocytosis ( 7 ).Bidirectional cholesterol fl ux is infl uenced by the array of lipoproteins in serum, the combination of effl ux pathways available to the cells, and the cholesterol status of the cells ( 8,9 ). In the present study we have incubated cells with a number of different normolipemic human sera and quantitated the infl uence of each serum sample on fractional cholesterol effl ux as well as on the net fl ux of cho- Abstract

show abstract

“…The detection of in vivo pinocytotic activity was performed as described previously (8). Capn6 +/y Ldlr…”

Section: Methodsmentioning

confidence: 99%

“…The pinocytotic uptake of native LDL is also independent of the degree of LDL oxidation and does not saturate, which is distinct from the properties of receptor-mediated uptake of modified LDL. Buono et al reported that pinocytotic activity is potentiated in macrophages in murine atherosclerotic lesions (8). Although pinocytosis is mediated through Rho GTPase cytoskeletal dynamics (9,10), little is known about its regulatory mechanisms.…”

Section: Introductionmentioning

confidence: 99%