This Article Abstract Full Text (PDF) All Versions of this Article: 106/10/1199    most recent 01.CIR.0000031525.61826.A8v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Simper, D. Articles by Caplice, N. M. Search for Related Content PubMed PubMed Citation Articles by Simper, D. Articles by Caplice, N. M. Pubmed/NCBI databases Medline Plus Health Information Stem Cells Related Collections Pathophysiology Smooth muscle proliferation and differentiation Mechanism of atherosclerosis/growth factors Other Vascular biology

(Circulation. 2002;106:1199.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Smooth Muscle Progenitor Cells in Human Blood

David Simper, MD; Paul G. Stalboerger, BS; Carmelo J. Panetta, MD; Shaohua Wang, MD; Noel M. Caplice, MD, PhD

From the Division of Cardiovascular Diseases and Molecular Medicine Program, Mayo Clinic, Rochester, Minn.

Correspondence to Noel M. Caplice, MD, PhD, Division of Cardiovascular Diseases and Molecular Medicine Program, Mayo Clinic, Rochester, MN 55905. E-mail caplice.noel{at}mayo.edu

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background— Recent animal data suggest that vascular smooth muscle cells within the neointima of the vessel wall may originate from bone marrow, providing indirect evidence for circulating smooth muscle progenitor cells (SPCs). Evidence for circulating SPCs in human subjects does not exist, and the mechanism whereby such putative SPCs may home to sites of plaque formation is presently not understood but is likely to involve expression of specific surface adhesion molecules, such as integrins. In this study, we aimed to culture smooth muscle outgrowth cells (SOCs) from SPCs in human peripheral blood and characterize surface integrin expression on these cells.

Methods and Results— Human mononuclear cells isolated from buffy coat were seeded on collagen type 1 matrix and outgrowth cells selected in endothelial growth medium (EGM-2) or EGM-2 and platelet-derived growth factor BB. Selection in platelet-derived growth factor BB–enriched medium caused rapid outgrowth and expansion of SOC to >40 population doublings in a 4-month period. These SOCs were positive for smooth muscle cell–specific actin (SMA), myosin heavy chain, and calponin on immunofluorescence and Western blotting and were also positive for CD34, Flt1, and Flk1 receptor but negative for Tie-2 receptor expression, suggesting a potential bone marrow angioblastic origin. In contrast, endothelial outgrowth cells (EOCs) grown in EGM-2 alone and the initial MNC population were negative for these smooth muscle–specific markers. Integrin ₅ß₁ expression by FACS and Western blotting was significantly increased in SOCs compared with EOCs, and this was confirmed by 8-fold greater adhesion of SOC to fibronectin (P<0.001), an effect that could be decreased using an ₅ß₁ antibody. Finally, SOC showed a significantly greater in vitro proliferative potential compared with EOCs of similar passage (P<0.001).

Conclusions— This study demonstrates for the first time outgrowth of smooth muscle cells with a specific growth, adhesion, and integrin profile from putative SPC in human blood. These data have implications for our understanding of adult vascular smooth muscle cell differentiation, proliferation, and homing. (Circulation. 2002;106:1199–1204.)

Key Words: muscle, smooth • progenitor • blood cells

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Vascular smooth muscle cell migration, proliferation, and matrix synthesis within the intima of medium-sized and large vessels is thought to play a major role in atherosclerosis development in adult human subjects.¹ In the embryo, these vascular cells have a complex origin, with the first smooth muscle cells surrounding endothelial tubes being derived from transdifferentiated endothelium during nascent vascular and cardiac valve development. ² Several growth factors have been implicated in embryonic smooth muscle cell differentiation, including transforming growth factors ß₁, ß₃, and platelet-derived growth factor BB (PDGF-BB).^2–4

Recently, Yamashita et al⁵ reported embryonic vascular progenitors capable of differentiating into both endothelial and smooth muscle–like cells in response to vascular endothelial growth factor (VEGF) and PDGF-BB selection, respectively. Presently, there is no evidence for such growth factor–driven differentiation events in adult human subjects. However, there is accumulating evidence from animal studies that smooth muscle cells contributing to vascular disease may originate from bone marrow–derived progenitor cells, with subsequent homing of these cells to experimental atherosclerotic plaque.^6–9 These data, in addition to established evidence for circulating adult endothelial progenitor cells (EPCs),^6,10,11 suggest the possibility that a distinct smooth muscle progenitor cell (SPC) may also be present in human blood.

Understanding the phenotype of any circulating SPC may have implications for development of novel therapies to modulate homing of these cells to the vessel wall. Intrinsic to this latter understanding may be the identification of specific surface adhesion molecules, such as integrins, which are known to be important in homing of blood-borne progenitor cells to specific sites in vivo.¹²

In the present study, we tested the hypothesis that outgrowth from human peripheral blood MNC in PDGF BB–enriched medium would result in SPC differentiation into smooth muscle outgrowth cells (SOCs). Furthermore, because ß₁ integrins are considered to play a major role in homing of blood-borne progenitor cells¹² and are essential for vascular smooth muscle adhesion, matrix assembly, and cell proliferation,^13,14 we also hypothesized that the integrin ₅ß₁ (the most highly abundant ß₁ integrin in proliferating smooth muscle cells in vivo)¹⁵ would be important in SOC adhesion.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Study Subjects
We used 6 blood samples from 5 healthy human volunteer donors (3 male and 2 female, age 26 to 38 years) according to a protocol previously approved by the institutional review board. Fresh blood was collected by venipuncture and anticoagulated in citrate phosphate dextrose solution (Baxter).

Buffy Coat Preparation and Vascular Progenitor Cell Culture
Human mononuclear cells (MNCs) were initially isolated from peripheral buffy coat blood in Histopaque-1077 followed by washing in MCDB 131 supplemented with hydrocortisone, antibiotics, and 10 ng/mL VEGF. Mononuclear cells were then resuspended in EGM-2 medium and placed on 3 wells of a 6-well plate coated with collagen type I (Becton Dickinson). At 4 weeks, subconfluent cell colonies were passaged and cells were subsequently cultured in either EGM-2 to maintain endothelial cell phenotype¹⁶ or EGM-2 supplemented with PDGF BB (50 ng/mL, R&D Systems) to facilitate smooth muscle cell differentiation. Human vascular smooth muscle cells (hVSMCs) were obtained from Clonetics, and human fibroblasts (hFBs) were obtained from ATCC. In separate experiments, CD34+ve mononuclear cells (90% purity) were selected using immunomagnetic beads and the MACS technique (Miltenyi Biotech), and these cells were similarly differentiated on collagen type I matrix, as described above.

Evaluation of Smooth Muscle Outgrowth Cell Phenotype
Morphological appearance and indirect immunofluorescence were used to define smooth muscle cell phenotype. Primary antibodies were used against CD34 (Immunotech IM 1869), smooth muscle actin (SMA), smooth muscle myosin heavy chain (MHC), and calponin (all from Dako Corp). In each immunofluorescence experiment, an isotype-matched IgG control was also used. Binding of primary antibodies to progenitor cells was detected with Alexa-Fluor 488–conjugated anti-mouse IgG (Eugene, Oreg). Antibodies to human vWF (Dako Corp, Carpenteria, Calif), VE-Cadherin (Santa Cruz Biotechnology, Santa Cruz, Calif), and CD31 (Sigma Co, St Louis, Mo) were used to label EOC, as previously described.^17,18 These markers allowed definition of cells as smooth muscle or endothelial lineage.

Western Blot Analysis
Western blotting was performed to identify vascular smooth muscle cell–specific cytoskeletal protein, VEGF receptor, and Tie-2 receptor expression in SOCs. Briefly, cells were homogenized in lysis buffer containing 50 mmol/L Tris HCl (pH 8.0), 150 mmol/L NaCl, 0.02% sodium azide, 0.1% SDS, 100 µg/mL PMSF, and 1 µg/mL aprotinin. The lysate had protein content determined by Bradford assay, and equal amounts of protein were denatured by boiling, reduced in 1 mmol/L DTT, followed by electrophoresis in 12% SDS-polyacrylamide gel. The protein was transferred to nitrocellulose and immunoblotted using monoclonal antibodies to SMA, human smooth muscle MHC, human calponin, and Flk1 (Santa Cruz Biotechnology) and polyclonal antibodies to Flt1 (R&D Systems, Minneapolis, Minn) and Tie-2 receptor (Santa Cruz Biotechnology, Santa Cruz, Calif) at dilutions of 1:500. Secondary anti-mouse, anti-rabbit, and anti-goat antibodies conjugated to horseradish peroxidase (Calbiochem, San Diego, Calif) at a 1:1000 dilution were used for detection using chemoluminescence (Supersignal, Pierce) and x-ray film exposure (Kodak). hVSMCs and hFBs were used as positive and negative control cells for smooth muscle–specific markers.

FACS Analysis
FACS was performed to identify both cell-surface and intracellular antigens in MNC, SOC, and EOC. Primary antibodies to SMA, CD31, and integrin ₅ß₁ were used with secondary detection using an FITC-conjugated antibody in each case. Isotype-matched IgG antibodies were used as a control, and the fluorescent intensity of stained cells was gated according to established methods.¹⁹

Outgrowth Cell Integrin ₅ß₁ Expression and Adhesion Assay
Integrin ₅ß₁ expression on MNC, EOC, and SOC was quantitated using FACS analysis. Integrin ₅ß₁ in EOC and SOC was also analyzed by Western blotting using cell lysates electrophoresed on a 4% to 20% gradient SDS-PAGE. Equal amounts of protein were transferred to nitrocellulose, and and ß subunits were immunodetected using a primary antibody to the human integrin ₅ß₁ (10 µg/mL, Chemicon, Temecula, Calif) and a secondary anti-mouse HRP conjugate (1:500), as described above. Equal loading of protein was confirmed by use of -tubulin antibody.

To confirm the adhesive function of surface ₅ß₁ integrin expression on each outgrowth cell type, adhesion assays on human fibronectin (10 µg/mL, Sigma) were performed.²⁰ Both EOC and SOC at a density of 1.5x10⁵ cells/well on a 6-well culture plate were allowed to adhere in basal medium (EBM-2) with 0.1% BSA in the presence or absence of a primary antibody to human integrin ₅ß₁ (10 µg/mL) or a mouse IgG control antibody at a similar concentration. Nonadherent cells were then washed off, and adherent cells were lifted with trypsin and subsequently counted with a hemocytometer. Percentage adhesion was calculated by dividing the number of adherent cells by the total number of cells plated per well.

Outgrowth Cell Proliferation Assay
Both SOC and EOC at a similar passage were seeded at a density of 5x10⁴ per well on a 24-well plate coated with collagen type I and incubated overnight with EGM-2 and 5% FCS. Similar initial seeding density was confirmed 12 hours after plating by use of a cell-titer MTS assay (Cell-Titer AQ, No. G5421, Promega).²¹ This generated a baseline seeding absorbance for both cell types. All cells were then growth arrested for 24 hours in serum-free EBM-2. Cells were released from growth arrest with addition of EGM-2 and 5% FCS, and the cell number in each well was determined by cell titer assay at 2, 4, 6, and 8 days after serum stimulation. The absorbance generated at each time point was expressed as a ratio of the initial seeding absorbance obtained for each progenitor cell type.

Statistics
All data are presented as mean±SEM. Comparison between groups was made using one-way ANOVA. P<0.05 was considered statistically significant.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Vascular Progenitor Response to Growth Factor Selection
Approximately 6 to 8 colonies per initial patient MNC sample seeded on collagen type I matrix with EGM-2 culture medium (Figure 1A) grew out over a 3-week period, at which time a mixed population existed of polygonal- and stellate-shaped cells (Figure 1B). These mixed cultures were passaged and split into 2 plates, which were subsequently grown in either EGM-2 with high levels of PDGF BB or EGM-2 alone to encourage smooth muscle cell and endothelial cell growth, respectively. The cells maintained in the PDGF BB–enriched medium became predominantly smooth muscle–appearing cells with a "hill and valley morphology" (Figure 1C) within an additional 2-week period. These SOCs grew at a rapid rate, achieving >40 population doublings over a 4-month period from the time of initial colony formation. The endothelial outgrowth cells (EOCs) exhibited a typical cobblestone morphology (Figure 1D) and grew at a slower rate, achieving 20 population doublings in the 4 months after colony formation. Similar differentiation was seen when using an initial CD34+ve mononuclear population to derive outgrowth cells.

View larger version (172K): [in this window] [in a new window]   Figure 1. Colony formation after MNC seeding on collagen-coated plates. Single outgrowth colony at week 1 (A) followed by colony of mixed cell phenotype at week 3 containing polygonal cells (open arrowheads) and spindle-shaped cells (arrows) (B). C, Confluent SOCs with "hill and valley" morphology. D, Confluent monolayer of endothelial-like outgrowth cells (EOC) with cobblestone appearance.

Immunophenotyping of Smooth Muscle Outgrowth Cells
To additionally evaluate phenotype, cells were stained using smooth muscle cell–specific antibodies. Subconfluent SOC stained positive for SMA, smooth muscle MHC, and calponin (Figure 2) on indirect immunofluorescence, whereas the starting MNC population and EOC stained negatively for all smooth muscle cell markers (Figure 2). Similarly, hVSMCs in culture stained positively, whereas hFBs stained negatively for all smooth muscle–specific markers (Figure 2). EOCs were confirmed positive for endothelial markers such as CD31, vWF, and VE-Cadherin, whereas SOC stained universally negative for all endothelial markers (Figure 3). In each case, the isotype-matched IgG control antibody stained negatively. To confirm the presence of smooth muscle–specific proteins in SOC but not in MNC or EOC, cell lysates from each cell type were run on SDS-PAGE, immunoblotted, and confirmed to have SMA, smooth muscle MHC, and calponin protein at appropriate molecular weights (Figure 4). Positive hVSMC and negative hFB controls also showed appropriate presence and absence of immunoreactivity for smooth muscle–specific markers (Figure 4).

View larger version (43K): [in this window] [in a new window]   Figure 2. Immunofluorescence of MNC, SOC, and EOC labeled with antibodies to SMA, smooth muscle MHC, and calponin. The secondary antibodies in each case were conjugated to Alexa-fluor. Cell nuclei were counterstained with Hoechst stain (blue). hVSMCs were used as a positive control and hFbs as a negative control for the SMC-specific markers.

View larger version (35K): [in this window] [in a new window]   Figure 3. Immunofluorescence of EOC and SOC labeled with antibodies to CD31, vWF, and VE cadherin. The secondary antibodies in each case were conjugated to Alexa-fluor. Cell nuclei were counterstained with Hoechst stain.

View larger version (33K): [in this window] [in a new window]   Figure 4. Western blot analysis of smooth muscle cell–specific proteins from MNC, EOC, and SOC lysates run on SDS-PAGE. SOC lysates were immunoreactive for SMA, smooth muscle MHC, and calponin at appropriate molecular weights, whereas EOC and the initial MNC population were nonimmunoreactive for all smooth muscle–specific antibodies. A positive control lysate (hVSMC) and a negative control lysate (hFb) were used to determine specificity of the antibodies. The loading control used was -tubulin.

To quantify the intensity of staining and the percentage of positive cells expressing SMA and CD31 in each population (MNC, SOC, and EOC), intracellular (SMA) and cell surface (CD31) antigens were determined by FACS. The smooth muscle–specific marker (SMA) was detected in 0% of both MNC and EOC populations, whereas 93% of SOC were positive for this marker at high intensity (Figure 5). Similarly, CD31 was detected in 0% of SOC but in 96% and 99% of MNC and EOC, with a much higher intensity of CD31 staining in the EOC compared with the MNC population (Figure 5).

View larger version (32K): [in this window] [in a new window]   Figure 5. FACS analysis of intracellular SMA and cell-surface CD31 in MNC, EOC, and SOC. The open heavy-lined histograms represent the test antibodies (anti-SMA and anti-CD31) and the filled histograms represent the isotype-matched control IgG antibodies.

Hematopoietic origin of SOC was confirmed by positive immunofluorescence staining for CD34 (Figures 6A and 6B). Furthermore, SOC lysates showed significant levels of both VEGF receptors (Flt1 and Flk1) (Figure 6C) on Western blotting, consistent with what has previously been described for endothelial outgrowth cells, whereas SOC lysates were negatively immunoreactive for the Tie-2 receptor compared with EOC (Figure 6C).

View larger version (37K): [in this window] [in a new window]   Figure 6. A, Immunofluorescence of SOC labeled with a primary CD34 antibody and secondary Cy3 conjugated antibody showing punctate surface CD34 labeling. B, An isotype-matched control IgG antibody stained negatively. C, Immunoblots of SOC and EOC lysates showing presence of Flt-1 and Flk-1 VEGF receptors in each outgrowth cell. In the case of Tie-2 receptor, EOC but not SOC lysates were positively immunoreactive. -tubulin was used as a loading control in each case.

Integrin ₅ß₁ Expression, Matrix Adhesion, and Cell Proliferation
Cell-surface integrin ₅ß₁ expression on MNC, EOC, and SOC was quantitated by FACS. SOC showed increased ₅ß₁ intensity and increased numbers of cells staining positive for this integrin compared with EOC and MNC (Figure 7). These data were confirmed by Western blotting of cell lysates, with SOC showing much higher levels of ₅ and ß₁ integrin subunit proteins compared with EOC (Figure 7). To test the functional significance of increased integrin ₅ß₁ expression on SOC compared with EOC, a fibronectin adhesion assay was performed. SOC showed an 8-fold greater adherence to fibronectin compared with EOC (P<0.001), and this effect could be significantly inhibited (P<0.01) using an ₅ß₁ antibody, whereas similar concentrations of isotype-matched mouse IgG had no such effect (Figure 7). Moreover, SOC, when released from growth arrest with serum, had a significantly (4- to 5-fold, P<0.001) increased rate of proliferation compared with EOC of similar passage and seeding density (Figure 8).

View larger version (34K): [in this window] [in a new window]   Figure 7. FACS analysis of surface expression of integrin 5ß1 on MNC (A), EOC (B), and SOC (C). D, Western blot analysis of SOC and EOC membrane lysates showing very positive immunoreactivity for integrin 5ß1 subunits in SOC compared with EOC. E, Adhesion of cultured human SOC and EOC to human fibronectin in the presence and absence of an antibody to 5ß1 integrin and mouse IgG control (mIgG). *P<0.001 compared with SOC alone (n=4 for all experiments).

View larger version (17K): [in this window] [in a new window]   Figure 8. Cell proliferation of similar passage SOC and EOC after release from growth arrest with 5% FCS. *P<0.001 compared with EOC at the same time period after growth arrest (n=3 for all experiments).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
We report here for the first time the ex vivo outgrowth culture of SOC from putative SPC in human blood. We provide several lines of evidence to demonstrate that hematopoietic mononuclear cells do indeed differentiate in culture into smooth muscle cells. First, SOC grown out from mononuclear cells showed classic smooth muscle morphology and immunophenotype but were CD34 positive, a surface marker known to be absent from adult human smooth muscle cells.^22–24 Second, no smooth muscle cell–specific markers were detected in freshly isolated mononuclear cells either by FACS, Western blotting, or immunofluorescence staining. Third, mononuclear cells cultured in the presence of VEGF rather than PDGF expanded into endothelial monolayers that were negative for smooth muscle cell–specific markers by FACS, Western blotting, and immunofluorescence. Fourth, expanded SOC showed a capacity for extended growth in culture (>40 population doublings) in contrast to adult human smooth muscle cells, which become senescent after 10 population doublings.^25,26 Together, these data make it extremely unlikely that the SOC observed in this study resulted from contaminating adult smooth muscle cells.

PDGF BB promoted adult smooth muscle cell differentiation and expansion from progenitor colonies of mixed morphological appearance in this study, whereas VEGF did not. It has previously been shown that PDGF BB is implicated in embryonic smooth muscle cell differentiation,⁵ and the present study would support a potential role for PDGF BB in differentiation of smooth muscle cells from putative progenitors in circulating blood. Indeed, whereas PDGF BB expression is tightly regulated in vivo,²⁷ it is known to be released from platelets²⁸ and is upregulated at sites of endothelial perturbation and vascular injury.²⁹ Because these sites of PDGF BB expression are precisely where vascular smooth muscle cell proliferation occurs, it is possible to speculate that interaction between PDGF BB and circulating SPC could occur at the blood-vessel wall interface.

SOCs in this study expressed both VEGF 1 and 2 receptors but not Tie-2 receptor, consistent with an angioblastic lineage distinct from EOC that has previously been described as Tie-2 receptor positive.^3,9 This nonendothelial phenotype of SOC is supported by a morphological and protein expression phenotype of these cells, which was different from EOCs grown from the same MNC pool, and by a lack of CD31, VE cadherin, vWF, and Tie-2 receptor labeling in these cells.

Integrin ₅ß₁ expression and adhesion to fibronectin were markedly increased in SOC compared with EOC in this study, the latter functional effect being significantly inhibited by ₅ß₁ integrin antibody. These data suggest that SOC rather than EOC might preferentially attach to fibronectin extracellular matrix. This integrin profile could potentially allow differentiated circulating SPC to attach to sites in vivo, where fibronectin or other ₅ß₁ adhesive matrices, such as fibrin,³⁰ are exposed to flowing blood. Because these conditions frequently exist after endothelial perturbation or plaque rupture, it is possible that fibrin clot or exposed subendothelial fibronectin in the vessel wall could serve as the soil in which circulating SPCs attach and proliferate. The proliferative capacity of SOC is supported by much higher rates of in vitro cell growth seen in SOC compared with EOC in this study. Together, these data support a paradigm for circulating SPC with the potential for differentiation, homing, and proliferation at sites rich in extracellular matrix proteins such as fibronectin.

Several in vivo animal studies have suggested that bone marrow–derived smooth muscle cells contribute to transplant arteriopathy and neointima formation after vascular injury and hyperlipidemia.^6–9 The present study, by demonstrating smooth muscle cell outgrowth from putative SPC in blood, extends this theoretical framework to human subjects. These findings may have implications for understanding what cells constitute the vasculature in adults, opening new possibilities for diagnosis and therapy of vasoproliferative disease. For instance, monitoring of these cells in blood may enable assessment of atherosclerosis progression, whereas targeting of surface integrins on these cells may inhibit homing to vascular components such as fibronectin. Finally, ex vivo expansion of these cells may have implications for cell, gene, and tissue engineering approaches to vascular disease.

	Acknowledgments

 
This work was supported by the Mayo Foundation, the Rappaport Program in Vascular Biology, and the National Institutes of Health (HL-66958 P01-NMC).

	Footnotes

 
This article originally appeared Online on August 19, 2002 (Circulation. 2002;106:r41–r46).

Received July 10, 2002; revision received July 18, 2002; accepted July 18, 2002.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993; 362: 801–809.[CrossRef][Medline] [Order article via Infotrieve]

2. Nakajima Y, Mironov V, Yamagishi T, et al. Expression of smooth muscle alpha-actin in mesenchymal cells during formation of avian endocardial cushion tissue: a role for transforming growth factor ß₃. Dev Dyn. 1997; 209: 296–309.[CrossRef][Medline] [Order article via Infotrieve]

3. Hellstrom M, Kal n M, Lindahl P, et al. Role of PDGF-B and PDGFR-ß in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development. 1999; 126: 3047–3055.[Abstract]

4. Hirschi KK, Rohovsky SA, D’Amore PA. PDGF, TGF-ß, and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate. J Cell Biol. 1998; 141: 805–814.[Abstract/Free Full Text]

5. Yamashita J, Itoh H, Hirashima M, et al. Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature. 2000; 408: 92–96.[CrossRef][Medline] [Order article via Infotrieve]

6. Shimizu K, Sugiyama S, Aikawa M, et al. Host bone-marrow cells are a source of donor intimal smooth-muscle-like cells in murine aortic transplant arteriopathy. Nat Med. 2001; 7: 738–741.[CrossRef][Medline] [Order article via Infotrieve]

7. Hillebrands JL, Klatter FA, van den Hurk BM, et al. Origin of neointimal endothelium and -actin-positive smooth muscle cells in transplant arteriosclerosis. J Clin Invest. 2001; 107: 1411–1422.[CrossRef][Medline] [Order article via Infotrieve]

8. Han CI, Campbell GR, Campbell JH. Circulating bone marrow cells can contribute to neointimal formation. J Vasc Res. 2001; 38: 113–119.[CrossRef][Medline] [Order article via Infotrieve]

9. Sata M, Saiura A, Kunisato A, et al. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med. 2002; 8: 403–409.[CrossRef][Medline] [Order article via Infotrieve]

10. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997; 275: 964–967.[Abstract/Free Full Text]

11. Shi Q, Rafii S, Wu MH, et al. Evidence for circulating bone marrow-derived endothelial cells. Blood. 1998; 92: 362–367.[Abstract/Free Full Text]

12. Ramirez M, Segovia JC, Benet I, et al. Ex vivo expansion of umbilical cord blood (UCB) CD34(+) cells alters the expression and function of ₄ß₁ and ₅ß₁ integrins. Br J Haematol. 2001; 115: 213–221.[CrossRef][Medline] [Order article via Infotrieve]

13. Yamamoto K, Yamamoto M. Cell adhesion receptors for native and denatured type I collagens and fibronectin in rabbit arterial smooth muscle cells in culture. Exp Cell Res. 1994; 214: 258–263.[CrossRef][Medline] [Order article via Infotrieve]

14. Mercurius KO, Morla AO. Inhibition of vascular smooth muscle cell growth by inhibition of fibronectin matrix assembly. Circ Res. 1998; 82: 548–556.[Abstract/Free Full Text]

15. Pickering JG, Chow LH, Li S, et al. ₅ß₁ integrin expression and luminal edge fibronectin matrix assembly by smooth muscle cells after arterial injury. Am J Pathol. 2000; 156: 453–465.[Abstract/Free Full Text]

16. Lin Y, Weisdorf DJ, Solovey A, et al. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest. 2000; 105: 71–77.[Medline] [Order article via Infotrieve]

17. Rafii S, Shapiro F, Rimarachin J, et al. Isolation and characterization of human bone marrow microvascular endothelial cells: hematopoietic progenitor cell adhesion. Blood. 1994; 84: 10–19.[Abstract/Free Full Text]

18. Sahagun G, Moore SA, Fabry Z, et al. Purification of murine endothelial cell cultures by flow cytometry using fluorescein-labeled griffonia simplicifolia agglutinin. Am J Pathol. 1989; 134: 1227–1232.[Abstract]

19. Schmid I, Uittenbogaart CH, Giorgi JV. A gentle fixation and permeabilization method for combined cell surface and intracellular staining with improved precision in DNA quantification. Cytometry. 1991; 12: 279–285.[CrossRef][Medline] [Order article via Infotrieve]

20. Davenpeck KL, Marcinkiewicz C, Wang D, et al. Regional differences in integrin expression: role of ₅ß₁ in regulating smooth muscle cell functions. Circ Res. 2001; 88: 352–358.[Abstract/Free Full Text]

21. Roehm NW, Rodgers GH, Hatfield SM, et al. An improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT. J Immunol Methods. 1991; 142: 257–265.[CrossRef][Medline] [Order article via Infotrieve]

22. Bhattacharya V, McSweeney PA, Shi Q, et al. Enhanced endothelialization and microvessel formation in polyester grafts seeded with CD34⁺ bone marrow cells. Blood. 2000; 95: 581–585.[Abstract/Free Full Text]

23. Chen YX, Nakashima Y, Tanaka K, et al. Immunohistochemical expression of vascular endothelial growth factor/vascular permeability factor in atherosclerotic intimas of human coronary arteries. Arterioscler Thromb Vasc Biol. 1999; 19: 131–139.[Abstract/Free Full Text]

24. Mofidi R, Crotty TB, McCarthy P, et al. Association between plaque instability, angiogenesis and symptomatic carotid occlusive disease. Br J Surg. 2001; 88: 945–950.[CrossRef][Medline] [Order article via Infotrieve]

25. Bonin LR, Madden K, Shera K, et al. Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque. Arterioscler Thromb Vasc Biol. 1999; 19: 575–587.[Abstract/Free Full Text]

26. Caplice NM, West MJ, Campbell GR, et al. Inhibition of human vascular smooth muscle cell growth by heparin. Lancet. 1994; 344: 97–98.[CrossRef][Medline] [Order article via Infotrieve]

27. Majesky MW, Benditt EP, Schwartz SM. Expression and developmental control of platelet-derived growth factor A-chain and B-chain/Sis genes in rat aortic smooth muscle cells. Proc Natl Acad Sci U S A. 1988; 85: 1524–1528.[Abstract/Free Full Text]

28. Bowen-Pope DF, Hart CE, Seifert RA. Sera and conditioned media contain different isoforms of platelet-derived growth factor (PDGF) which bind to different classes of PDGF receptor. J Biol Chem. 1989; 264: 2502–2508.[Abstract/Free Full Text]

29. Majesky MW, Reidy MA, Bowen-Pope DF, et al. PDGF ligand and receptor gene expression during repair of arterial injury. J Cell Biol. 1990; 111: 2149–2158.[Abstract/Free Full Text]

30. Duplaa C, Couffinhal T, Dufourcq P, et al. The integrin very late antigen-4 is expressed in human smooth muscle cell: involvement of ₄ and vascular cell adhesion molecule-1 during smooth muscle cell differentiation. Circ Res. 1997; 80: 159–169.[Abstract/Free Full Text]

This article has been cited by other articles:

				F. Zhang, S. Tsai, K. Kato, D. Yamanouchi, C. Wang, S. Rafii, B. Liu, and K. C. Kent Transforming Growth Factor-{beta} Promotes Recruitment of Bone Marrow Cells and Bone Marrow-derived Mesenchymal Stem Cells through Stimulation of MCP-1 Production in Vascular Smooth Muscle Cells J. Biol. Chem., June 26, 2009; 284(26): 17564 - 17574. [Abstract] [Full Text] [PDF]

				B. Hegner, M. Lange, A. Kusch, K. Essin, O. Sezer, E. Schulze-Lohoff, F. C. Luft, M. Gollasch, and D. Dragun mTOR Regulates Vascular Smooth Muscle Cell Differentiation From Human Bone Marrow-Derived Mesenchymal Progenitors Arterioscler. Thromb. Vasc. Biol., February 1, 2009; 29(2): 232 - 238. [Abstract] [Full Text] [PDF]

				B. De Geest The origin of intimal smooth muscle cells: are we on a steady road back to the past? Cardiovasc Res, January 1, 2009; 81(1): 7 - 8. [Full Text] [PDF]

				L. Rodriguez-Menocal, M. St-Pierre, Y. Wei, S. Khan, D. Mateu, M. Calfa, A. A. Rahnemai-Azar, G. Striker, S. M. Pham, and R. I. Vazquez-Padron The origin of post-injury neointimal cells in the rat balloon injury model Cardiovasc Res, January 1, 2009; 81(1): 46 - 53. [Abstract] [Full Text] [PDF]

				K. Satoh, Y. Fukumoto, M. Nakano, K. Sugimura, J. Nawata, J. Demachi, A. Karibe, Y. Kagaya, N. Ishii, K. Sugamura, et al. Statin ameliorates hypoxia-induced pulmonary hypertension associated with down-regulated stromal cell-derived factor-1 Cardiovasc Res, January 1, 2009; 81(1): 226 - 234. [Abstract] [Full Text] [PDF]

				J. M. Melero-Martin, M. E. De Obaldia, S.-Y. Kang, Z. A. Khan, L. Yuan, P. Oettgen, and J. Bischoff Engineering Robust and Functional Vascular Networks In Vivo With Human Adult and Cord Blood-Derived Progenitor Cells Circ. Res., July 18, 2008; 103(2): 194 - 202. [Abstract] [Full Text] [PDF]

				J. Y. Liu, H. F. Peng, and S. T. Andreadis Contractile smooth muscle cells derived from hair-follicle stem cells Cardiovasc Res, July 1, 2008; 79(1): 24 - 33. [Abstract] [Full Text] [PDF]

				M. Thill, N. V. Strunnikova, M. J. Berna, N. Gordiyenko, K. Schmid, S. W. Cousins, D. J. S. Thompson, and K. G. Csaky Late Outgrowth Endothelial Progenitor Cells in Patients with Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., June 1, 2008; 49(6): 2696 - 2708. [Abstract] [Full Text] [PDF]

				K. Kaneko, X. Li, X. Zhang, J. J. Lamberti, S. W. Jamieson, and P. A. Thistlethwaite Endothelial Expression of Bone Morphogenetic Protein Receptor Type 1a is Required for Atrioventricular Valve Formation Ann. Thorac. Surg., June 1, 2008; 85(6): 2090 - 2098. [Abstract] [Full Text] [PDF]

				Q. Xu Stem Cells and Transplant Arteriosclerosis Circ. Res., May 9, 2008; 102(9): 1011 - 1024. [Abstract] [Full Text] [PDF]

				M. Mayr, A. Zampetaki, A. Sidibe, U. Mayr, X. Yin, A. I. De Souza, Y.-L. Chung, B. Madhu, P. H. Quax, Y. Hu, et al. Proteomic and Metabolomic Analysis of Smooth Muscle Cells Derived From the Arterial Media and Adventitial Progenitors of Apolipoprotein E-Deficient Mice Circ. Res., May 9, 2008; 102(9): 1046 - 1056. [Abstract] [Full Text] [PDF]

				T. J. Bunch, C. S. Rihal, R. J. Gumina, L. Cooper, and N. M. Caplice Progression of Nonculprit Plaque Stenosis Following Successful Percutaneous Intervention Angiology, May 1, 2008; 59(2): 236 - 239. [Abstract] [PDF]

				D. Chen, J. M. Abrahams, L. M. Smith, J. H. McVey, R. I. Lechler, and A. Dorling Regenerative repair after endoluminal injury in mice with specific antagonism of protease activated receptors on CD34+ vascular progenitors Blood, April 15, 2008; 111(8): 4155 - 4164. [Abstract] [Full Text] [PDF]

				K. Hobo, T. Shimizu, H. Sekine, T. Shin'oka, T. Okano, and H. Kurosawa Therapeutic Angiogenesis Using Tissue Engineered Human Smooth Muscle Cell Sheets Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 637 - 643. [Abstract] [Full Text] [PDF]

				H. Rienstra, C. J. Zeebregts, and J.-L. Hillebrands The Source of Neointimal Cells in Vein Grafts: Does the Origin Matter? Am. J. Pathol., March 1, 2008; 172(3): 566 - 570. [Abstract] [Full Text] [PDF]

				J. Zoll, V. Fontaine, P. Gourdy, V. Barateau, J. Vilar, A. Leroyer, I. Lopes-Kam, Z. Mallat, J.-F. Arnal, P. Henry, et al. Role of human smooth muscle cell progenitors in atherosclerotic plaque development and composition Cardiovasc Res, February 1, 2008; 77(3): 471 - 480. [Abstract] [Full Text] [PDF]

				K. Satoh and B. C. Berk Circulating smooth muscle progenitor cells: novel players in plaque stability Cardiovasc Res, February 1, 2008; 77(3): 445 - 447. [Full Text] [PDF]

				J. Murphy, R. Summer, and A. Fine Stem Cells in Airway Smooth Muscle: State of the Art Proceedings of the ATS, January 1, 2008; 5(1): 11 - 14. [Abstract] [Full Text] [PDF]

				E. I. Chang, S. A. Loh, D. J. Ceradini, E. I. Chang, S.-e Lin, N. Bastidas, S. Aarabi, D. A. Chan, M. L. Freedman, A. J. Giaccia, et al. Age Decreases Endothelial Progenitor Cell Recruitment Through Decreases in Hypoxia-Inducible Factor 1{alpha} Stabilization During Ischemia Circulation, December 11, 2007; 116(24): 2818 - 2829. [Abstract] [Full Text] [PDF]

				E. Karshovska, A. Zernecke, G. Sevilmis, A. Millet, M. Hristov, C. D. Cohen, H. Schmid, F. Krotz, H.-Y. Sohn, V. Klauss, et al. Expression of HIF-1{alpha} in Injured Arteries Controls SDF-1{alpha} Mediated Neointima Formation in Apolipoprotein E Deficient Mice Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2540 - 2547. [Abstract] [Full Text] [PDF]

				S. Sakao, L. Taraseviciene-Stewart, C. D. Cool, Y. Tada, Y. Kasahara, K. Kurosu, N. Tanabe, Y. Takiguchi, K. Tatsumi, T. Kuriyama, et al. VEGF-R blockade causes endothelial cell apoptosis, expansion of surviving CD34+ precursor cells and transdifferentiation to smooth muscle-like and neuronal-like cells FASEB J, November 1, 2007; 21(13): 3640 - 3652. [Abstract] [Full Text] [PDF]

				R. C.M. Siow and A. T. Churchman Adventitial growth factor signalling and vascular remodelling: Potential of perivascular gene transfer from the outside-in Cardiovasc Res, September 1, 2007; 75(4): 659 - 668. [Abstract] [Full Text] [PDF]

				L. S. Ferreira, S. Gerecht, H. F. Shieh, N. Watson, M. A. Rupnick, S. M. Dallabrida, G. Vunjak-Novakovic, and R. Langer Vascular Progenitor Cells Isolated From Human Embryonic Stem Cells Give Rise to Endothelial and Smooth Muscle Like Cells and Form Vascular Networks In Vivo Circ. Res., August 3, 2007; 101(3): 286 - 294. [Abstract] [Full Text] [PDF]

				J. Y. Liu, D. D. Swartz, H. F. Peng, S. F. Gugino, J. A. Russell, and S. T. Andreadis Functional tissue-engineered blood vessels from bone marrow progenitor cells Cardiovasc Res, August 1, 2007; 75(3): 618 - 628. [Abstract] [Full Text] [PDF]

				G. Ishii, T.-K. Ito, K. Aoyagi, H. Fujimoto, H. Chiba, T. Hasebe, S. Fujii, K. Nagai, H. Sasaki, and A. Ochiai Presence of Human Circulating Progenitor Cells for Cancer Stromal Fibroblasts in the Blood of Lung Cancer Patients Stem Cells, June 1, 2007; 25(6): 1469 - 1477. [Abstract] [Full Text] [PDF]

				G. Invernici, C. Emanueli, P. Madeddu, S. Cristini, S. Gadau, A. Benetti, E. Ciusani, G. Stassi, M. Siragusa, R. Nicosia, et al. Human Fetal Aorta Contains Vascular Progenitor Cells Capable of Inducing Vasculogenesis, Angiogenesis, and Myogenesis in Vitro and in a Murine Model of Peripheral Ischemia Am. J. Pathol., June 1, 2007; 170(6): 1879 - 1892. [Abstract] [Full Text] [PDF]

				P. E. Westerweel, I. E. Hoefer, P. J. Blankestijn, P. de Bree, D. Groeneveld, O. van Oostrom, B. Braam, H. A. Koomans, and M. C. Verhaar End-stage renal disease causes an imbalance between endothelial and smooth muscle progenitor cells Am J Physiol Renal Physiol, April 1, 2007; 292(4): F1132 - F1140. [Abstract] [Full Text] [PDF]

				T. Inoue, M. Sata, Y. Hikichi, R. Sohma, D. Fukuda, T. Uchida, M. Shimizu, H. Komoda, and K. Node Mobilization of CD34-Positive Bone Marrow-Derived Cells After Coronary Stent Implantation: Impact on Restenosis Circulation, February 6, 2007; 115(5): 553 - 561. [Abstract] [Full Text] [PDF]

				M. Sahara, M. Sata, T. Morita, K. Nakamura, Y. Hirata, and R. Nagai Diverse Contribution of Bone Marrow Derived Cells to Vascular Remodeling Associated With Pulmonary Arterial Hypertension and Arterial Neointimal Formation Circulation, January 30, 2007; 115(4): 509 - 517. [Abstract] [Full Text] [PDF]

				K. Ohtani, K. Egashira, Y. Ihara, K. Nakano, K. Funakoshi, G. Zhao, M. Sata, and K. Sunagawa Angiotensin II Type 1 Receptor Blockade Attenuates In-Stent Restenosis by Inhibiting Inflammation and Progenitor Cells Hypertension, October 1, 2006; 48(4): 664 - 670. [Abstract] [Full Text] [PDF]

				C.-H. Wang, N. Anderson, S.-H. Li, P. E. Szmitko, W.-J. Cherng, P. W.M. Fedak, S. Fazel, R.-K. Li, T. M. Yau, R. D. Weisel, et al. Stem Cell Factor Deficiency Is Vasculoprotective: Unraveling a New Therapeutic Potential of Imatinib Mesylate Circ. Res., September 15, 2006; 99(6): 617 - 625. [Abstract] [Full Text] [PDF]

				L. V. Rodriguez, Z. Alfonso, R. Zhang, J. Leung, B. Wu, and L. J. Ignarro Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells PNAS, August 8, 2006; 103(32): 12167 - 12172. [Abstract] [Full Text] [PDF]

				Y. Misao, G. Takemura, M. Arai, T. Ohno, H. Onogi, T. Takahashi, S. Minatoguchi, T. Fujiwara, and H. Fujiwara Importance of recruitment of bone marrow-derived CXCR4+ cells in post-infarct cardiac repair mediated by G-CSF Cardiovasc Res, August 1, 2006; 71(3): 455 - 465. [Abstract] [Full Text] [PDF]

				H.-J. Cho, T.-Y. Kim, H.-J. Cho, K.-W. Park, S.-Y. Zhang, J.-H. Kim, S.-H. Kim, J.-Y. Hahn, H.-J. Kang, Y.-B. Park, et al. The Effect of Stem Cell Mobilization by Granulocyte-Colony Stimulating Factor on Neointimal Hyperplasia and Endothelial Healing After Vascular Injury With Bare-Metal Versus Paclitaxel-Eluting Stents J. Am. Coll. Cardiol., July 18, 2006; 48(2): 366 - 374. [Abstract] [Full Text] [PDF]

				M. Nataatmadja, J. West, and M. West Overexpression of Transforming Growth Factor-{beta} Is Associated With Increased Hyaluronan Content and Impairment of Repair in Marfan Syndrome Aortic Aneurysm Circulation, July 4, 2006; 114(1_suppl): I-371 - I-377. [Abstract] [Full Text] [PDF]

				K. Schafer, M. R. Schroeter, C. Dellas, M. Puls, M. Nitsche, E. Weiss, G. Hasenfuss, and S. V. Konstantinides Plasminogen Activator Inhibitor-1 From Bone Marrow-Derived Cells Suppresses Neointimal Formation After Vascular Injury in Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1254 - 1259. [Abstract] [Full Text] [PDF]

				S. Massberg, I. Konrad, K. Schurzinger, M. Lorenz, S. Schneider, D. Zohlnhoefer, K. Hoppe, M. Schiemann, E. Kennerknecht, S. Sauer, et al. Platelets secrete stromal cell-derived factor 1{alpha} and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo J. Exp. Med., May 15, 2006; 203(5): 1221 - 1233. [Abstract] [Full Text] [PDF]

				M. G. Frid, J. A. Brunetti, D. L. Burke, T. C. Carpenter, N. J. Davie, J. T. Reeves, M. T. Roedersheimer, N. van Rooijen, and K. R. Stenmark Hypoxia-Induced Pulmonary Vascular Remodeling Requires Recruitment of Circulating Mesenchymal Precursors of a Monocyte/Macrophage Lineage Am. J. Pathol., February 1, 2006; 168(2): 659 - 669. [Abstract] [Full Text] [PDF]

				N. Werner and G. Nickenig Influence of Cardiovascular Risk Factors on Endothelial Progenitor Cells: Limitations for Therapy? Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 257 - 266. [Abstract] [Full Text] [PDF]

				N. Chen, J. E. Hudson, P. Walczak, I. Misiuta, S. Garbuzova-Davis, L. Jiang, J. Sanchez-Ramos, P. R. Sanberg, T. Zigova, and A. E. Willing Human Umbilical Cord Blood Progenitors: The Potential of These Hematopoietic Cells to Become Neural Stem Cells, October 1, 2005; 23(10): 1560 - 1570. [Abstract] [Full Text] [PDF]

				E. Elsheikh, M. Uzunel, Z. He, J. Holgersson, G. Nowak, and S. Sumitran-Holgersson Only a specific subset of human peripheral-blood monocytes has endothelial-like functional capacity Blood, October 1, 2005; 106(7): 2347 - 2355. [Abstract] [Full Text] [PDF]

				Md. R. Abid, K. Yano, S. Guo, V. I. Patel, G. Shrikhande, K. C. Spokes, C. Ferran, and W. C. Aird Forkhead Transcription Factors Inhibit Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia J. Biol. Chem., August 19, 2005; 280(33): 29864 - 29873. [Abstract] [Full Text] [PDF]

				M. Sata, K. Tanaka, R. Nagai, G. Z. Eghbali-Fatourechi, and S. Khosla Circulating Osteoblast-Lineage Cells N. Engl. J. Med., August 18, 2005; 353(7): 737 - 738. [Full Text] [PDF]

				C. Liu, S. Wang, A. Deb, K. A. Nath, Z. S. Katusic, J. P. McConnell, and N. M. Caplice Proapoptotic, Antimigratory, Antiproliferative, and Antiangiogenic Effects of Commercial C-Reactive Protein on Various Human Endothelial Cell Types In Vitro: Implications of Contaminating Presence of Sodium Azide in Commercial Preparation Circ. Res., July 22, 2005; 97(2): 135 - 143. [Abstract] [Full Text] [PDF]

				J. I. Rotmans, J. M.M. Heyligers, H. J.M. Verhagen, E. Velema, M. M. Nagtegaal, D. P.V. de Kleijn, F. G. de Groot, E. S.G. Stroes, and G. Pasterkamp In Vivo Cell Seeding With Anti-CD34 Antibodies Successfully Accelerates Endothelialization but Stimulates Intimal Hyperplasia in Porcine Arteriovenous Expanded Polytetrafluoroethylene Grafts Circulation, July 5, 2005; 112(1): 12 - 18. [Abstract] [Full Text] [PDF]

				O. A. Ajijola, P. J. Goldschmidt-Clermont, and L. L. Satterwhite CD40 Ligand: Not Bad to the Bone (Marrow), After All Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1088 - 1090. [Full Text] [PDF]

				M. R. Hoenig, G. R. Campbell, B. E. Rolfe, and J. H. Campbell Tissue-Engineered Blood Vessels: Alternative to Autologous Grafts? Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1128 - 1134. [Abstract] [Full Text] [PDF]

				A. Zernecke, A. Schober, I. Bot, P. von Hundelshausen, E. A. Liehn, B. Mopps, M. Mericskay, P. Gierschik, E. A. Biessen, and C. Weber SDF-1{alpha}/CXCR4 Axis Is Instrumental in Neointimal Hyperplasia and Recruitment of Smooth Muscle Progenitor Cells Circ. Res., April 15, 2005; 96(7): 784 - 791. [Abstract] [Full Text] [PDF]

				D. A. Ingram, L. E. Mead, D. B. Moore, W. Woodard, A. Fenoglio, and M. C. Yoder Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells Blood, April 1, 2005; 105(7): 2783 - 2786. [Abstract] [Full Text] [PDF]

				D. Fukuda, M. Sata, K. Tanaka, and R. Nagai Potent Inhibitory Effect of Sirolimus on Circulating Vascular Progenitor Cells Circulation, February 22, 2005; 111(7): 926 - 931. [Abstract] [Full Text] [PDF]

				A. Kanematsu, S. Yamamoto, E. Iwai-Kanai, I. Kanatani, M. Imamura, R. M. Adam, Y. Tabata, and O. Ogawa Induction of Smooth Muscle Cell-Like Phenotype in Marrow-Derived Cells among Regenerating Urinary Bladder Smooth Muscle Cells Am. J. Pathol., February 1, 2005; 166(2): 565 - 573. [Abstract] [Full Text] [PDF]

				P. Religa, K. Bojakowski, M. Bojakowska, Z. Gaciong, J. Thyberg, and U. Hedin Allogenic immune response promotes the accumulation of host-derived smooth muscle cells in transplant arteriosclerosis Cardiovasc Res, February 1, 2005; 65(2): 535 - 545. [Abstract] [Full Text] [PDF]

				X. Chen, S. E. Kelemen, and M. V. Autieri Expression of granulocyte colony-stimulating factor is induced in injured rat carotid arteries and mediates vascular smooth muscle cell migration Am J Physiol Cell Physiol, January 1, 2005; 288(1): C81 - C88. [Abstract] [Full Text] [PDF]

				G. Nowak, A. Karrar, C. Holmen, S. Nava, M. Uzunel, K. Hultenby, and S. Sumitran-Holgersson Expression of Vascular Endothelial Growth Factor Receptor-2 or Tie-2 on Peripheral Blood Cells Defines Functionally Competent Cell Populations Capable of Reendothelialization Circulation, December 14, 2004; 110(24): 3699 - 3707. [Abstract] [Full Text] [PDF]

				J.-H. Choi, J. Hur, C.-H. Yoon, J.-H. Kim, C.-S. Lee, S.-W. Youn, I.-Y. Oh, C. Skurk, T. Murohara, Y.-B. Park, et al. Augmentation of Therapeutic Angiogenesis Using Genetically Modified Human Endothelial Progenitor Cells with Altered Glycogen Synthase Kinase-3{beta} Activity J. Biol. Chem., November 19, 2004; 279(47): 49430 - 49438. [Abstract] [Full Text] [PDF]

				T. He, T. E. Peterson, E. L. Holmuhamedov, A. Terzic, N. M. Caplice, L. W. Oberley, and Z. S. Katusic Human Endothelial Progenitor Cells Tolerate Oxidative Stress Due to Intrinsically High Expression of Manganese Superoxide Dismutase Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 2021 - 2027. [Abstract] [Full Text] [PDF]

				C. Weber, A. Schober, and A. Zernecke Chemokines: Key Regulators of Mononuclear Cell Recruitment in Atherosclerotic Vascular Disease Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 1997 - 2008. [Abstract] [Full Text] [PDF]

				D. A. Ingram, L. E. Mead, H. Tanaka, V. Meade, A. Fenoglio, K. Mortell, K. Pollok, M. J. Ferkowicz, D. Gilley, and M. C. Yoder Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood Blood, November 1, 2004; 104(9): 2752 - 2760. [Abstract] [Full Text] [PDF]

				A. Deb, K. A. Skelding, S. Wang, M. Reeder, D. Simper, and N. M. Caplice Integrin Profile and In Vivo Homing of Human Smooth Muscle Progenitor Cells Circulation, October 26, 2004; 110(17): 2673 - 2677. [Abstract] [Full Text] [PDF]

				R. Khurana, Z. Zhuang, S. Bhardwaj, M. Murakami, E. De Muinck, S. Yla-Herttuala, N. Ferrara, J. F. Martin, I. Zachary, and M. Simons Angiogenesis-Dependent and Independent Phases of Intimal Hyperplasia Circulation, October 19, 2004; 110(16): 2436 - 2443. [Abstract] [Full Text] [PDF]

				D. Kong, L. G. Melo, M. Gnecchi, L. Zhang, G. Mostoslavsky, C. C. Liew, R. E. Pratt, and V. J. Dzau Cytokine-Induced Mobilization of Circulating Endothelial Progenitor Cells Enhances Repair of Injured Arteries Circulation, October 5, 2004; 110(14): 2039 - 2046. [Abstract] [Full Text] [PDF]

				M. Abedin, Y. Tintut, and L. L. Demer Mesenchymal Stem Cells and the Artery Wall Circ. Res., October 1, 2004; 95(7): 671 - 676. [Abstract] [Full Text] [PDF]

				E. Sho, M. Sho, H. Nanjo, K. Kawamura, H. Masuda, and R. L. Dalman Hemodynamic Regulation of CD34+ Cell Localization and Differentiation in Experimental Aneurysms Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1916 - 1921. [Abstract] [Full Text] [PDF]

				T. He, L. A. Smith, S. Harrington, K. A. Nath, N. M. Caplice, and Z. S. Katusic Transplantation of Circulating Endothelial Progenitor Cells Restores Endothelial Function of Denuded Rabbit Carotid Arteries Stroke, October 1, 2004; 35(10): 2378 - 2384. [Abstract] [Full Text] [PDF]

				E. Tagliafico, S. Brunelli, A. Bergamaschi, L. De Angelis, R. Scardigli, D. Galli, R. Battini, P. Bianco, S. Ferrari, G. Cossu, et al. TGF{beta}/BMP activate the smooth muscle/bone differentiation programs in mesoangioblasts J. Cell Sci., September 1, 2004; 117(19): 4377 - 4388. [Abstract] [Full Text] [PDF]

				D. Fukuda, K. Shimada, A. Tanaka, T. Kawarabayashi, M. Yoshiyama, and J. Yoshikawa Circulating monocytes and late in-stent restenosis: Reply J. Am. Coll. Cardiol., August 18, 2004; 44(4): 936 - 937. [Full Text] [PDF]

				B. Hibbert, Y.-X. Chen, and E. R. O'Brien c-kit-Immunopositive vascular progenitor cells populate human coronary in-stent restenosis but not primary atherosclerotic lesions Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H518 - H524. [Abstract] [Full Text] [PDF]

				G. K. Owens, M. S. Kumar, and B. R. Wamhoff Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease Physiol Rev, July 1, 2004; 84(3): 767 - 801. [Abstract] [Full Text] [PDF]

				N. J. Davie, J. T. Crossno Jr., M. G. Frid, S. E. Hofmeister, J. T. Reeves, D. M. Hyde, T. C. Carpenter, J. A. Brunetti, I. K. McNiece, and K. R. Stenmark Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: contribution of progenitor cells Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L668 - L678. [Abstract] [Full Text] [PDF]

				S. Le Ricousse-Roussanne, V. Barateau, J.-o. Contreres, B. Boval, L. Kraus-Berthier, and G. Tobelem Ex vivo differentiated endothelial and smooth muscle cells from human cord blood progenitors home to the angiogenic tumor vasculature Cardiovasc Res, April 1, 2004; 62(1): 176 - 184. [Abstract] [Full Text] [PDF]

				D. Fukuda, K. Shimada, A. Tanaka, T. Kawarabayashi, M. Yoshiyama, and J. Yoshikawa Circulating monocytes and in-stent neointima after coronary stent implantation J. Am. Coll. Cardiol., January 7, 2004; 43(1): 18 - 23. [Abstract] [Full Text] [PDF]

				J.-B. Michel Anoikis in the Cardiovascular System: Known and Unknown Extracellular Mediators Arterioscler. Thromb. Vasc. Biol., December 1, 2003; 23(12): 2146 - 2154. [Abstract] [Full Text] [PDF]

				D. Skowasch, A. Jabs, R. Andrie, S. Dinkelbach, B. Luderitz, and G. Bauriedel Presence of bone-marrow- and neural-crest-derived cells in intimal hyperplasia at the time of clinical in-stent restenosis Cardiovasc Res, December 1, 2003; 60(3): 684 - 691. [Abstract] [Full Text] [PDF]

				A. Schober, S. Knarren, M. Lietz, E. A. Lin, and C. Weber Crucial Role of Stromal Cell-Derived Factor-1{alpha} in Neointima Formation After Vascular Injury in Apolipoprotein E-Deficient Mice Circulation, November 18, 2003; 108(20): 2491 - 2497. [Abstract] [Full Text] [PDF]

				M. Kuwana, Y. Okazaki, H. Kodama, K. Izumi, H. Yasuoka, Y. Ogawa, Y. Kawakami, and Y. Ikeda Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation J. Leukoc. Biol., November 1, 2003; 74(5): 833 - 845. [Abstract] [Full Text] [PDF]

				E. T.H. Yeh, S. Zhang, H. D. Wu, M. Korbling, J. T. Willerson, and Z. Estrov Transdifferentiation of Human Peripheral Blood CD34+-Enriched Cell Population Into Cardiomyocytes, Endothelial Cells, and Smooth Muscle Cells In Vivo Circulation, October 28, 2003; 108(17): 2070 - 2073. [Abstract] [Full Text] [PDF]

				Q. Xu, Z. Zhang, F. Davison, and Y. Hu Circulating Progenitor Cells Regenerate Endothelium of Vein Graft Atherosclerosis, Which Is Diminished in ApoE-Deficient Mice Circ. Res., October 17, 2003; 93 (8): e76 - e86. [Abstract] [Full Text] [PDF]

				R. Gulati, D. Jevremovic, T. E. Peterson, T. A. Witt, L. S. Kleppe, C. S. Mueske, A. Lerman, R. G. Vile, and R. D. Simari Autologous Culture-Modified Mononuclear Cells Confer Vascular Protection After Arterial Injury Circulation, September 23, 2003; 108(12): 1520 - 1526. [Abstract] [Full Text] [PDF]

				M. Pesce, A. Orlandi, M. G. Iachininoto, S. Straino, A. R. Torella, V. Rizzuti, G. Pompilio, G. Bonanno, G. Scambia, and M. C. Capogrossi Myoendothelial Differentiation of Human Umbilical Cord Blood-Derived Stem Cells in Ischemic Limb Tissues Circ. Res., September 5, 2003; 93 (5): e51 - e62. [Abstract] [Full Text] [PDF]

				G. Bauriedel, A. Jabs, D. Skowasch, R. Hutter, J. J. Badimon, V. Fuster, U. Welsch, and B. Luderitz Dendritic cells in neointima formation after rat carotid balloon injury: coordinated expression withanti-apoptotic Bcl-2 and HSP47 in arterial repair J. Am. Coll. Cardiol., September 3, 2003; 42(5): 930 - 938. [Abstract] [Full Text] [PDF]

				T. Takahashi and R. T. Lee Dendritic cells in neointima formation: from where did you come, and what are you doing here? J. Am. Coll. Cardiol., September 3, 2003; 42(5): 939 - 941. [Full Text] [PDF]

				M. Korbling and Z. Estrov Adult Stem Cells for Tissue Repair -- A New Therapeutic Concept? N. Engl. J. Med., August 7, 2003; 349(6): 570 - 582. [Full Text] [PDF]

				D. Simper, S. Wang, A. Deb, D. Holmes, C. McGregor, R. Frantz, S. S. Kushwaha, and N. M. Caplice Endothelial Progenitor Cells Are Decreased in Blood of Cardiac Allograft Patients With Vasculopathy and Endothelial Cells of Noncardiac Origin Are Enriched in Transplant Atherosclerosis Circulation, July 15, 2003; 108(2): 143 - 149. [Abstract] [Full Text] [PDF]

				K.-i. Hirose, H. Tomiyama, R. Okazaki, T. Arai, Y. Koji, G. Zaydun, S. Hori, and A. Yamashina Increased Pulse Wave Velocity Associated with Reduced Calcaneal Quantitative Osteo-sono Index: Possible Relationship Between Atherosclerosis and Osteopenia J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2573 - 2578. [Abstract] [Full Text] [PDF]

				A. Luttun and P. Carmeliet De novo vasculogenesis in the heart Cardiovasc Res, May 1, 2003; 58(2): 378 - 389. [Abstract] [Full Text] [PDF]

				M. Sata, K. Tanaka, R. Nagai, Y. Hu, H. Dietrich, F. Davison, M. Mayr, Q. Xu, B. Ludewig, M. Erdel, et al. Origin of Smooth Muscle Progenitor Cells: Different Conclusions From Different Models * Response Circulation, April 29, 2003; 107 (16): e106 - e107. [Full Text] [PDF]

				Y. Kashiwakura, Y. Katoh, K. Tamayose, H. Konishi, N. Takaya, S. Yuhara, M. Yamada, K. Sugimoto, and H. Daida Isolation of Bone Marrow Stromal Cell-Derived Smooth Muscle Cells by a Human SM22{alpha} Promoter: In Vitro Differentiation of Putative Smooth Muscle Progenitor Cells of Bone Marrow Circulation, April 29, 2003; 107(16): 2078 - 2081. [Abstract] [Full Text] [PDF]

				N. M. Caplice, T. J. Bunch, P. G. Stalboerger, S. Wang, D. Simper, D. V. Miller, S. J. Russell, M. R. Litzow, and W. D. Edwards Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation PNAS, April 15, 2003; 100(8): 4754 - 4759. [Abstract] [Full Text] [PDF]

				J.-L. Hillebrands, F. A. Klatter, and J. Rozing Origin of Vascular Smooth Muscle Cells and the Role of Circulating Stem Cells in Transplant Arteriosclerosis Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 380 - 387. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 106/10/1199    most recent 01.CIR.0000031525.61826.A8v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Simper, D. Articles by Caplice, N. M. Search for Related Content PubMed PubMed Citation Articles by Simper, D. Articles by Caplice, N. M. Pubmed/NCBI databases Medline Plus Health Information Stem Cells Related Collections Pathophysiology Smooth muscle proliferation and differentiation Mechanism of atherosclerosis/growth factors Other Vascular biology