Human diseased arteries contain cells expressing leukocytic and embryonic stem cell markers

Zulli, Anthony; Buxton, Brian F.; Merrilees, Mervyn J.; Hare, David

doi:10.1016/j.humpath.2007.09.022

Cited by 9 publications

(8 citation statements)

References 19 publications

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“…Reports of SSEA3-expressing cells within human tissues such as kidney, 18 brain 19 , and skin 10 have raised the possibility that the cell-surface expression of the SSEA3 epitope may facilitate the identification and isolation of ASC-like and/or undifferentiated cell subpopulations from adult human tissues. While SSEA3 has already been used to identify human skin-derived cells that are easier to reprogram to pluripotency 10,13 (suggesting a less differentiated state), associated with a multi-lineage differentiation potential, 11 (suggesting a multipotent or possibly pluripotent state) and correlated to the occlusion of human blood vessels 20 (suggesting a possible regeneration-associated state for blood vessels), SSEA3 has not been investigated as a cell-surface biomarker facilitating the identification and isolation of human skin cells directly associated with tissue regeneration after dermal injury. The purpose of this study was to investigate whether the SSEA3 biomarker could be used to facilitate the identification and isolation of regeneration-associated cells from adult human dermis.…”

Section: Introductionmentioning

confidence: 99%

Human Skin Cells That Express Stage-Specific Embryonic Antigen 3 Associate with Dermal Tissue Regeneration

Crespo

Awe

Pera

et al. 2012

BioResearch Open Access

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Stage-specific embryonic antigen 3 (SSEA3) is a glycosphingolipid that has previously been used to identify cells with stem cell-like, multipotent, and pluripotent characteristics. A rare subpopulation of SSEA3-expressing cells exists in the dermis of adult human skin. These SSEA3-expressing cells undergo a significant increase in cell number in response to injury, suggesting a possible role in regeneration. These SSEA3-expressing regeneration-associated (SERA) cells were derived through primary cell culture, purified by fluorescence-activated cell sorting (FACS), and characterized. Longer in vitro culture of the primary skin cells led to lower SSEA3 expression stability after FACS-based purification, suggesting that the current culture conditions may need to be optimized to permit the large-scale expansion of SERA cells. The SERA cells demonstrated a global transcriptional state that was most similar to bone marrow- and fat-derived mesenchymal stem cells (MSCs), and the highest expressing SSEA3-expressing cells co-expressed CD105 (clone 35). However, while a rare population of MSCs was observed in primary human skin cell cultures that could differentiate into adipocytes, osteoblasts, or chondrocytes, SERA cells did not possess this differentiation capacity, suggesting that there are at least two different rare subpopulations in adult human skin primary cultures. The identification, efficient purification, and large-scale expansion of these rare subpopulations (SERA cells and MSCs) from heterogeneous adult human skin primary cell cultures may have applications for future patient-specific cellular therapies.

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Section: Introductionmentioning

confidence: 99%

Human Skin Cells That Express Stage-Specific Embryonic Antigen 3 Associate with Dermal Tissue Regeneration

Crespo

Awe

Pera

et al. 2012

BioResearch Open Access

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“…We also showed that the RAS anti‐atherosclerotic factors, ACE2 and the angiotensin II type 2 receptor, co‐localize in rabbit atherosclerotic plaques (Zulli et al 2006) and that such cells also express markers of embryonic stem cells, such as Oct‐4 (Zulli et al 2007 b ). In addition, our most recent publications clearly demonstrate that human diseased vessels also express markers of embryonic stem cells (Zulli et al 2007 c ) and the RAS (Zulli et al 2007 a ), indicating that cells in diseased arteries do express markers of primitive origin or might be primitive cells that have migrated into diseased tissues.…”

Section: Discussionmentioning

confidence: 89%

Co‐localization of angiotensin‐converting enzyme 2‐, octomer‐4‐ and CD34‐positive cells in rabbit atherosclerotic plaques

Zulli

Rai

Buxton

et al. 2008

Experimental Physiology

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Angiotensin-converting enzyme 2 (ACE2) is a novel enzyme with possible implications in the treatment of blood pressure disorders. Recent evidence suggests that an upregulation of ACE2 can be stimulated by all-trans retinoic acid (at-RA); however, at-RA also affects regulation of the stem-cell marker octomer-4 (Oct-4) and thus cellular differentiation. We have previously shown that smooth muscle cells and macrophages present within rabbit atherosclerotic plaques are positive for ACE2, Oct-4 and the haematopoietic stem-cell marker CD34. Thus, to provide evidence that possible at-RA treatment could affect both plaque cellular biology (via effects on cellular differentiation) and blood pressure (via ACE2), it is vital to show that cells with atherosclerotic plaques co-express all three markers. Thus, we sought to provide evidence that a subset of cells within atherosclerotic plaques is positive for ACE2, Oct-4 and CD34. We used New Zealand White rabbits that were fed a control diet supplemented with 0.5% cholesterol plus 1% methionine for 4 weeks and then allowed to consume a normal diet for 10 weeks. Immunohistochemistry was performed by standard techniques. We report that ACE2, Oct-4 and CD34 were all present within atherosclerotic plaques. Although macrophages were positive for all three markers, spindle-shaped cells in the media did not show all three markers. The endothelium overlying normal arterial wall showed positive Oct-4 and ACE2 immunoreactivity, but CD34 immunoreactivity was patchy, indicating that such cells might not have fully differentiated. It is concluded that cells in atherosclerotic plaques express co-express ACE2, Oct-4 and CD34. Further studies aimed at establishing the effects of all-trans retinoic acid on blood pressure and atherosclerotic cell differentiation are warranted.

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“…Thus, novel animal models are necessary to help elucidate which type of stem cells is vital for the regression and stabilization of coronary artery disease. In this regard, we report that human coronary artery atherosclerotic disease contains cells expressing ESC markers [15] and now an animal model in rabbit is developed to help elucidate the role of these cells in coronary artery disease. The origin of smooth muscle cells within atherosclerotic plaques is still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…We have reported the positive identification of markers of primitive cell origin and endothelial precursor cells in human and rabbit atherosclerosis. CD34+ cells [13] and embryonic stem cell markers, octomer-4 (Oct-4), the SSEA 1, 3, and 4, TRA-1-60, and TRA-1-81 [14] have been identified 2 Journal of Angiology in rabbit atherosclerotic vessels and human diseased arteries [15]. Oct-4 is a transcription factor, and its downregulation is believed to trigger the differentiation of the undifferentiated cell [16].…”

Section: Introductionmentioning

confidence: 99%

Fibrous Cap Smooth Muscle Cells in Atherosclerotic Coronary Arteries Do Not Express Pluripotent Stem Cell Markers

Sullivan

Zulli

2013

Journal of Angiology

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Rupture of the coronary artery fibrous cap is a common cause of myocardial infarction, and bone marrow derived cells could play a role in preventing plaque rupture. It is currently unknown whether smooth muscle cells within coronary artery fibrous cap formation are of mature phenotype. Objective. To characterize cells expressing bone marrow stem cells of embryonic type (ESC) markers in coronary artery fibrous cap formation. Design. New Zealand White rabbits were fed a diet supplemented with 0.5% cholesterol + 1% methionine + 5% peanut oil for 4 weeks and then a normal diet for 9 weeks. The left main coronary artery was excised from the heart, processed for paraffin and immunohistochemistry was performed by standard techniques. Results. Oct-4, SSEA 1, 3, and 4 were all present within in atherosclerotic plaque core, codistributed with RAM-11, and were sparingly found in the fibrous cap, but TRA-1-60 and TRA-1-81 positive cells were scarce. Core but not fibrous cap smooth muscle (SMC actin+) cells also showed codistribution with ESC markers. Conclusions. These results suggest that smooth muscle cells present in the fibrous cap do not express ESC markers, indicative of a mature cell.

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Human diseased arteries contain cells expressing leukocytic and embryonic stem cell markers

Cited by 9 publications

References 19 publications

Human Skin Cells That Express Stage-Specific Embryonic Antigen 3 Associate with Dermal Tissue Regeneration

Human Skin Cells That Express Stage-Specific Embryonic Antigen 3 Associate with Dermal Tissue Regeneration

Co‐localization of angiotensin‐converting enzyme 2‐, octomer‐4‐ and CD34‐positive cells in rabbit atherosclerotic plaques

Fibrous Cap Smooth Muscle Cells in Atherosclerotic Coronary Arteries Do Not Express Pluripotent Stem Cell Markers

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