Does telomerase reverse transcriptase induce functional de-differentiation of human endothelial cells?

Baumer, Yvonne; Funk, Dorothee; Schlosshauer, Bürkhard

doi:10.1007/s00018-010-0349-z

Cited by 12 publications

(12 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, mutant CDK4-expressing HCEnCs lost the crucial corneal endothelial cell morphology and tight junction formation, thus bringing into question their usefulness as a model system to study HCEnCs. In contrast, human telomerase reverse transcriptase (hTERT) expression has been shown to be effective in extending the life span of various cell types, with minimal impact on cell physiology and differentiation state; however, the role of hTERT in immortalization of HCEnCs has not been explored in the past [12], [13].…”

Section: Introductionmentioning

confidence: 99%

Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers

et al. 2012

View full text Add to dashboard Cite

Human corneal endothelial cells (HCEnCs) form a monolayer of hexagonal cells whose main function is to maintain corneal clarity by regulating corneal hydration. HCEnCs are derived from neural crest and are arrested in the post-mitotic state. Thus cell loss due to aging or corneal endothelial disorders leads to corneal edema and blindness–the leading indication for corneal transplantation. Here we show the existence of morphologically distinct subpopulations of HCEnCs that are interspersed among primary cells and exhibit enhanced self-renewal competence and lack of phenotypic signs of cellular senescence. Colonies of these uniform and hexagonal HCEnCs (HCEnC-21) were selectively isolated and demonstrated high proliferative potential that was dependent on endogenous upregulation of telomerase and cyclin D/CDK4. Further transduction of HCEnC-21 with telomerase yielded a highly proliferative corneal endothelial cell line (HCEnT-21T) that was devoid of oncogenic transformation and retained critical corneal endothelial cell characteristics and functionality. This study will significantly impact the fields of corneal cell biology and regenerative medicine.

show abstract

Section: Introductionmentioning

confidence: 99%

Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Primary human umbilical vein endothelial cells (HUVECs; PromoCell, Heidelberg, Germany) were cultured in EC growth medium (ECGM) with supplement mix (both PromoCell), as described previously (Baumer et al ., ). BOSC23 were grown in Dulbecco's modified Eagle's medium (DMEM; Life Technologies, Karlsruhe, Germany).…”

Section: Methodsmentioning

confidence: 97%

Towards a biofunctionalized vascular prosthesis: immune cell trapping via a growth factor receptor

Liebler

Fritz²,

Thompson³

et al. 2016

J Tissue Eng Regen Med

Self Cite

View full text Add to dashboard Cite

To improve the clinical performance of vascular prostheses, which is inacceptably low for implants with small diameters (< 6 mm), biofunctionalization of synthetic implants by endothelialization has become a major, although still unreached, aim. In order to be able to recruit native endothelial progenitor cells (EPCs) to luminal implant surfaces from the blood stream, we generated monoclonal antibodies against the EPC-specific vascular endothelial growth factor receptor 2 (VEGFR-2). Employing the very efficient genetic immunization strategy, > 10 000 hybridoma clones were generated. Screening with various deletion mutants of VEGFR-2, 49 highly-specific monoclonal antibodies (mAbs) covering all seven Ig domains of VEGFR-2 were selected. mAb 9H10 was characterized in detail. Once immobilized on synthetic surfaces, mAb 9H10 allowed, within min, nearly 100-fold enrichment of VEGFR-2-expressing cells under continuous flow conditions. Cell trapping was cell-type specific and essentially not affected by competing VEGFR-2-negative cells. To exclude that the antibody would adversely modify receptor responses, four different in vitro assays were employed. Cell proliferation, angiogenic tube formation, acetylated low-density lipoprotein uptake and VEGFR-2 phosphorylation remained unaffected, suggesting that the antibody did not interfere with the receptor functioning of human umbilical vascular endothelial cells. The molecular and cellular characteristics make the selected monoclonal antibody a very promising tool for the biofunctionalization of vascular implants. Copyright © 2016 John Wiley & Sons, Ltd.

show abstract

“…The colonized microslides were kept at 37 °C and 5% CO 2 for 2 h (CD34 + cells) or 30 min (HEK cells). Subsequent procedures were carried out as described previously [29].…”

Section: Methodsmentioning

confidence: 99%

The recombinant bifunctional protein αCD133–GPVI promotes repair of the infarcted myocardium in mice

Baumer

Leder²,

Ziegler³

et al. 2012

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Summary. Background: Bone‐marrow‐derived progenitor cells are important in myocardial repair mechanisms following prolonged ischemia. Cell‐based therapy of diseased myocardium is limited by a low level of tissue engraftment. Objectives: The aim of this study was the development of the bifunctional protein αCD133–glycoprotein (GP)VI as an effective treatment for supporting vascular and myocardial repair mechanisms. Results: We have generated and characterized a bifunctional molecule (αCD133–GPVI) that binds both to the subendothelium of the injured microvasculature and to CD133+ progenitor cells with high affinity. αCD133–GPVI enhances progenitor cell adhesion to extracellular matrix proteins and differentiation into mature endothelial cells. In vivo studies showed that αCD133–GPVI favors adhesion of circulating progenitor cells to the injured vessel wall (intravital microscopy). Also, treatment of mice undergoing experimental myocardial infarction with αCD133–GPVI‐labeled progenitor cells reduces infarction size and preserves myocardial function. Conclusions: The bifunctional trapping protein αCD133–GPVI represents a novel and promising therapeutic option for limiting heart failure of the ischemic myocardium.

show abstract

Does telomerase reverse transcriptase induce functional de-differentiation of human endothelial cells?

Cited by 12 publications

References 64 publications

Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers

Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers

Towards a biofunctionalized vascular prosthesis: immune cell trapping via a growth factor receptor

The recombinant bifunctional protein αCD133–GPVI promotes repair of the infarcted myocardium in mice

Contact Info

Product

Resources

About