Secretion of proteins and antibody fragments from transiently transfected endothelial progenitor cells

Heller, Loree C.; Thinard, Reynald; Chevalier, Melanie; Arpag, Sezgi; Yu, Jing; Greferath, Ruth; Heller, Richard; Nicolau, Claude

doi:10.1111/jcmm.15511

Cited by 10 publications

(13 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the use of transfected EPCs has been proposed as a possible treatment pathway in AD by taking advantage of their ability to home to the damaged BBB. Recently, transfected EPCs that release antibodies against Aβ and reduce its aggregation have been generated ( Heller et al, 2020 ). However, this novel therapeutic approach has not yet been tested in vivo .…”

Section: Endothelial Progenitor Cells and Their Potential Role In Alz...mentioning

confidence: 99%

Endothelial Progenitor Cells and Vascular Alterations in Alzheimer’s Disease

Custodia

Ouro

Romaus-Sanjurjo

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a neurodegenerative disease representing the most common type of dementia worldwide. The early diagnosis of AD is very difficult to achieve due to its complexity and the practically unknown etiology. Therefore, this is one of the greatest challenges in the field in order to develop an accurate therapy. Within the different etiological hypotheses proposed for AD, we will focus on the two-hit vascular hypothesis and vascular alterations occurring in the disease. According to this hypothesis, the accumulation of β-amyloid protein in the brain starts as a consequence of damage in the cerebral vasculature. Given that there are several vascular and angiogenic alterations in AD, and that endothelial progenitor cells (EPCs) play a key role in endothelial repair processes, the study of EPCs in AD may be relevant to the disease etiology and perhaps a biomarker and/or therapeutic target. This review focuses on the involvement of endothelial dysfunction in the onset and progression of AD with special emphasis on EPCs as a biomarker and potential therapeutic target.

show abstract

Section: Endothelial Progenitor Cells and Their Potential Role In Alz...mentioning

confidence: 99%

Endothelial Progenitor Cells and Vascular Alterations in Alzheimer’s Disease

Custodia

Ouro

Romaus-Sanjurjo

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…Transient transfection with anti-β-amyloid Fab encoding vector using electroporation resulted in the production and secretion of Fabs, solubilizing the β-amyloid aggregates as described by Heller, Thinard et al [21].…”

Section: Resultsmentioning

confidence: 99%

“…2). The protein sequence of the active Fab fragments allowed us to build expression vectors containing the respective Fab encoding sequences as well as the insulin gene sequence to facilitate the export of the expressed protein [21].…”

Section: Resultsmentioning

confidence: 99%

“Endothelial antibody factory” at the Blood Brain Barrier: novel approach to therapy of neurodegenerative diseases

thinard¹,

Farkas

Hałasa

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Phase III clinical trials of immunotherapies against Alzheimer’s disease have failed to hit major endpoints. Despite the high doses administered, small fractions of injected monoclonal antibodies cross the blood brain barrier (BBB), likely resulting in an antibody concentration in the brain parenchyma that is too low for a therapeutic effect. Here we report a novel approach to circumvent this obstacle. Leveraging the homing properties of endothelial progenitor cells (EPCs) to reach impaired BBB, we transfected ex vivo EPCs with vectors encoding anti-β-amyloid and anti-TDP-43 antibody fragments (Fabs). The expressed Fabs retained the ability to bind to, and extensively solubilize, β-amyloid and TDP-43 aggregates. Immunofluorescence studies showed that when injected into mice, the transfected EPCs homed to the BBB where they adhered, integrated, and expressed Fabs which localized in the brain parenchyma and perivascular space. This approach can be optimized and developed as a possible cell-based gene and immunotherapy.

show abstract

“…The expression of lncRNAs is associated with OS in cancer patients. 46 , 47 , 48 , 49 Therefore, we analyzed 19 DE lncRNAs of ceRNA in this study and found differential expression in the Myc high tumor group (n = 185) and Myc low tumor group (n = 186) using the heatmap ( Figure 6 A). Among the 19 DE lncRNAs, we screened potential prognosis-associated lncRNAs by univariate and multivariate Cox regression analyses.…”

Section: Resultsmentioning

confidence: 99%

Construction of a Myc-associated ceRNA network reveals a prognostic signature in hepatocellular carcinoma

Zhang

Shi

Liu

et al. 2021

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) remains an extremely lethal disease worldwide. High-throughput methods have revealed global transcriptome dysregulation; however, a comprehensive investigation of the complexity and behavioral characteristics of the competing endogenous RNA (ceRNA) network in HCC is lacking. In this study, we extracted the transcriptome (RNA) sequencing data of 371 HCC patients from The Cancer Genome Atlas platform. With the comparison of the high Myc expression (Myc high ) tumor and low Myc expression (Myc low ) tumor groups in HCC, we identified 1,125 differentially expressed (DE) mRNAs, 589 long non-coding RNAs (lncRNAs), and 93 microRNAs (miRNAs). DE RNAs predicted the interactions necessary to construct an associated Myc ceRNA network, including 19 DE lncRNAs, 5 miRNAs, and 72 mRNAs. We identified a significant signature (long intergenic non-protein-coding [LINC] RNA 2691 [LINC02691] and LINC02499) that effectively predicted overall survival and had protective effects. The target genes of microRNA (miR)-212-3p predicted to intersect with DE mRNAs included SEC14-like protein 2 (SEC14L2) and solute carrier family 6 member 1 (SLC6A1), which were strongly correlated with survival and prognosis. With the use of the lncRNA-miRNA-mRNA axis, we constructed a ceRNA network containing four lncRNAs (LINC02691, LINC02499, LINC01354, and NAV2 antisense RNA 4), one miRNA (miR-212-3p), and two mRNAs (SEC14L2 and SLC6A1). Overall, we successfully constructed a mutually regulated ceRNA network and identified potential precision-targeted therapies and prognostic biomarkers.

show abstract

Secretion of proteins and antibody fragments from transiently transfected endothelial progenitor cells

Cited by 10 publications

References 36 publications

Endothelial Progenitor Cells and Vascular Alterations in Alzheimer’s Disease

Endothelial Progenitor Cells and Vascular Alterations in Alzheimer’s Disease

“Endothelial antibody factory” at the Blood Brain Barrier: novel approach to therapy of neurodegenerative diseases

Construction of a Myc-associated ceRNA network reveals a prognostic signature in hepatocellular carcinoma

Contact Info

Product

Resources

About