Hereditary Haemorrhagic Telangiectasia
Conditions
Keywords
hereditary haemorrhagic telangiectasia, endothelial cell
Brief summary
Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome patients are carriers of a heterozygous mutation of the activin receptor-like kinase 1 (ACVRL1), Endoglin (ENG) or Mothers against decapentaplegic homolog 4 (SMAD4) gene. HHT involves the Bone Morphogenetic Protein 9 (BMP9)/Activin receptor-Like Kinase 1 (ALK1)-endoglin signalling pathway. BMP9 is a growth factor that binds to ALK1 receptor and to endoglin its co-receptors and physiologically activates Smad signaling pathway. Endothelial cells in HHT patients display half expression of functional ALK1 receptors or endoglin co-receptors or of the transcription factor SMAD4, which should lead to effects on the functions of these cells. The identification of differences in gene expression between endothelial cells from HHT patients and healthy donors will allow the identification of new functions or new target pathways for therapy. Circulating endothelial cells are rare in the bloodstream in adults, but are present in greater quantities in cord blood.
Interventions
BIOLOGICALCord blood sampling
Collection of 2 milliliters (mL) of cord blood on an Ethylenediaminetetraacetic acid (EDTA) tube, on the day of delivery and after cutting the umbilical cord, for genetic testing
BIOLOGICALCord sampling
Collection of 20 centimeters (cm) of umbilical cord
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Newborn whose parents : * are adults * are affiliated to a social security or similar * are not subject to any legal protection measures * Newborn child with one parent who has monitored for HHT confirmed by molecular biology (carrier of a mutation of the SMAD4, ENG or ACVRL1 gene). * Consent signed by the two representatives of parental authority
Exclusion criteria
* One of the two parents opposes donating the umbilical cord blood and the umbilical cord for research * One of the two parents opposes genetic testing * Patient for whom it was not possible to obtain umbilical cord blood after delivery for technical or medical reasons.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Endothelial Colony Forming Cells (ECFC) from cord blood | up to 3 weeks after cells isolation | The primary outcome is the obtention of at least one clone of 10 000 cells from the cord blood after 3 weeks from the time of isolation. Number of viable cells is measured by Trypan blue test. |
| Number of Human Umbilical Vein Endothelial Cells(HUVEC) from cord | up to one week | For the cord, the primary outcome is the obtention of 500 000 cells after one week from the isolation. Number of viable cells is measured by Trypan blue test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| cell freezing and thawing | Through study completion, an average of 5 years. | After isolation and amplification, cells from cord or from clones from the cord blood are frozen in vials. The cells viability (50 to 70% of alive cells after thawing) is a criteria of successful experiment. |
| Gene expression quantification after RNA extraction from cells | Through study completion, an average of 5 years. | The third outcome is reached when we obtain up to 5 µg of RNA after cell seeding and stimulation with growth factors. Gene expression is measured by real-time polymerase chain reaction (RT-qPCR) and Ribonucleic acid Sequencing (RNAseq). |
Countries
France
Outcome results
None listed