Genotype Expression and Phenotype of Endothelial Cells, Carrying an ACVRL1, ENG or SMAD4 Mutation, in Response to BMP9 for the Identification of New Therapeutic Targets in Hereditary Haemorrhagic Telangiectasia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 3
- 主要终点
- Number of Endothelial Colony Forming Cells (ECFC) from cord blood
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Newborns with a parent with HHT disease
16 newborns with one parent suffering HHT disease and carrying a mutation in the ACVRL1, ENG or SMAD4 gene will be included in this study.
干预措施: Cord blood sampling (Biological)
Newborns with a parent with HHT disease
16 newborns with one parent suffering HHT disease and carrying a mutation in the ACVRL1, ENG or SMAD4 gene will be included in this study.
干预措施: Cord sampling (Biological)
结局指标
主要结局
Number of Endothelial Colony Forming Cells (ECFC) from cord blood
时间窗: 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
时间窗: 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.
次要结局
- cell freezing and thawing(Through study completion, an average of 5 years.)
- Gene expression quantification after RNA extraction from cells(Through study completion, an average of 5 years.)