RT Journal Article
T1 Searching for a cell-based therapeutic tool for haemophilia A within the embryonic/foetal liver and the aorta-gonads-mesonephros region
A1 Serrano, Luis
A1 Cañete, Ana
A1 García Leal, Tamara
A1 Tomás Gallardo, Laura
A1 Flores, Ana
A1 Torre, Paz de la
A1 Liras, Antonio
A1 Sánchez, María José
AB The development of new strategies based on cell therapy approaches to correct haemophilia A (HA) requires further insights into new cell populations capable of producing coagulation factor VIII (FVIII) and presenting stable engraftment potential. The major producers of FVIII in the adult are liver sinusoidal endothelial cells (LSECs) and in a lesser degree bone marrowderived cells, both of which have been shown to ameliorate the bleeding phenotype in adult HA mice after transplantation. We have previously shown that cells from the foetal liver (FL) and the aorta-gonads-mesonephros (AGM) haematopoietic locations possess higher LSEC engraftment potential in newborn mice compared with adult-derived LSECs, constituting likely therapeutic targets for the treatment of HA in neonates. However, less is known about the production of FVIII in embryonic locations. Quantitative polymerase chain reaction and Western blot analysis were performed to assess the relative level of FVIII production in different embryonic tissues and at various developmental stages, identifying the FL and AGM region from day 12 (E12) as prominent sources of FVIII. Furthermore, FL-derived VEcadþCD45- Lyve1þ/ endothelial/endothelial progenitor cells, presenting vascular engraftment potential, produced high levels of F8 ribonucleic acid compared with CD45þ blood progenitors or Dlk1þ hepatoblasts. In addition, we show that the E11 AGM explant cultures expanded cells with LSEC repopulation activity, instrumental to further understand signals for in vitro generation of LSECs. Taking into account the capacity for FVIII expression, culture expansion and newborn engraftment potential, these results support the use of cells with foetal characteristics for correction of FVIII deficiency in young individuals.
PB Thieme Publishing
SN 0340-6245
YR 2018
FD 2018-08
LK https://hdl.handle.net/20.500.14352/13482
UL https://hdl.handle.net/20.500.14352/13482
LA eng
NO Ministerio de Educación y Ciencia (MEC)
NO Junta de Andalucia
NO Instituto de Salud Carlos III (ISCIII)
NO Asociación andaluza de Hemofilia (ASANHEMO)
DS Docta Complutense
RD 8 abr 2025