The use of stem/progenitor cells for therapeutic application is restricted by the limited understanding of their behaviour during homeostasis and transplantation. Fetal progenitors/stem cells present unique characteristics compared to adult-derived counterpart cells, including stronger repopulation. Investigation on cells with fetal characteristics constitutes an interesting topic in stem cell research. Our work is focused on hematopoietic and vascular progenitors from the fetal liver using the mouse as a model system.
1-Fetal versus adult hemato/vascular progenitors.
2-Notch and hematopoietic stem cells during development
3-Cell-based therapeutic models using fetal hemato/vascular progenitors: Hemophilia A.
1- Fetal versus adult hemato/vascular progenitors. We have identified a novel fetal hemato/vascular progenitor population characterized by the high vascular engraftment behaviour compared to adult counterpart cells. Also, time and location of emergence during development was determined together with the establishment of an organ culture system for progenitor cell expansion. These studies provide with a framework to further understand the signals involved in progenitor cell generation, proliferation and engraftment activities.
2- Notch and hematopoietic stem cells during development. We study the differential engraftment behaviour of fetal versus adult hematopoietic stem cells (HSCs) in response to Notch activation by using cells isolated from SCL-NIC transgenic mice. Results from these studies can have potential implications for the design of treatments targeting distinct HSC types in blood diseases.
3- Cell-based therapeutic models using fetal hemato/vascular progenitors: Hemophilia A. We further pursue applications of fetal hemato/vascular progenitors for the development of cell-based therapeutic models, in particular for the treatment at newborn stages. One line of research focuses on pediatric hemophilia A (HA), a disease presenting a hemato/vascular endothelial dysfunction for the production of coagulation factor FVIII. We have determined that FVIII is expressed from early stages of development and in the fetal liver-derived hemato/vascular progenitors. Correction of the F8 mutant mice phenotype by transplantation of progenitor cells is currently followed.
Using different technical approaches including reporter transgenic lines for stem cell isolation and cell lineage tracing, FACS, image analysis, cell culture and transplantation assays, we aim to decipher properties of fetal stem/progenitor cells at the cellular and molecular levels with the long-term goal of better understanding their role in maintenance of homeostasis and improve their use in therapeutic applications.