IN UTERO TRANSDUCTION OF FETAL HEMATOPOIETIC STEM CELLS

Project: Research project

Description

Hematopoiesis is sustained by a population of stem cells that can both
replicate and differentiate. Pluripotent hematopoietic stem cells are the
most primitive stem cells and are central to hematopoietic development.
These cells can divide to make daughter cells or can differentiate through
a hierarchial pathway of increasingly committed stem cells to mature blood
cells. The ability of each stem cell to proliferate and differentiate is
termed its developmental potential. During fetal development hematopoietic stem cells migrate from the yolk sac
to fetal liver and ultimately to the bone marrow. The hematopoietic
progeny of these cells colonize multiple organs during fetal development
including spleen, liver, thymus, lung and brain. There is considerable
evidence to suggest that the biological properties of hematopoietic cells
resident in the yolk sac or fetal liver may differ from those in adult
animals. Some but not all previous studies have suggested that the
proliferative and self-renewal capacity of fetal hematopoietic stem cells
resident in the liver are superior to those in the medullary cavity of the
adult animal. However, due to the inability to identify stem cells or the
progeny of individual stem cells, it has not been possible to characterize
the developmental potential of individual hematopoietic stem cell clones
during normal fetal development. The general goals of this proposal are: 1) To define the developmental
potential of fetal hematopoietic stem cells resident in the fetal liver; 2)
To evaluate the cellular, organ and clonal distribution of the
hematopoietic progeny of these cells in selected tissues of neonatal and
adult animals. We will achieve these goals by introducing foreign genes in
utero into hematopoietic stem cells of rat fetuses by using retroviral
vectors. Hematopoietic stem cells are actively proliferating, and are
resident in high concentrations in the liver of midgestation rats, and are
thus an attractive target for retroviral gene transfer. We have previously
demonstrated that primitive hematopoietic precursors can be retrovirally
transduced by direct injection of provirus in utero into the liver of
midgestation rats. This unique approach to transducing hematopoietic cells
in vivo will enhance the study of fetal hematopoietic development and may
provide information relative to the potential correction of genetic
diseases affecting hematopoietic cells and selected metabolic disorders in
utero.
StatusFinished
Effective start/end date4/1/923/31/97

Funding

  • National Institutes of Health: $80,233.00
  • National Institutes of Health: $79,315.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $80,233.00

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Fetal Stem Cells
Hematopoietic Stem Cells
Stem Cells
Liver
Fetal Development
Yolk Sac
Newborn Animals
Proviruses
Pluripotent Stem Cells
Hematopoiesis
Thymus Gland
Genes
Fetus
Spleen
Bone Marrow
Lung
Injections
Brain

ASJC

  • Medicine(all)