In utero transplantation of wild-type fetal liver cells rescues factor X-deficient mice from fatal neonatal bleeding diatheses

Elliot Rosen, I. Cornelissen, Z. Liang, A. Zollman, M. Casad, J. Roahrig, M. Suckow, F. J. Castellino

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Factor X (FX)-deficient embryos suffer partial embryonic lethality with approximately 30% of the embryos arresting at midgestation. The remaining animals survive to term but die perinatally mainly from abdominal or intracranial hemorrhage. We have rescued FX-deficient mice by transplanting fetal liver cells from FX+/+, Rosa26 fetuses into midgestation embryos derived from FX+/- heterozygous crosses. FX-/- embryos were born at the expected frequency and approximately 50% of the FX-/- neonates survived longer than 4 months. FX-/- embryos receiving saline injections that survived to term died perinatally similar to untreated FXdeficient mice. The plasma levels of FX in the rescued 16-week-old FX-/- mice were approximately 1-6% of wild-type levels. β-Galactosidase-staining cells derived from the donor Rosa26 fetal liver cells were detected in 47% of the livers of adult mice. In addition, donor-derived cells were also recovered in the bone marrow, spleen, lung, and occasionally in the brain and testis. These results suggest that in utero cell transplantation could be an effective therapeutic strategy to treat pathologies resulting from the deficiency of hepatic-expressed factors.

Original languageEnglish (US)
Pages (from-to)19-27
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume1
Issue number1
DOIs
StatePublished - Jan 2003
Externally publishedYes

Fingerprint

Factor X
Disease Susceptibility
Transplantation
Hemorrhage
Liver
Embryonic Structures
Galactosidases
Intracranial Hemorrhages
Cell Transplantation
Testis
Fetus
Spleen
Bone Marrow
Pathology
Staining and Labeling
Lung
Injections

Keywords

  • Cellular transplantation
  • Coagulation
  • Factor X
  • Hepatocyte

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

In utero transplantation of wild-type fetal liver cells rescues factor X-deficient mice from fatal neonatal bleeding diatheses. / Rosen, Elliot; Cornelissen, I.; Liang, Z.; Zollman, A.; Casad, M.; Roahrig, J.; Suckow, M.; Castellino, F. J.

In: Journal of Thrombosis and Haemostasis, Vol. 1, No. 1, 01.2003, p. 19-27.

Research output: Contribution to journalArticle

Rosen, Elliot ; Cornelissen, I. ; Liang, Z. ; Zollman, A. ; Casad, M. ; Roahrig, J. ; Suckow, M. ; Castellino, F. J. / In utero transplantation of wild-type fetal liver cells rescues factor X-deficient mice from fatal neonatal bleeding diatheses. In: Journal of Thrombosis and Haemostasis. 2003 ; Vol. 1, No. 1. pp. 19-27.
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