Adoptive transfer of genetically modified human hematopoietic stem cells into preimmune canine fetuses

Fusayuki Omori, Carolyn Lutzko, Anthony Abrams-Ogg, Kathy Lau, Cathy Gartley, Howard Dobson, Shaherose Nanji, Christine Ruedy, Roshni Singaraja, Liheng Li, A. Keith Stewart, Stephen Kruth, Ian D. Dubé

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

To develop a surrogate model system for assaying gene transfer into human hematopoietic stem cells (HSCs) with in vivo repopulating potential, we injected human marrow cells transduced with a reporter retroviral vector in long-term marrow cultures (LTMCs), into the yolk sacs of preimmune canine fetuses. Of eight mid-gestation fetuses injected through the exteriorized uterine wall and under ultrasound guidance, seven were born alive. One puppy died in the neonatal period accidentally. The remaining six puppies are all healthy at 31 months of age. There was no evidence for graft-versus-host disease or any untoward effects of in utero adoptive transfer of transduced human LTMC cells. All puppies were chimeras. Human cells, detected by fluorescence in situ hybridization, were present in blood, declining from 38% to 0.05% between 10 and 44 weeks after birth. Corresponding numbers for marrow were from 20% to 0.05%. Human cells were also detected in assays of hematopoietic cell progenitors and in stimulated blood cultures. All six puppies were positive for the presence of proviral DNA at various time- points after birth. In three dogs, provirus was detected up to 41 weeks after birth in blood or marrow, and in one dog up to 49 weeks in blood. These data support the further development of this large-animal model system for studies of human hematopoie-sis.

Original languageEnglish (US)
Pages (from-to)242-249
Number of pages8
JournalExperimental Hematology
Volume27
Issue number2
DOIs
StatePublished - Feb 1 1999

Keywords

  • Hematopoietic stem cells
  • In utero transfer
  • Long-term marrow culture (LTMC)
  • Preimmune fetus

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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    Omori, F., Lutzko, C., Abrams-Ogg, A., Lau, K., Gartley, C., Dobson, H., Nanji, S., Ruedy, C., Singaraja, R., Li, L., Stewart, A. K., Kruth, S., & Dubé, I. D. (1999). Adoptive transfer of genetically modified human hematopoietic stem cells into preimmune canine fetuses. Experimental Hematology, 27(2), 242-249. https://doi.org/10.1016/S0301-472X(98)00043-5