In utero Hematopoietic Stem Cell Transplantation in Canines: Exploring the Gestational Age Window of Opportunity to Maximize Engraftment

Abstract

Objective: In utero hematopoietic stem cell transplantation (IUHSCT) is a promising therapy for a variety of congenital disorders. Our objective was to determine the optimal time in gestation for IUHSCT in a canine model. Methods: IUHSCT was performed in day 31-50 (term 63) fetal canines with CD34+ cells isolated from paternal bone marrow at doses of 0.09-3.4 × 10⁹ CD34+ cells/kg and T cells (CD3+/CD5+) from paternal blood at 0.11-1.1 × 10⁹ cells/kg. Engraftment was assayed using PCR-based chimerism analysis (SRY gene detection for female recipients, and unique microsatellite loci for both sexes). Results: Microchimerism and chimerism were present in multiple recipients across most gestational ages at transplant. Maximal engraftment was obtained in hematopoietic tissues in transplants performed at 42 days. At extremes of recipient gestational age, minimal to no engraftment was seen. Conclusion: Fetal age at the time of IUHSCT plays an important role in achieving engraftment in our canine model.