The Intravenous Route of Injection Optimizes Engraftment and Survival in the Murine Model of In Utero Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Matthew M BoeligWilliam H Peranteau

Abstract

In utero hematopoietic cell transplantation (IUHCT) has the potential to treat a number of congenital hematologic disorders. Clinical application is limited by low levels of donor engraftment. Techniques that optimize donor cell delivery to the fetal liver (FL), the hematopoietic organ at the time of IUHCT, have the potential to enhance engraftment and the clinical success of IUHCT. We compared the 3 clinically applicable routes of injection (intravenous [i.v.], intraperitoneal [i.p.], and intrahepatic [i.h.]) and assessed short- and long-term donor cell engraftment and fetal survival in the murine model of IUHCT. We hypothesized that the i.v. route would promote direct donor cell homing to the FL, resulting in increased engraftment and allowing for larger injectate volumes without increased fetal mortality. We demonstrate that the i.v. route results in (1) rapid diffuse donor cell population of the FL compared with delayed diffuse engraftment after the i.p. and i.h. routes; (2) higher FL and spleen engraftment at early prenatal time points; (3) enhanced stable long-term peripheral blood donor cell engraftment; and (4) improved survival at higher injectate volumes, allowing for higher donor cell doses and increased long-term en...Continue Reading

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Citations

Jul 20, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·John S RileyWilliam H Peranteau
Dec 6, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jerry K Y ChanCitra N Z Mattar
Oct 26, 2016·American Journal of Respiratory Cell and Molecular Biology·Deepthi Alapati, Edward E Morrisey
Oct 10, 2018·Nature Medicine·Avery C RossidisWilliam H Peranteau
Jun 10, 2017·Stem Cells International·Neeladri Chowdhury, Atsushi Asakura
Feb 12, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Karthikeyan KandasamyCitra N Z Mattar
Feb 2, 2021·Science Advances·Rachel S RileyMichael J Mitchell
Jul 15, 2021·Nature Communications·Sourav K BoseWilliam H Peranteau
Jun 18, 2017·Seminars in Fetal & Neonatal Medicine·Russell WittWilliam H Peranteau

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