Fetal immune suppression as adjunctive therapy for in utero hematopoietic stem cell transplantation in nonhuman primates

Stem Cells
Laurence E ShieldsRobert G Andrews

Abstract

In utero hematopoietic stem cell transplantation could potentially be used to treat many genetic diseases but rarely has been successful except in severe immunodeficiency syndromes. We explored two ways to potentially increase chimerism in a nonhuman primate model: (a) fetal immune suppression at the time of transplantation and (b) postnatal donor stem cell infusion. Fetal Macaca nemestrina treated with a combination of the corticosteroid betamethasone (0.9 mg/kg) and rabbit thymoglobulin (ATG; 50 mg/kg) were given haploidentical, marrow-derived, CD34+ -enriched donor cells. Animals treated postnatally received either donor-derived T cell-depleted or CD34+ -enriched marrow cells. Chimerism was determined by traditional and real-time polymerase chain reaction from marrow, marrow progenitors, peripheral blood, and mature peripheral blood progeny. After birth, the level of chimerism in the progenitor population was higher in the immune-suppressed animals relative to controls (11.3% +/- 2.7% and 5.1% +/- 1.5%, respectively; p = .057). Chimerism remained significantly elevated in both marrow (p = .02) and fluorescence-activated cell sorted and purified CD34+ cells (p = .01) relative to control animals at > or = 14 months of age. Per...Continue Reading

References

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Citations

May 2, 2006·Stem Cells and Development·C Chang I LeeAlice F Tarantal
Jul 20, 2012·Best Practice & Research. Clinical Obstetrics & Gynaecology·Citra N MattarJerry K Y Chan
May 12, 2009·Advanced Drug Delivery Reviews·Anna M WagnerDaniel Surbek
Apr 19, 2008·Seminars in Fetal & Neonatal Medicine·Daniel SurbekAnna Wagner
Nov 24, 2007·Best Practice & Research. Clinical Obstetrics & Gynaecology·Eleonor Tiblad, Magnus Westgren
Jun 15, 2007·Ultrasound in Medicine & Biology·Joaquin Santolaya-ForgasRoman Wolf
Apr 20, 2016·Frontiers in Immunology·Hua PanMauricette Michallet
Jun 11, 2008·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Demetri MerianosAlan W Flake
Sep 1, 2016·Journal of Clinical Apheresis·Lynn D HaynesDixon B Kaufman

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