title: Sheep CD34+ amniotic fluid cells have hematopoietic potential and engraft after autologous in utero transplantation.
abstract: Unmatched allogeneic in utero stem cell transplantation (IUSCT) produces poor engraftment unless the fetus has congenital immunodeficiency, probably because of maternal and fetal immune responses to injected cells. We studied the functional hematopoietic potential of transduced green fluorescent protein (GFP+) sheep amniotic fluid (AF) stem cells, before and after autologous IUSCT. CD34+ cells were selected from first trimester sheep AF, transduced overnight, and injected intravenously into NOD-SCID-gamma (NSG) mice. At 3 months, primary recipient bone marrow (BM) was injected into secondary NSG recipients. GFP+ cells were detected in the hematopoietic organs and peripheral blood of primary and secondary recipients at 3 months. Autologous IUSCT (transduced GFP+CD34+AF) was performed in fetal sheep. Six months postnatally, lamb BM was injected into secondary NSG recipients. GFP+ cells were detected in the peripheral blood of primary and secondary recipients. This confirms the hematopoietic potential of AF stem cells supporting the concept of autologous IUSCT to treat congenital hematopoietic disease.
authors.affiliation: Stem Cells and Regenerative Medicine Section, Institute of Child Health, University College London, London, United Kingdom; Prenatal Cell and Gene Therapy Group, Institute for Women's Health, University College London, London, United Kingdom; Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: S W Steven
authors.initials: SW
authors.lastname: Shaw
authors.forename: Michael P
authors.initials: MP
authors.lastname: Blundell
authors.forename: Caterina
authors.initials: C
authors.lastname: Pipino
authors.forename: Panicos
authors.initials: P
authors.lastname: Shangaris
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Maghsoudlou
authors.forename: Durrgah L
authors.initials: DL
authors.lastname: Ramachandra
authors.forename: Fanos
authors.initials: F
authors.lastname: Georgiades
authors.forename: Michael
authors.initials: M
authors.lastname: Boyd
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Porada
authors.forename: Graça
authors.initials: G
authors.lastname: Almeida-Porada
authors.forename: Po-Jen
authors.initials: PJ
authors.lastname: Cheng
authors.forename: Anna L
authors.initials: AL
authors.lastname: David
authors.forename: Paolo
authors.initials: P
authors.lastname: de Coppi
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis*; D064987:Cell- and Tissue-Based Therapy; D005260:Female; D005333:Fetus / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011247:Pregnancy; D012756:Sheep; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34
keywords: Amniotic fluid stem cells; Autologous transplantation; Cell therapy; Sheep CD34